Irianiwati Widodo
Department Of Anatomical Pathology, Faculty Of Medicine, Public Health And Nursing, Universitas Gadjah Mada/Dr Sardjito Hospital, Jl. Farmako, Sekip Utara, Yogyakarta

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Molecular subtypes and clinicopathological features of breastcancer . Irianiwati
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 45, No 01 (2013)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (86.942 KB) | DOI: 10.19106/JMedScie004501201306

Abstract

Breast cancer is a heterogeneous disease with regard to morphological spectrum, clinical presentation and response to therapy. Based on immunohistochemistry detection of estrogen receptor, progesterone receptor, Her-2 status, proliferation rate and clusters of basal gene expression, breast cancers can be classified into luminal A, luminal B, basal-like/triple negative, and Her-2 positive. It was suggested that there was a close relationship between molecular subtypes and clinicopathological features of breast cancer, as they are very important to predict prognosis and therapeutic implications.  
The relationship between sirtuin 1 (SIRT1) expression and tumor size, Proliferating Cell Nuclear Antigen (PCNA) expression and histological grading in rat breast carcinoma induced by dimethylbenz()anthracene (DMBA) Novrita Padauleng; Dewajani Purnomosari; Sri Herwiyanti; . Harjadi; . Irianiwati; Sitarina Widyarini
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 45, No 04 (2013)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (2060.833 KB) | DOI: 10.19106/JMedScie004504201301

Abstract

Controversy regarding the role of SIRT1 in pathology of cancers exists and is still under debate.SIRT1 could act as either a tumor supressor or tumor promotor. This study was conducted toevaluate the relationship between SIRT1 expression and tumor size, Proliferating Cell NuclearAntigen (PCNA) expression and histological grading in rat breast carcinoma induced bydimethylbenz(á)anthracene (DMBA). Thirty female Sprague Dawley rats were randomly allocatedinto three groups with 10 rats in each group. Group 1 as negative control was just fed thestandard food. Group 2 as vehicle control was fed the standard food and corn oil. Group 3 asinduction group was fed the standard food and induced with DMBA at dose of 20 mg/kg bodyweight (BW) in corn oil twice a week for five weeks. All rats were palpated weekly to determinethe appearance, size and location of tumors. Sixteen weeks after DMBA induction rats weresacrified and histological preparations of the breast carcinoma tissue were then processed forSIRT1 and PCNA expression examination as well as histological grading. The result showed thatSIRT1 expression was significantly higher in breast carcinoma tissue compared to normal gland(26.12 vs 0.05; p = 0.004). SIRT1-positive was observed mostly in poor histological gradecarcinomas (56.2%), and it was not observed in good histological grade carcinomas. However,there was no significantly difference between SIRT1 and histological grading (p = 0.097; r =0.285). A significant correlation between SIRT1 expression and the tumor size (p =0.009; r=0.877), as well as PCNA expression (p =0.000; r =0.790) was observed. In conclusion, thereis relationship between SIRT1 expression and tumor size as well as PCNA expression in rat breastcarcinoma induced by DMBA.
Plasma DNA as a potential biomarker for breast cancer detection Dewajani Purnomosari; Ulfah Dian Indrayani; . Irianiwati; Dian Caturini Sulistyoningrum
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 4 (2016)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (545.141 KB) | DOI: 10.19106//JMedSci004804201603

Abstract

Breast cancer is a major malignancy among Indonesian women. It is often diagnosed inthe later stages of cancer, which leads to poor prognosis and survival of the patients.This study investigated plasma DNA concentration as a potential biomarker for breastcancer. The benefit of using this detection is the cost-effectiveness and the samples canbe collected from patients using non-invasive methods. Plasma samples were obtainedfrom healthy controls (n=18) and cancer patients (n=22). Each sample was split intotwo equal portions for DNA isolation using two different methods for the NaI methodand a commercially available kit (Qiagen/ QA) method. The DNA concentration wasdetermined by using a GeneQuant spectrophotometer (Pharmacia). The t-test was usedfor statistical analysis, which was performed using the SPSS 17.0 software. Compared tothe commercial method, extraction using NaI yielded higher DNA concentration, both fromsamples of healthy controls and cancer patients (p=0,008 and p=0.000, respectively).Furthermore, regardless of the isolation method used, the plasma DNA concentrationwas higher in healthy controls than in cancer cases (p=0,032 and p=0.005, for NaIand QA methods, respectively). In conclusion, isolation methods significantly affect DNAconcentrations. The plasma DNA concentration of healthy controls is significantly higherthan those of the cancer cases, suggesting that plasma DNA concentration might be apotential biomarker for breast cancer detection with less invasive sampling method thantissue biopsies.
Sinonasal or nasopharyngeal undifferentiated Carcinoma?: diagnostic pitfall and the role of Epstein-Barrvirus (EBV) and human papillomavirus(HPV) examination Wahyu Tri Widayati; Ery Kus Dwianingsih; Bustanul Ardianto; Didik Setyo Heriyanto; Sagung Rai Indrasari; Camelia Herdini; . Irianiwati
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 52, No 2 (2020)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1173.032 KB) | DOI: 10.19106/JMedSci005202202008

