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All Journal Majalah Kedokteran Bandung Althea Medical Journal Jurnal Farmasi Klinik Indonesia Journal of Medicine and Health Majalah Patologi Indonesia
Bethy S. Hernowo
Departement of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung
Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Public Health

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PERBEDAAN EKSPRESI VASCULAR ENDOTHELIAL GROWTH FACTOR DAN EKSPRESI TISSUE FACTOR BERDASARKAN RESPONS TERAPI KEMORADIASI CISPLATIN PADA PENDERITA KARSINOMA NASOFARING STADIUM LANJUT Hendarsih, Een; Oehadian, Amaylia; Sumantri, Rachmat; Supandiman, Iman; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 47, No 1 (2015)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Vascular endothelial growth factor (VEGF) merupakan faktor angiogenik yang berperan dalam angiogenesis tumor. Tissue factor (TF) merupakan inisiator utama pembekuan darah dan merangsang protein yang mengatur angiogenesis. Penelitian bertujuan mengetahui perbedaan ekspresi VEGF dengan ekspresi TF pada penderita KNF stadium lanjut berdasarkan respons terapi kemoradiasi. Dilakukan penelitian kohort prospektif pada penderita KNF stadium III, IVa, dan IVb berdasarkan AJCC edisi ke-7 tahun 2010. Ekspresi TF dan VEGF diperiksa dengan imunohistokimia dan respons kemoradioterapi dievaluasi dengan memakai Response Evaluation Criteria in Solid Tumours (RECIST) revisi versi 1.1 tahun 2009. Analisis statistik yang digunakan adalah Uji eksak Fisher. Selama penelitian Oktober 2012?Oktober 2013 didapatkan 35 penderita KNF yang memenuhi kriteria inklusi dan 5 orang dikeluarkan dari penelitian. Pada kelompok respons didapatkan 17 dari 23 penderita ekspresi VEGF ? 25%; 6 dari 23 penderita ekspresi VEGF <25%; 16 dari 23 penderita ekspresi TF ? 33%; 7 dari 23 penderita ekspresi TF <33% (p=1,000) serta pada kelompok tidak respons 5 dari 27 penderita ekspresi VEGF ?25%; 2 dari 7 penderita ekspresi VEGF <25%; 4 dari 7 penderita ekspresi TF ? 33%; 3 dari 7 penderita ekspresi TF <33% (p=0,657). Simpulan, tidak terdapat perbedaan ekspresi VEGF dengan ekspresi TF pada penderita KNF stadium lanjut berdasarkan respons terapi kemoradiasi. [MKB. 2015;47(1):49?54]Kata kunci: Karsinoma nasofaring, respons kemoradiasi, tissue factor, vascular endothelial growth factorDifferences between Vascular Endothelial Growth Factor Expression and Tissue Factor Expression Based on Cisplatin Chemoradiation Therapy Response in Advanced Stage Nasopharyngeal CancerVascular endothelial growth factor (VEGF) is a proangiogenic factor involved in the angiogenesis of NPC. Tissue factor (TF), the main initiator of blood coagulation, also signals protein that regulates angiogenesis. This study  analyzed the differences between VEGF expression and TF expression in tumor tissue based on chemoradiation therapy response. Prospective cohort study was performed in NPC patients stage III, IVa and IVb according to the AJCC VII staging system. TF expression and VEGF expression were measured by immunohistochemistry, and chemoradiotherapy responses was evaluated by RECIST version 1.1 2009. Statistical analysis was performed using Fisher Exact test. From October 2012 to October 2013, 35 NPC patients were eligible for this study and 5 patients were excluded. In response group, there were 73.9% patients with VEGF expression ?25%, 26.1% patients with VEGF expression <25%; 69.6% patients with TF expression ?33%, 30.4% patients with TF expression <33% (p=1,000) and in no response group, there were 71,4% patients with VEGF expression ? 25%; 28.6% patients with VEGF expression <25%, 57.1% patients with TF expression  ?33%, 42.9% patients with TF expression <33% (p=0.657). In conclusion, there are differences between VEGF expression and TF expression based on the chemoradiation therapy response, but they are not significantly different. [MKB. 2015;47(1):49?54]Key words: Nasopharyngeal carcinoma, chemoradiation response, tissue factor, vascular endothelial growth factor DOI: 10.15395/mkb.v47n1.397   
Hubungan Imunoekspresi CD34 dengan Gradasi dan Stadium (Duke) pada Adenokarsinoma Kolorektal Yulianti, Herry; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Karsinoma kolorektal umum terjadi di Eropa Barat Laut dan Amerika Utara, tetapi rendah di Afrika, Asia, dan Amerika Selatan. Di Indonesia, karsinoma kolorektal merupakan masalah kesehatan masyarakat dan merupakan tiga penyakit kanker terbanyak. Angiogenesis adalah pertumbuhan dan proliferasi pembuluh darah baru dari pembuluh darah yang sudah ada. Secara imuno histokimia, mikrovaskular dapat diidentifikasi dengan menggunakanmonoklonal cluster of differentiation (CD34) antibodi. Pada beberapa penelitian, microvascular density (MVD) berhubungan dengan gradasi histologi, stadium, metastasis, dan prognosis tumor. Tujuan penelitian ini untuk mengetahui hubungan ekspresi CD34 dengan gradasi dan stadium (klasifikasi Duke) pada karsinoma kolorektal. Metode penelitian adalah cross sectional terhadap 40 kasus adenokarsinoma kolorektal yang berasal dari Departemen Patologi Anatomi Rumah Sakit Dr. Hasan Sadikin Bandung-Fakultas Kedokteran Universitas Padjadjaran tahun 2004–2005. Potongan blok parafin dari jaringan kolorektal karsinoma diwarnai dengan hematoksilin eosin untuk evaluasi histologi dan imunohistokimia menggunakan monoclonal CD34 antibody. Penghitungan MVD yang imunoreaktif dilakukan di bawah mikroskop cahaya dengan pembesaran 400x, dihitung rata-rata pada 5 tempat daerah neovaskularisasi yang paling padat. Hasil penelitian menunjukkan hubungan yang signifikan MVD dengan stadium (p<0,01) dan tidak ada hubungan yang signifikan antara MVD dan gradasi (p<0,05). Simpulan, hubungan MVD dengan kedalaman invasi dan metastasis ke kelenjar limfe yang dinilai dengan klasifikasi Duke dan CD34 dapat digunakan untuk memprediksi prognosis, memperkirakan kemungkinan metastasis melalui pembuluh darah, dan memprediksi respons terhadap terapi antiangiogenik. [MKB. 2013;45(4):240–4]Kata kunci: Adenokarsinoma kolorektal, CD34, gradasi, klasifikasi DukeCorrelation between CD34 Immunoexpression and Colorectal Adenocarcinoma Grade and Stage (Duke) Carcinoma colorectal is commonly found in Nortwest Europe and North America, but not frequently found in Africa, Asia and South America. Colorectal cancer (CRC) is a public health problem in Indonesia and currently ranks among the three most common cancers. Angiogenesis is the growth and proliferation of new blood vessels from existing vasculature. Microvessels were identified immunohistochemically using monoclonal cluster of differentiation (CD34) antibody. Several studies have noted that microvascular density (MVD) correlates with stage of disease, histological grade, metastasis, and prognosis in cancers. The aim of this study was to explore the relation between CD34 immunoexpresion and grade and stage (Duke classification) in colorectal adenocarcinoma. This is a cross sectional study with 40 colorectal carcinoma cases from Department of Pathology Anatomy, Dr. Hasan Sadikin General Hospital/Faculty of Medicine, Universitas Padjadjaran Bandung during 2004−2005. A section from paraffin embedded tissue of colorectal carcinoma was stained with hematoxylin eosin for histological and immunohistochemical evaluations using monoclonal CD34 antibody. Microvascular density was counted in five tumor areas with most intensive neovascularization using 400x field light microscopy. A significant correlation was found between the MVD and stage (p<0.01) while no significant relationship found between MVD and different grade (p<0.05). In conclusion, correlations are found between MVD with tumor invation depth and lymph node metastases determined by the Duke’ staging system and CD34 can be used to predict prognosis, possibility of hematogenous metastases and responses to antiangiogenic therapy. [MKB. 2013;45(4):240–4]Key words: Adenocarcinoma colorectal, CD34, Duke clasification, grade DOI: http://dx.doi.org/10.15395/mkb.v45n4.171
Ekspresi Protein B-RAF Mutan pada Karsinoma Tiroid Papilifer yang Bermetastasis ke Kelenjar Getah Bening Regional Achmad, Dimyati; Sebastian, Jeremy; Hernowo, Bethy S.; Rizki, Kiki A.
Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

AbstrakKarsinoma tiroid papilifer (KTP) dapat tumbuh progresif dan sekitar 33−61% kasus secara klinis telah metastasis ke kelenjar getah bening (KGB) regional pada saat diagnosis ditegakkan. Mutasi gen B-RAF dihubungkan dengan sifat biologis progresivitas KTP. Mutasi gen B-RAF akan mengkode protein B-RAF mutan yang bertindak sebagai regulator sentral pada jalur mytogen activated-pathway kinase (MAPK) dalam proses proliferasi dan dediferensiasi. Mutasi gen B-RAF dapat diidentifikasi pada tingkat deoxyribosenucleic acid (DNA), ribonucleic acid (RNA), dan protein. Masih terdapat kontroversi antara hubungan mutasi B-RAF dan metastasis KGB regional. Tujuan penelitian ini untuk mengetahui hubungan protein B-RAF mutan dengan metastasis ke KGB regional pada KTP. Penelitian ini merupakan penelitian observasional rancangan kuantitatif, studi kasus kontrol berpasangan. Penelitian dilakukan di Subbagian Bedah Onkologi, Kepala dan Leher, Departemen Ilmu Bedah dan Patologi Anatomi Fakultas Kedokteran Universitas Padjadjaran/ Rumah Sakit Dr. Hasan Sadikin Bandung. Sampel penelitian terdiri atas 38 kasus KTP dengan metastasis dan 38 kasus kontrol tanpa metastasis ke KGB regional yang dirawat di Rumah Sakit Dr. Hasan Sadikin Bandung pada periode Januari 2003−Desember 2010 dan dipilih berdasarkan proses matching. Masing-masing kelompok diperiksa B-RAF mutan dengan metode imunohistokimia. Hubungan antara tiap variabel bebas dan variabel tergantung diuji menggunakan analisis bivariat Uji McNemar.Hasil penelitian menunjukkan protein B-RAF mutan memiliki hubungan bermakna (p=0,023) dengan metastasis ke KGB regional pada KTP. Terdapat protein B-RAF mutan pada KTP mempunyai risiko untuk metastasis ke KGB regional sebesar 5,92 kali dibandingkan dengan tanpa mutasi B-RAF. Penelitian ini juga menunjukkan prevalensi B-RAF mutan sebesar 65,8% (32 kelompok kasus dan 18 kelompok kontrol). Simpulan, protein B-RAF mutan memiliki hubungan dengan metastasis ke KGB regional pada KTP. [MKB. 2013;45(4):245–50]Kata kunci: Imunohistokimia, karsinoma tiroid papilifer, metastasis ke KGB regional, mutasi B-RAFMutant B-RAF Protein Expression in Regional Lymph Node Metastasized Papillary Thyroid CarcinomaPapillary thyroid carcinoma (PTC) can become progressive and in about 33−61% of cases it has metastasized to regional lymph nodes at diagnosis. Mutation of B-RAF gene correlated with the biological characteristic of lymph node progressivity. Mutation of B-RAF will encode mutant B-RAF protein which acts as