Abstract

Undifferentiated carcinoma of the head and neck is frequently observed in nasopharynx, however it may also occur in oropharynx, salivary gland and sinonasal. Overlapping lesions in those regionscreate difficulty in determining the origin of the tumor. Thus, it causes diagnostic pitfall not only for pathologists, but also for clinicians. A 40 yearold man, presented with nasal obstruction, epistaxis, diplopia, and headache for a yearand showed nasal cavitysinistra and nasopharynx masses on CT-scan. Lymph node enlargement was not detected. First biopsywas performed and histopathologically diagnosed as nasopharyngeal undifferentiated carcinoma(NPC), extended into nasal cavity. Chemo-radiation protocol for NPC was conducted, and showing uncomplete response. Second biopsy was done, and reviewed with the first biopsy result. Thetumourwas arranged insolid, syncytial and trabecular pattern, with vesicular nuclei, prominent nucleoli, and lack of lymphoplasmacytic infiltrat. Immunohistochemistry (IHC) analysis of p16, EBNA1 and LMP1 were negative. PCR analysis of HPV-18 was positive, while EBV detection showed negative result. General association of EBV with NPC suggests that the presence of latent EBV infection can serve as a positive marker for NPC. Therefore, in this case, the EBV negativity and strong HPV association led to diagnosis of SNUC. The distinction of sinonasal undifferentiated carcinoma (SNUC) or from NPC was important for appropriate management and therapy.
Solitary dermal cylindroma: a rare case report Wahyu Tri Widayati; . Irianiwati
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 51, No 2 (2019)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (950.357 KB) | DOI: 10.19106/JMedSci005102201910

Abstract

Dermal cylindromas are rare benign skin appendageal tumors that has two clinical presentation, solitary and multiple form. The diagnosis is unusual.However, it must be considered in clinical practice.A 51-year-old woman hadpainless nodule on right arm. Skin examinatipn revealedtwo fragmented nodules, 1x0.5x0.5cm, tan to white, and rubbery. Histopathological findings revealed a well demarcated and an unencapsulated epithelial dermal tumor, composed of numerous oval and polygonal nests molded into a "jig-saw" or "mosaic" appearance at low power. The nests of cells were composed of basaloid cells with scant cytoplasm and hyperchromatic nuclei and paler cells at the center. Nests of epithelial cells were surrounded and penetrated by a thickened band of basement membrane material that was PAS-positive. Immunohistochemistry (IHC) staining with p63 showed positive staining on basaloid cells. Langerhans dendritic cells in the surrounding nests stained positive with CD1a. Solitary dermal cylindroma occurred sporadically in patients without family history of cutaneous cylindromas.Combination of morphologic, histochemystry and immunohistochemystry staining were needed for accurate diagnosis.
The prognostic value of lymph nodes mRNA CXCL12 expression in the breast cancer idha safitri; Irianiwati Widodo; Didik Setyo Heriyanto
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 52, No 2 (2020)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (382.954 KB) | DOI: 10.19106/JMedSci005202202002