the central regulator on mytogen activated-pathway kinase (MAPK) pathway in terms of proliferation and dedifferentiation processes. B-RAF gene mutation can be identified at deoxyribosenucleic acid (DNA), ribonucleic acid (RNA) and protein levels. There are still controversies in corelation between B-RAF mutation and regional lymph node metastasis. The purpose of this study was to discover the correlation between mutant B-RAF protein and regional lymph node metastasis on PTC. This is a quantitative observational paired case-control study. The study was conducted at the Surgical Oncology, Head and Neck Division Departement of Surgery and Pathology Anatomy Departement, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung in April 2011–January 2012. The sample consisted of 38 PTC cases with metastasis and 38 control cases without regional lymph node metastasis treated in Dr. Hasan Sadikin Hospital between January 2003–December 2010 which have been selected based on the matching process. Each group was examined using the immunohistochemistry method. Correlation between each dependent and non-dependent variables were tested using McNemar bivariate analysis. The results showed that mutant B-RAF protein have a significant correlation (p=0.023) with lymph node metastasis in PTC. The risk of metastasis in B-RAF mutant group was 5.92 times higher than without mutation. This study also showed that from 76 PTC cases studied, the prevalence of mutant B-RAF was about 65.8% (32 in cases and 18 in control group). In conclusion, there is a correlation between mutant B-RAF protein and regional lymph node metastasis in papillary thyroid carcinoma. [MKB. 2013;45(4):245–50]Key words: B-RAF mutation, immunohystochemistry, papillary thyroid carcinoma, regional lymph node metastasis DOI: http://dx.doi.org/10.15395/mkb.v45n4.200
Hubungan BRAF V600E dan EGFR dengan Metastasis ke Kelenjar Getah Bening pada Adenokarsinoma Kolorektal Ariyanni, Fenny; Hassan, Abdul Hadi; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 47, No 3 (2015)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Adenokarsinoma kolorektal adalah tumor ganas epitel kolorektal yang berdiferensiasi kelenjar. Metastasis ke kelenjar getah bening sangat memengaruhi prognosis dan penatalaksanaan penderita karsinoma kolorektal. Penelitian ini untuk mengetahui hubungan BRAF V600E dan EGFR dengan metastasis ke kelenjar getah bening. Disain penelitian potong lintang analisis kategorik tidak berpasangan terhadap kasus adenokarsinoma kolorektal yang dipilih secara konsekutif dari blok parafin massa tumor yang dilakukan pemeriksaan imunohistokimia BRAF V600E dan EGFR di Departemen Patologi Anatomi Fakultas Kedokteran Universitas Padjadjaran/RSUP Dr. Hasan Sadikin Bandung pada bulan Februari sampai Juni 2014. Hasil penelitian menunjukkan tidak terdapat hubungan antara imunoekspresi BRAF V600E positif dan metastasis ke kelenjar getah bening dengan p=0,269 (uji chi-kuadrat) dan imunoekspresi EGFR yang positif dengan metastasis ke kelenjar getah bening dengan p=0,713 (uji chi-kuadrat). Imunoekspresi BRAF V600E dan EGFR yang positif tidak berhubungan dengan metastasis ke kelenjar getah bening, p=0,427 (Uji Fisher Exact). BRAF dan EGFR berperan pada epithelial mesencymal transition sehingga sel mampu bermigrasi, tetapi kemampuan migrasi ini tidak berperan pada kejadian metastasis tumor adenokarsinoma kolorektal ke kelenjar getah bening. Simpulan, imunoekspresi BRAF V600E dan EGFR pada adenokarsinoma kolorektal tidak dapat digunakan sebagai petanda agresivitas tumor adenokarsinoma kolorektal. [MKB. 2015;47(3):179–85]Kata kunci: Adenokarsinoma, BRAF V600E, EGFR, kelenjar getah bening, kolorektalAssociation of BRAF V600E and EGFR with Lymph Nodes Metastasis in Colorectal AdenocarcinomaAbstractColorectal adenocarcinoma is an epithelial malignant tumor with glandular differentiation. Lymph node metastasize affects the prognosis and management of colorectal carcinoma patients. In this study, association of BRAF V600E and EGFR with metastasis of the lymph nodes was investigated. This was a cross sectional study with unpaired categorical analysis of colorectal adenocarcinoma obtained from archival paraffin blocks from consecutively selected samples. The blocks were stained by BRAF V600E and EGFR antibody at the Department of Anatomical Pathology, Faculty of MedicineUniversitas Padjadjaran/Dr. Hasan Sadikin General Hospital during the period of February to June 2014. There was no association between positive BRAF V600E immunoexpression  and lymph node metastasis, p=0.269 (p>0.05, chi-square test). Similarly, there was no association between positive EGFR immunoexpression and lymph node metastasis, p=0.713 (p>0.05, chi-square test). Positive BRAF V600E immunoexpresion and positive EGFR immunoexpression also had no association with lymph node metastasis, p=0.427 (Fisher Exact test). BRAF and EGFR may play a role in the epithelial mesencymal transition to increase cell migration and invasion. However, in colorectal adenocarcinoma, BRAF V600E and EGFR were not associated with lymph node metastasis. In conclusions, positive BRAF V600E immunoexpression and positive EGFR immunoexpression in colorectal adenocarcinoma should not be used as markers formetastazing potentials of colorectal adenocarcinoma tumors. [MKB. 2015;47(3):179–85]Key words: Adenocarcinoma, BRAF V600E, colorectal, EGFR, lymph node DOI: 10.15395/mkb.v47n3.600
Hubungan Ekspresi Ki-67 dengan Grading Histopatologi Liposarkoma Afiati, -; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 45, No 3 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Liposarkoma merupakan salah satu tumor ganas jaringan lunak dan terbanyak ditemukan pada usia dewasa antara dekade 5 dan 7 serta jarang terjadi pada usia anak. Liposarkoma sering terjadi pada ekstremitas bawah (fosa poplitea dan paha bagian tengah), retroperitoneal, perirenal, mesenteric region, dan area bahu. Penelitian ini bersifat retrospektif dari 30 kasus liposarkoma yang diambil dari data Departemen Patologi Anatomi Rumah Sakit Dr. Hasan Sadikin Bandung yang terdiri atas 20 kasus low-grade liposarcoma dan 10 kasus high-grade liposarcoma. Penelitian dilakukan periode Februari–Mei 2011. Dilakukan pemeriksaan khusus imunohistokimia dengan menggunakan antibodi monoklonal Ki-67 yang berfungsi sebagai marker proliferasi sel, dengan tujuan melihat ekspresi Ki-67 dan apakah terdapat hubungan antara ekspresi Ki-67 dan grading histopatologi liposarkoma. Ekspresi dan intensitas warna Ki-67 pada sel tumor dibagi menjadi sangat rendah (<20% positif), rendah (20– 50% positif), sedang (50–80% positif) dan tinggi (>80% positif), sedangkan untuk intensitas warna Ki-67 dibagi menjadi lemah, sedang, dan kuat. Terdapat perbedaan yang signifikan antara ekspresi dan intensitas Ki-67 pada low-grade liposarcoma dan high-grade liposarcoma (p<0,0001). Simpulan, ekspresi Ki-67 yang tinggi dengan intensitas yang kuat hanya didapatkan pada high-grade liposarcoma yang juga berhubungan dengan progresivitas tumor. [MKB. 2013;45(3):187–91]Correlation of Ki-67 Expression with Histopathological Grading ofLiposarcomaLiposarcoma, a malignant tumor of mesenchymal origin, was one of the most common sarcomas of adults and occurs primarily in the fifth through seventh decades of life. The occurrence in children was rare. Liposarcoma were occur most frequently in the lower extremities (popliteal fossa and medial thigh), retroperitoneal, perirenal, mesenteric region and shoulder area. Retrospective study was conducted by reviewing the data from Pathology Anatomy Department Dr. Hasan Sadikin Hospital Bandung. There were 30 cases of liposarcoma, whereas lowgrade of liposarcoma 20 cases and high-grade of liposarcoma 10 cases. Research was done during February–May 2011. Immunohistochemical staining examination used monoclonal antibody Ki-67 as marker cell proliferation with the aim for looking Ki-67 expression and related with histopatholgy grade of liposarcoma. The tumor cells which showed Ki-67 expression were divided into very low (<20% positive), low (20–50% positive), moderate (50–80% positive) and high (>80% positive), whereas the intensity of Ki-67 staining was into weak, moderate and strong. There were significant differences between the Ki-67 expression and intensity level according to the histopathological types of liposarcoma (p<0.0001). In conclusions, Ki-67 expression increases with strong intensity of Ki-67 only in high-grade liposarcoma, so relates with progressivity of tumor. [MKB. 2013;45(3):187–91]DOI: http://dx.doi.org/10.15395/mkb.v45n3.149 
Hubungan Faktor Risiko, Status Instabilitas Mikrosatelit, dan Ekspresi P53 dengan Karsinogenesis Adenokarsinoma Kolorektal pada Orang Indonesia Lukman, Kiki; Yuniasari, Laely; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 44, No 4 (2012)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Berbeda dengan berbagai negara lain, karakteristik molekuler adenokarsinoma kolorektal (AKK) pada orang Indonesia di dalam kelompok usia ≤40 tahun memiliki kesamaan dengan kelompok usia >40 tahun, dan keduanya berada pada jalur karsinogenesis sporadik. Untuk mengetahui hubungan karakteristik molekuler dengan berbagai faktor risiko AKK, dilakukan penelitian potong lintang yang mempelajari hubungan berbagai faktor risiko, status instabilitas mikrosatelit (IM), dan ekspresi P53 (instabilitas kromosom=IK) pada 39 penderita AKK yang memenuhi kriteria inklusi di Rumah Sakit Dr. Hasan Sadikin Bandung dalam periode Maret 2009−Maret 2010. Diperoleh masing-masing 21 dan 18 penderita AKK laki-laki dan perempuan, serta 17 dan 22 penderita berusia >40 dan ≤40 tahun. Dilakukan pemeriksaan imunohistokimia ekspresi gen MLH1, MSH2, dan p53 untuk menentukan status IM dan IK. Hasilnya adalah penderita AKK ≤40 tahun menunjukkan 4 IM tinggi, 1 IM rendah, dan 17 IM negatif, serta 10 status P53 positif dan 12 P53 negatif. Penderita AKK >40 tahun menunjukkan 4 IM rendah, dan 13 IM negatif, yang disertai oleh 11 status P53 positif dan 6 status P53 negatif. Pada kedua kelompok tersebut tidak didapatkan perbedaan yang bermakna (p>0,05) dalam pola hubungan berbagai faktor risiko AKK dengan karakteristik molekulernya. Pola diet tinggi lemak dan protein, rendah serat, overweight, merokok, dan aktivitas fisik rendah ditemukan sebagai faktor risiko yang berperan pada kedua kelompok tersebut. Simpulan, mayoritas penderita AKK pada orang Indonesia memiliki klasifikasi molekuler berupa status IK tinggi dan status IM rendah, serta berhubungan dengan faktor risiko diet tinggi lemak dan protein, rendah serat, overweight, merokok, dan aktivitas fisik rendah. [MKB. 2012;44(4):245–52]Kata kunci: Ekspresi P53, faktor risiko, instabilitas mikro-satelit, karsinogenesis adenokarsinoma