Abstract

Prognosis of breast carcinoma is influenced by age, tumor size, histological grade and type, lymph node status, as well as metastasic status. Chemokine receptor CXCR-4 with its ligand, CXCL-12, may play an important role in metastasis of breast carcinoma. However, the role of CXCL-12 mRNA as a prognostic factor and a therapeutic target of human breast cancer remains controversial. This study aimed to investigate the level of CXCL-12 mRNA expression in lymph nodes of patients with invasive ductal breast carcinoma and the difference within the prognostic factors. Axillary lymph nodes obtained from 50 cases of invasive ductal breast carcinoma, were divided into two groups, with and without lymph node metastasis. Each group consisted of 25 cases. Total RNA was extracted from formalin-fixed paraffin-embedded. The CXCL-12 mRNA expression was examined using qRT-PCR method. The mean differences between the two groups were analyzed using Mann-Whitney test. The differences between CXCL-12 mRNA expression and each prognostic factor ware analyzed using Mann-Whitney comparison test. CXCL-12 mRNA expression was significantly higher in the lymph node of patients with metastasis of breast carcinoma compared to the non-metastasis cases (p<0.01). There were significant differences between CXCL-12 mRNA expression with poorly histological grade (p=0.003), bigger primary tumor size (p=0.005) and age of ≥45 y.o (p=0.012) in the metastatic group, but there were no significant differences between both age of <45 and ≥45 y.o.This study suggests that the higher CXCL-12 mRNA expression level are associated with bigger tumor size and poor differentiation in breast cancer patient with lymph nodes metastasis 
Correlation between vascular endothelial growth factor (VEGF) expression with histopathological findings in osteosarcoma Fikar Arsyad Hakim; Yuni Artha Prabowo Putro; Yudha Mathan Sakti; Rahadyan Magetsari; Irianiwati Widodo; Ery Kus Dwianingsih
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 53, No 2 (2021)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (13.335 KB) | DOI: 10.19106/JMedSci005302202101

Abstract

Vascular endothelial growth factor (VEGF) expression is associated with malignancy progression, metastasis, and poor prognosis in many malignancies, including osteosarcoma. However, studies concerning correlations between VEGF expression and histopathological prognostic factors ofosteosarcoma are limited. This study aimed to evaluate the correlations between VEGF expression and histopathological findings in osteosarcoma’spatients.This was a cross-sectional study using formalin-fixed paraffin embedded (FFPE) samples of 32 osteosarcoma’s patients from Dr. Sardjito General Hospital, Yogyakarta. Histopathological findings of specimens were re-evaluated by two independent observers, recorded for the subtypes, invasiveness, grading, mitotic counts, and tumor infiltrating lymphocytes (TIL). Expression of VEGF was determined based on immunostaining and evaluated using immunoreactivity score (IRS).Chi-square and Spearman correlation test were used to analyze the association between variables. Range of VEGF expression score was 0 to 11, with mean 5.09. Significant negative correlation between the VEGF expression and TIL was observed (p=0.046). However, there was no significant correlations between the VEGF expression and osteosarcomas subtypes, invasion, grading or mitotic counts (p> 0.05). In conclusion, the VEGF expression is associated with TIL. Further study is needed to evaluate the roles of VEGF and lymphocytes in osteosarcoma development dan progression in order to better understand of the role of VEGF in immunotherapy of osteosarcoma.
Malignant bilateral ovarian steroid cell tumor without androgenic manifestation: an unusual finding Emilia Theresia; Bob Irsan; Ery Kus Dwianingsih; Moh Nailul Fahmi; Heru Pradjatmo; . Irianiwati
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 54, No 1 (2022)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.19106/JMedSci005401202208

Abstract

Steroid cell tumor is a rarest ovarian neoplasm, classified as a pure stromal tumor and mostly is unilateral. Even though this tumor can exhibit malignant behavior but the morphology of cells showed benign characteristics which can become a diagnosis pitfall especially in the frozen section. Moreover patient without any hormonal imbalance or virilizing signs could make the diagnosis process more difficult. Here we reported a case bilateral steroid cell tumor of the ovary in a 42 y.o. unmarried woman without any virilization or hirsutism symptoms. Abdominal ultrasonography and computed tomography (CT) scan revealed a right ovarian solid tumor accompanied by ascites and right pleural effusion. There was significantly increased of Ca 125 level (1138 U/mL) and normal level of testosterone (0.10 ng/mL). Frozen section was done from the right ovarium mass and ascites fluid, the result was benign. From the total abdominal hysterectomy and bilateral salpingo-oophorectomy tissues,  histological picture showed diffuse and nests tumor separated by thin fibrous connective tissue with small round centered nuclei, mild atypia, and abundant pale cytoplasm. Large area of necrosis was found especially in the right ovarian tumor, tumor implant to the right fallopian tube and in the uterine serous layer. Periodic acid-Schiff (PAS) stain was negative in more than half tumor cells population. Immunostaining for Melan-A and Calretinin were focally positive, with Ki-67 labeling index ± 5%, and negative for cytokeratin 7 (CK7), cytokeratin 20 (CK20) and smooth muscle actin (SMA). Based on the tumor size, necrosis area, tumor implantation, and immunohistochemistry profiles, we conclude that were malignant steroid cell tumor. Currently, the patient is undergoing postoperative recovery and planned for platinum-based chemotherapy. A careful correlation between clinical and radiological findings, as well as histopathological results, is always essential, as is amply demonstrated by this particular case.
Basal-Like Subgroup is Associated with Younger Age, Increased Expression of Androgen Receptor, and Worse Prognosis, while Non-basal-like Subtype is Associated with Higher BMI in Triple-Negative Breast Cancer Patients Ibnu Purwanto; Didik Setyo Heiyanto; Ahmad Ghozali; Irianiwati Widodo; Iwan Dwiprahasto; Teguh Aryandono; Sofia Mubarika Haryana
The Indonesian Biomedical Journal Vol 12, No 4 (2020)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v12i4.1289