kolorektalThe Association of Risk Factors, Microsatellite Instability, and P53 Expression in the Carcinogenesis of Colorectal Adenocarcinoma among IndonesianDifferent from developed countries, molecular characteristic of colorectal adenocarcinoma (CRC) among Indonesians in the age group of ≤40 years old is mostly similar compared to the CRC of the age group of >40 years old, and both are sporadic cancers. To know the association of molecular characteristic with the risk factors of CRC, a cross sectional study was conducted to analyze the association of risk factors, microsatellite instability (MSI) and P53 expression (chromosomal Instability=CIN) status in 39 consecutive CRC patients who were eligible for this study at Dr Hasan Sadikin Hospital, from March 2009 until March 2010. They consisted of 21 male and 18 female patients. Of them, there were 17 and 22 patients with>40 and≤40 years of age, respectively. The immuno-histochemistry examinations for the expression of mutated MLH1, MSH2 and p53 genes were conducted to determine the CIN and MSI status. The results showed that the CRC ≤40 years of age had 4 MSI high, 1 MSI low, and 17 MSI negative, associated with 10 P53 positives and 12 p53 negatives. By contrast, in the CRC >40 years of age the MSI was low and negative in 4 and 13 cases, respectively. They were associated with 11 and 6 of p53 positive and negative status, respectively. Between the two groups, there were no significant differences with regards to the association pattern between the risk factors and their molecular characteristics (p>0.05). Conclusions, majority of CRC patients among Indonesian show a molecular classification of high CIN and low MSI, and is associated with risk factors of high fat and protein, low fiber dietary intake, overweight, smoking, and low physical activitis. [MKB. 2012;44(4):245–52]Key words: Carcinogenesis of colorectal carcinoma, expression of P53, microstallite instability, risk factors DOI: http://dx.doi.org/10.15395/mkb.v44n4.216
Validitas Multiplex Real Time Polymerase Chain Reaction untuk Diagnosis Limfadenitis Tuberkulosis pada Spesimen Blok Parafin Rezeki, Mike; Parwati, Ida; Hernowo, Bethy S.; Tjandrawati, Anna
Majalah Kedokteran Bandung Vol 46, No 3 (2014)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Limfadenitis tuberkulosis merupakan tuberkulosis ekstraparu yang paling sering ditemukan. Saat ini baku emas diagnosis limfadenitis tuberkulosis berdasarkan histopatologi. Pemeriksaan histopatologi tidak memberikan informasi etiologi pasti penyebab limfadenitis, padahal limfadenitis dapat disebabkan Mycobacterium tuberculosis maupun Mycobacterium non-tuberculosis yang sangat berbeda regimen terapinya. Spesimen limfadenitis tuberkulosis dalam blok parafin yang disimpan sangat bermanfaat ketika dibutuhkan pemeriksaan lanjutan.  Pemeriksaan multiplex real time polymerase chain reaction  pada  blok parafin dapat mendeteksi Mycobacterium  tuberculosis atau Mycobacterium  non-tuberculosis. Pemilihan objek penelitian dilakukan berdasarkan randomisasi sederhana. Penelitian uji diagnostik dengan  rancangan potong lintang untuk mengetahui  validitas pemeriksaan multiplex  real time polymerase chain reaction  dalam  mendiagnosis limfadenitis tuberkulosis  sebagai konfirmasi pada blok parafin dilakukan periode Juni 2012˗˗Juni 2013 di Rumah Sakit Dr. Hasan Sadikin Bandung. Objek penelitian terdiri atas 40 blok parafin limfadenitis tuberkulosis dan 22 blok parafin kelompok kontrol. Pemeriksaan multiplex real time poymerase chain reaction menggunakan primer gen sikuens sisipan IS6110 dan gen Mycobacterium protein tuberkulosis MPB64 untuk mendeteksi deoxyribonucleic acid Mycobacterium tuberculosis dan gen 16S rRNA (ribosomal ribonucleic acid) untuk mendeteksi Mycobacterium non-tuberculosis. Hasil uji validitas sensitivitas 75%, spesifisitas 77%, nilai duga positif 86,6%, nilai duga negatif 63%, dan akurasi 75,8%. Pemeriksaan multiplex real time polymerase chain reaction dapat dianjurkan untuk konfirmasi diagnosis limfadenitis tuberkulosis pada blok parafin. Simpulan: multiplex real time polymerase chain reaction  memiliki validitas sedang untuk diagnosis limfadenitis tuberkulosis pada spesimen blok parafin.Kata kunci: Deoxyribonucleic acid, limfadenitis tuberkulosis, multiplex real time polymerase chain reaction, Mycobacterium tuberculosis Validity of Multiplex Real Time Polymerase Chain Reaction for Tuberculous Lymphadenitis Diagnosis on Formalin Fixed Paraffin EmbeddedTuberculous lymphadenitis is one of the most common form of extra pulmonary tuberculous. The diagnosis of tuberculous lymphadenitis based  on  histopathology as a gold standard. Histopathology examination could not inform the etiology of lymphadenitis whether Mycobacterium tuberculosis or Mycobacterium nontuberculosis  of which  the treatment regiment is very different. The archieved specimen like formalin fixed paraffin embedded  of tuberculous lymphadenitis is useful for futher investigation. The multiplex real time polymerase chain reaction  can detect  Mycobacterium tuberculosis or Mycobacterium nontuberculosis  from formalin fixed paraffin embedded. The object of the study use simple random. The study with cross sectional design  to determine validity multiplex real time polymerase chain reaction  on tuberculous lymphadenitis from formalin fixed paraffin embedded, was done June 2012˗˗June 2013 at Dr. Hasan Sadikin Hospital Bandung. Objects  consisted  of  40  formalin fixed paraffin embedded  tuberculous lymphadenitis and  22 control group. The multiplex real time polymerase chain reaction use insertion  sequence IS6110 and Mycobacterium protein tuberculosis MPB64 gen for detect deoxyribonucleic acid Mycobacterium tuberculosis and 16S rRNA (ribosomal ribonucleic acid) gen for Mycobacterium nontuberculosis. The validity test of the Mycobacterium tuberculosis multiplex real time polymerase chain reaction with histopathology as a gold standards gave a sensitivity 75%, specificity 77%, positive predictive value 86.6%, negative predictive value 63%, and accuracy 75.8%. This examination can be used for confirmation of tuberculous lymphadenitis from formalin fixed paraffin embedded. Conclussion: multiplex real time polymerase chain reaction has intermediate validity to diagnose tuberculous lymphadentis on formalin fixed paraffin embedded.Key words: Deoxyribonucleic acid,  multiplex real time polymerase chain reaction, Mycobacterium tuberculosis DOI: 10.15395/mkb.v46n3.314
Hubungan Imunoekspresi NF-kB dengan Sinus Rokitansky Aschoff pada Kolesistitis Kronik Yulianti, Herry; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 46, No 2 (2014)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Karsinoma kandung empedu relatif jarang, tetapi merupakan penyakit yang sangat mematikan. Keganasan kandung empedu merupakan 3−4% dari seluruh lesi ganas dan menempati urutan ke-5 di antara tumor sistem pencernaan. Karsinoma kandung empedu sulit dideteksi dan didiagnosis pada stadium awal, karena biasanya gejalanya sangat sedikit atau tanpa gejala. Oleh karena itu sangat penting menegakkan diagnosis secara dini dan mendeteksi pasien risiko tinggi, termasuk batu dan riwayat kolesistitis kronik. Kolesistitis kronik merupakan peradangan kronik pada kandung empedu dan disertai kolelitiasis pada lebih dari 90% kasus. Batu empedu merupakan faktor etiologi yang penting pada karsinoma kandung empedu. Pada gambaran histopatologi kolesistitis kronik ditemukan sinus Rokitansky Aschoff. Pendekatan genetik telah membuktikan komponen inflamasi berperan dalam karsinogenesis, seperti primary inflammatory cytokines, interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, dan nuclear factor-kappaB (NF-kB). Tujuan penelitian ini untuk mengetahui hubungan imunoekspresi NF-kB dengan sinus Rokitansky Aschoff pada kolesistitis kronik. Metode penelitian adalah potong lintang terhadap 30 kasus kolesistitis kronik yang berasal dari Departemen Patologi Anatomi Rumah Sakit Dr. Hasan Sadikin Bandung/Fakultas Kedokteran Universitas Padjadjaran tahun 2010−2011. Potongan blok parafin dari jaringan kolesistitis kronik setebal 4 µm diwarnai dengan hematoksilin eosin untuk evaluasi gambaran histopatologi dan pemeriksaan imunohistokimia menggunakan polyclonal NF-kB antibody. Perhitungan sel yang imunoreaktif dilakukan di bawah mikroskop cahaya dengan pembesaran 400x, dihitung rata-rata pada 5 tempat. Hasil penelitian menunjukkan hubungan yang signifikan antara imunoekspresi NFkB dan sinus Rokitansky Aschoff (p=0,000). Simpulan, terdapat hubungan imunoekspresi NFkB dengan sinus Rokitanski Aschoff, semakin tinggi imunoekspresi NFkB semakin banyak sinus Rokitansky Aschoff. [MKB. 2014;46(2):106–11]Kata kunci: Kolesistitis kronik, NFkB, sinus Rokitansky AschoffCorrelation between Immunoexpression of NF-kB and Rokitansky Aschoff Sinuses in Chronic CholecystitisCarcinoma of the gallbladder is relatively uncommon but it is a very lethal disease. Gallbladder cancer constitutes 3−4% of all malignant lesions and ranks 5th among the digestive system tumors. Gallblader carcinoma is difficult to detect and diagnose in early stage because it usually has very slight symptoms or asymptomatic. It becomes increasingly necessary to make early diagnosis and identification of high-risk patient,as well as gallstone and history of chronic cholecystitis. Chronic cholecystitis is a chronic inflammation of gallbladder associated with cholelithiasis in more than 90% of cases. Cholelithiasis is one of the important etiological factors in carcinoma of the gallbladder. The histological examination of chronical cholecystitis shows the presence of Rokitansky Aschoff sinuses. Genetic approaches have proven that the components of inflammation such as primary inflammatory cytokines, interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6 and nuclear factor-kB (NF-kB) play the key roles in carcinogenesis. The purpose of this study was to understand the correlation between the immunoexpression of NF-kB and Rokitansky Aschoff sinuses in chronic cholecystitis. The method was cross sectional of 30 cases of chronic cholecystitis from Department of Pathology Anatomy of Dr. Hasan Sadikin General Hospital Bandung/Faculty of Medicine Universitas Padjadjaran in 2010−2011. A section from 4 µm-thick paraffin embedded tissue of chronic cholecystitis was stained with hematoxylin eosin for histopatological evaluation and immunohistochemical using polyclonal NF-kB antibody. Immunoreactive cells was counted in five tumor areas of 400x field by light microscopy. The result showed a significant correlation between the immunoexpression of NFkB and Rokitansky Aschoff sinuses (p=0.000). In conclusion, there is a correlation between immunoexpression of NFkB and Rokitansky Aschoff sinuses because as the immunoexpression of NFkB increase, more Rokitansky Aschoff sinuses will be formed. [MKB. 2014;46(2):106–11]Key words: Chronic cholecystitis, NFkB, Rokitansky Aschoff sinuses DOI:  10.15395/mkb.v46n2.282