Abstract

BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogenous disease which differ in characteristic, treatment response and prognosis. We aim to perform in-depth analysis on the clinicopathologic feature and the prognostic value of basal-like and non-basal-like TNBC patients in an Indonesian tertiary hospital.METHODS: We retrospectively included patients diagnosed with TNBC between 2014-2017. Clinical variables were collected from medical record. Expression of epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), p53 mutant and androgen receptor (AR) were examined by using immunohistochemistry (IHC).RESULTS: We included 67 subjects, 67.1% were basal-like and the remaining 32.9% were non-basal-like, with mean age of 51 years old, 59.7% subjects had BMI <25 and 40.3% subjects had BMI ≥25; 16.4%, 65.7%, and 17.9% subjects presented with early stage, locally advanced stage, and distant metastasis respectively; T<5 cm was found in 29.9% subjects, while 70.1% subjects had T≥5; 67.2% subjects presented with N-, while 32.8% subjects were N+. The most common histological type was infiltrating ductal (82% of subjects). P53 mutant and AR expressions were positive in 44.8% and 15% subjects, respectively. Basal-like subtype presented with younger age at and had higher expression of AR, while non-basal-like subtype is associated with BMI ≥25 (p<0.05). Basal-like subjects had shorter overall survival (23.9 months (95% CI: 21.9-25.9) vs. 26.1 months (95% CI: 23-29.2).CONCLUSION: Basal-like subtype is associated with worse prognosis, younger age at diagnosis and increased expression of AR, while non-basal-like subtype is associated with higher BMI in Indonesian TNBC.KEYWORDS: TNBC, subtype; basal-like, young age, Indonesia
Clinicopathological Characteristic and Prognostic Significance of Indonesian Triple Negative Breast Cancer Irianiwati Widodo; Ery Kus Dwianingsih; Teguh Aryandono; Soeripto Soeripto
The Indonesian Biomedical Journal Vol 11, No 3 (2019)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v11i3.831

Abstract

BACKGROUND: Triple negative breast cancer (TNBC) is a breast cancer subtype with negative expressions of estrogen receptors (ER), progesterone receptors (PR) and Her-2 protein receptors. This subtype exhibits aggressive behavior and poor prognosis since it is unresponsive to hormonal and Her-2 targeted therapy. The identification of clinicopathological characteristics and their prognostic values will provide guidance in developing effective treatment. This study was performed to analyze the clinicopathological characteristics and prognostic significance in Indonesian TNBC.METHODS: Forty paraffin-embedded tissues of TNBC, stage I to IIIA, dating from 2008 to 2010 in Dr. Sardjito Hospital, were enrolled. Survival follow-up was done from January 2008 to June 2013. The samples were immunostained with ER, PR and Her-2 monoclonal antibodies to determine the TNBC subtypes. The clinicopathological characteristics were statistically analyzed. The survival was analyzed using the Kaplan Meier method. The Cox proportional hazards model was used for multivariate analysis.RESULTS: Mean age of TNBC patients was 51.42±11.72 years old, whereas the mean of tumor size was 5.4±2.92 cm. Lymph node metastasis was found in 70% of cases. Number of locally advanced samples (IIIA) was 37.5%, while moderate to high grade samples were 95%. Number of still alive patients at the end of the study was 55%. Number of patients that still alive up to the end of the study was 45.50%. Lymph node was an independent prognostic factor for survival of TNBC patients as positive status of lymph node increases the death risk to 6 times higher (p=0.02, RR=6.6). However, after being adjusted with age and stage, lymph node status was suggested as a modifier effect for the survival of TNBCs patients (RR=0.19).CONCLUSION: Indonesian TNBC patients were mostly found already with large tumor size, lymph node metastasis, high pathological grade and relatively young age. Lymph node status serves as a modifier effect for the survival of Indonesian TNBC.KEYWORDS: NBC, clinicopathological characteristics, prognostic significance