Hubungan antara Imunoekspresi Ki-67 dan Risiko Agresivitas Tumor pada Gastrointestinal Stromal Tumor Yulianti, Herry; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 47, No 4 (2015)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Gastrointestinal stromal tumor (GIST)  merupakan tumor mesenkimal yang paling sering terjadi pada traktus gastrointestinal dan berasal dari intestinal cells of Cajal yang terdapat pada lapisan muskularis traktus gastrointestinal yang berfungsi sebagai pacemaker cell dalam mengatur motilitas intestinal. Diperkirakan insidensi GIST 3−5% dari seluruh soft tissue sarcoma. Gastrointestinal stromal tumor  dapat terjadi sepanjang traktus gastrointestinal, terbanyak pada usia pertengahan dan lebih tua, dengan usia rata-rata 50−60 tahun. Secara histologi, terdapat tiga kategori morfologi GIST, yaitu spindle cell, epitheloid, dan mixed type. Marker spesifik GIST adalah cluster of differentiation (CD117) yang mempunyai sensitivitas baik dan imunoreaktif pada 95% GIST. Ekspresi Ki-67 berhubungan dengan aktivitas proliferasi dan dapat dideteksi pada fase G1, S, G2, dan M dari siklus sel, kecuali pada fase G0. Tujuan  penelitian ini adalah mengetahui hubungan risiko agresivitas dengan aktivitas proliferasi yang diukur dengan Ki-67 pada tumor yang telah dikonfirmasi sebagai GIST dengan CD117. Penelitian ini merupakan penelitian analitik potong lintang terhadap 29 kasus GIST dari Departemen Patologi Anatomi Rumah Sakit Dr. Hasan Sadikin/Fakultas Kedokteran Universitas Padjadjaran, Rumah Sakit Santo Borromeus, Rumah Sakit Immanuel, dan Rumah Sakit Santosa Bandung pada tahun 2007−2012. Potongan blok parafin dari 55 kasus GIST diwarnai dengan hematoksilin eosin untuk evaluasi histologi dan evaluasi imunohistokimia menggunakan monoclonal CD117 antibody untuk konfirmasi diagnosis GIST. Terdapat 29 kasus  positif dengan CD117, kemudian diwarnai dengan monoclonal Ki-67 antibody. Sel yang dikategorikan positif CD117 memperlihatkan partikel coklat di dalam sitoplasma dan imunoekspresi Ki-67 dinilai dengan warna coklat pada inti sel tumor. Hasil penelitian  menunjukkan hubungan bermakna antara risiko agresivitas tumor dan imunoekspresi Ki-67 (p<0,001). Simpulan, semakin tinggi nilai ekspresi Ki-67 semakin tinggi skor risiko agresivitas sehingga pada GIST, pemeriksaan imunohistokimia Ki-67 dapat membantu menentukan apakah pasien akan mempunyai prognosis yang buruk. [MKB. 2015;47(4):231–7]Kata kunci: CD117, gastrointestinal stromal tumor, Ki-67Correlation between Ki-67 Immunoexpression and the Tumor Aggressivity Risk in Gastrointestinal Stromal TumorAbstractGastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, and arises from intestinal cells of Cajal localized in the muscular layer of the digestive tract, which functions as pacemaker cells in regulating intestinal motility. The incidence of GIST is about 3−5% of all soft tissue sarcomas. Gastrointestinal stromal tumor can occur along the gastrointestinal tract and predominantly in middle-aged and older persons, with a median age between 50 and 60 years. Histologically, there are three categories of GIST morphology such as spindle cells, epitheloid, and mixed type. A spesific marker of GIST is cluster of differentiation (CD117), which has good sensitivity and immunoreactive in 95% of GIST. The expression of Ki-67 correlates with proliferative activities and can be detected in G1, S, G2, and M phases of cell cycle but not in G0 phase. The aim of this study was to assessthe correlation between the risk of aggressive behaviors and proliferative activities as measured by Ki-67 in tumors confirmed as GIST by CD117. The method of this study was cross-sectional, performed on 29 cases of GIST from the Department of Pathology Anatomy Dr. Hasan Sadikin General Hospital/Faculty of Medicine Universitas Padjadjaran, Santo Borromeus Hospital, Immanuel Hospital, and Santosa Hospital between 2007−2012. A section from paraffin embedded tissue of 55 cases of GIST was stained with hematoxylin eosin for histological and immunohistochemical evaluations using monoclonal antibody CD117 to confirm the diagnosis of GIST. There were 29 positive cases for CD117. Further staining was performed using monoclonal antibody Ki-67. The categorized positive cells of immunoexpression of CD117 showed brown particles inside cytoplasma and the immunoexpression of Ki-67 was assessed by identification of nuclear brown staining of neoplastic cells. The result showed that there were significant correlations between the risk of tumor aggressive behaviors and immunoexpression of Ki-67 (p<0.001). In conclusion, as the immunoexpression of Ki-67 value increases, the aggressivity risk score becomes higher. Therefore, in GIST, the Ki-67 immunohistochemical analysis may help to decide which patients will have the worst prognosis. [MKB. 2015;47(4):231–7]Key words: CD117, gastrointestinal stromal tumor, Ki-67 DOI: 10.15395/mkb.v47n4.617
PERAN EKSTRAK ETANOL TOPIKAL DAUN MENGKUDU (MORINDA CITRIFOLIA L.) PADA PENYEMBUHAN LUKA DITINJAU DARI IMUNOEKSPRESI CD34 DAN KOLAGEN PADA TIKUS GALUR WISTAR Rahmayani S., Indah Puti; Maskoen, Ani Melani; Hernowo, Bethy S.
Majalah Kedokteran Bandung Vol 45, No 4 (2013)
Publisher : Faculty of Medicine, Universitas Padjadjaran

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Abstract

Luka akan menimbulkan masalah jika penanganannya kurang baik sehingga menyebabkan luka kronik. Mengkudu (Morinda citrifolia L.) merupakan tanaman khas daerah tropis termasuk Indonesia, yang buah, daun, dan akarnya sering digunakan dalam pengobatan tradisional, di antaranya untuk menyembuhkan luka. Penelitian dengan rancangan eksperimental sederhana ini bertujuan untuk mengetahui efek penggunaan ekstrak etanol daun mengkudu terhadap penyembuhan luka pada pemberian topikal, dengan melihat gambaran histopatologis yang terdiri atas sel fibroblas, infiltrasi sel inflamasi, imunoekspresi cluster of differentiation 34 (CD34), dan deposisi kolagen. Penelitian dilakukan di laboratorium Farmakologi dan Patologi Anatomi RS Dr. Hasan Sadikin Bandung pada November 2010?September 2011. Penelitian ini dilakukan pada 36 tikus dengan membuat eksisi pada punggung tikus. Kemudian tikus-tikus tersebut dibagi menjadi 2 kelompok yaitu kelompok kontrol dan perlakuan ekstrak etanol daun mengkudu topikal pada luka. Jaringan luka tiap kelompok diamati secara mikroskopis pada hari ke-3, 7, dan 14. Hasil penelitian menunjukkan penyembuhan luka kelompok perlakuan cenderung lebih baik, dilihat pada data hari ke-3, 7, dan 14 pada semua parameter. Uji statistik Mann-Whitney pada tingkat kepercayaan 95% (p<0,05) untuk jumlah fibroblas, infiltrasi sel inflamasi, imunoekspresi CD34, dan kolagen berturut-turut p=0,319; p=0,290; p=0,251; dan p=0,245. Simpulan, ekstrak etanol topikal daun mengkudu cenderung bermanfaat pada penyembuhan luka, walaupun secara statistik tidak bermakna. [MKB. 2013;45(4):226?33]Kata kunci: CD34, daun mengkudu, kolagen, penyembuhan lukaRole of Noni (Morinda citrifolia L.) Leaf Ethanolic Extract TopicalApplication on Wound Healing Examined from CD34 Immunoexpression and Collagen on Wistar RatsProblems in wound healing occurred if proper care is not given and the wound develops into a chronic wound. Noni (Morinda citrifolia L.) is one of the most common plants in tropical areas, including Indonesia, which fruit, leaves dan root are used in traditional treatment, for example wound healing. This experimental research with post test-only control group design identified the effect of topical application of noni leaves ethanol extract on wound healing by examining the histopathological appearance of fibroblas count, inflammatory cell infiltration, cluster of differentiation 34 (CD34) immunoexpression, and collagen deposition. The research was performed between November 2010 until September 2011 at the Pharmacology and Pathology Anatomy laboratories of Dr. Hasan Sadikin General Hospital Bandung. Excisions were made on each back of the rat of the 36 rats that were divided into control and test groups where the test group received topical application of noni leaves ethanol extract. The wound was examined on day 3, 7, and 14 using a light microscope. The result showed a tendency of better wound healing in the test group for all parameters based on the data on day 3, 7, and 14. Mann-Whitney Test with 95% confidence interval (p<0.05) showed that the p value for fibroblast count, inflammation cell infiltration, CD34 immunoexpression and collagen subsequently were p=0.319, p=0.290, p=0.251, and p=0.245, respectively. In conclusion, topical application of noni leaves ethanol extract has a benefit on wound healing although the results are not statistically significant. [MKB. 2013;45(4):226?33]Key words: CD34, collagen, noni leaves, wound healing DOI: http://dx.doi.org/10.15395/mkb.v45n4.169
Co-Authors - Afiati, - . Afiati, . Abdul H. Hassan, Abdul H. Abdul Hadi Hassan, Abdul Hadi Achmad Hidayat Afiati Afiati Afiati Agung Dinasti Permana Amaylia Oehadian Aminah, Hermin Aminah, Hermin Ani Melani Maskoen Anna Tjandrawati Beby S. Damayanti, Beby S. Birgitta M. Dewayani, Birgitta M. Dharmayanti Francisca Badudu, Dharmayanti Francisca Dimyati Achmad Een Hendarsih Erida, Yulie Fenny Ariyanni, Fenny Frans Ferdinal HANS-JOACHIM FREISLEBEN Hasrayati Agustina Herry Yulianti Ida Parwati Iman Supandiman Indah Puti Rahmayani S. Jeremy Sebastian Kahdar Wiradisastra Kiki A. Rizki Kiki Lukman Laely Yuniasari Mike Rezeki Mohamad Sadikin Nadytia Kusumadjayanti, Nadytia Nita Novita Nurwenda, Sartika Rachmat Sumantri Ris Kristiana, Ris Rostika Flora Septelia I. Wanandi Tri Hanggono Achmad Usman, Hermin A. Westiningrum, Retno Yenni Wisudarma, Yenni Yuniserani, Debbi