Immunoexpression of Cyclin D1 and PTEN in Various Endometrial Pathologies.

OBJECTIVE: To determine the expression of cyclin D1 and PTEN (phosphatase and tensin homolog) in endometrial hyperplasias and neoplasias. STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: The study was conducted at BMSI, JPMC, Karachi, from January 2008 to December 2012. METHODOLOGY: Analysis of endometrial samples, comprising of hysterectomies and curettage, was carried out. Immunohistochemical staining was done for PTEN and cyclin D1 expression. RESULTS: Fifty-three endometrial samples including 23 endometrial carcinomas, 6 complex hyperplasias with atypia, 14 complex hyperplasias without atypia, 6 simple hyperplasias without atypia and 4 normal proliferative endometrium were analyzed. Fifty-two percent (12 out of 23) and 48% (11 out of 23) cases of endometrial carcinomas showed complete loss of PTEN expression and cyclin D1 over expression, respectively. Five (5 out of 6) cases of complex hyperplasias with atypia and 64.28% (9 out of 14) cases of complex hyperplasia without atypia showed complete loss of or diminished expression of PTEN whereas 66.66% (4 out of 6) cases of endometrial hyperplasia with atypia and 50% (7 out of 14) cases of endometrial hyperplasia without atypia showed cyclin D1 overexpression (p < 0.001). CONCLUSION: Loss of PTEN, expression and cyclin D1 overexpression was seen in a significant number of well differentiated endometrial adenocarcinomas and complex hyperplasias with atypia, suggesting both as an early event in endometrial carcinogenesis.

Correlation of CD24 expression with histological grading and TNM staging of retinoblastoma.

OBJECTIVE: Correlation of CD24 expression with histological grading and TNM staging of retinoblastoma. METHODS: This cross-sectional study was conducted in the Department of Pathology, BMSI, JPMC and NICH from 1(st) January 2009 to 31(st) December 2013. A total 68 diagnosed cases of retinoblastoma were selected for CD24 immuno staining. The data was analyzed by using SPSS version 22. RESULTS: Out of 68 cases 7.35% showed grade 1 followed by 11.76% in G2, 26.47% in G3 and 54.41% in G4. Majority of cases i.e. 60.29% in stage IV followed by 19.11% in stage I, 10.29% each in stage II and stage III. CD24 immuno staining positivity was seen in majority of grade 3 and grade 4. In grade 3, 38.88% showed moderate and 22.22% strong immuno reaction. Amongst grade 4, 40.54% showed moderate and 13.51% strong positive. Variable immuno pattern was observed according to TNM staging. In stage I, 46.15% showed moderate and 7.69% strong positivity, while in stage II, 57.14% were negative for saining. In stage III, 42.85% were negative while 28.57% each showed moderate and strong staining. Majority of cases in stage IV i.e. 48.78% were negative for staining while 34.14%, 17.07% showed moderate and severe CD24 immuno staining. CONCLUSION: Majority of grade I retinoblastoma were in TNM stage I & II and mostly were immuno negative. Lymph node and distant metastatic cases were 75% in G4 and 25% in G3, all of them showed moderate to strong immunoreactivity. These results showed that CD24 expression may be a marker of poor prognosis in retinoblastoma. Whereas TNM staging of retinoblastomas with CD24 expression had varying pattern and showed no significant correlation between them.

Morphological Variants of Renal Carcinoma in Radical Nephrectomy Specimens.

OBJECTIVE: To determine the morphological variants of Renal Cell Carcinoma (RCC) to detect the commonest histopathological type with special focus to the newly introduced entity Clear Cell Papillary Renal Cell Carcinoma (CCPRCC). STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Pathology, Basic Medical Sciences Institute, JPMC, Karachi, from January 2007 to December 2012. METHODOLOGY: Paraffin embedded blocks of 32 cases of radical nephrectomy specimens for renal mass were selected from records of Pathology Department, BMSI. Cases were excluded due to inadequate biopsies. Remaining 30 cases of renal cell carcinoma were included in study. H & E staining was done for all cases and PAS stain was employed for a few cases. All cases were reviewed under light microscope. RESULTS: The 30 cases of renal cell carcinoma included 21 (70%) clear cell renal cell carcinoma, 03 (10%) clear cell papillary renal cell carcinoma, 02 (6.6%) papillary renal cell carcinoma and 04 (13.33%) hybrid tumors. Majority of cases (53.3%) found in age range between 40 - 60 years while 23.33% cases were found in 7th and 6.6% in 8th decade of life. While 16.66% cases were in younger age group that is between 31 - 40 years of age. Sixty percent cases of right radical nephrectomies and 40% cases of left radical nephrectomies. CONCLUSION: CCRCC was most common histopathologic type followed by CCPRCC, hybrid tumors and PRCC.

Differential expression of p63 in hydropic and molar gestations.

OBJECTIVE: To observe the differential expression of p63 in hydropic and molar gestation. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Department of Pathology, Basic Medical Sciences Institute, Jinnah Postgraduate and Medical Centre, Karachi, from January 2006 to June 2013. METHODOLOGY: Ninety placental biopsies including 30 cases each of hydropic abortions, partial hydatidiform mole and complete hydatidiform mole were analyzed for morphological features and results of immunohistochemical staining. Results were described as frequency. Significance was determined using test of proportions with significance at p < 0.05. RESULTS: Out of 30 cases of hydropic abortion, 6 were negative, 15 were weak, 4 were moderate and 5 showed strong degree of intensity for p63. Out of 30 cases of partial hydatidiform mole, 3 were negative, 2 showed weak, 4 showed moderate and 21 cases showed strong degree of intensity for p63. All 30 cases of complete hydatidiform mole strongly stained for p63. CONCLUSION: The intensity of staining of p63 was stronger in cases of molar pregnancy as compared to hydropic abortion. There was loss of p63 expression in cytotrophoblastic cells in all abortions. In limited resources settings, where facilities for PCR/FISH and DNA ploidy analysis is not available, the authors advocate p63 in routine clinical practice to provide the most refined diagnosis of hydatidiform moles.

Review of diagnostic techniques of hepatic fibrosis.

With increasing innovations aimed at the treatment of chronic liver disease (CLD), the precise staging of liver fibrosis is important to help establish efficacious management of disease activity in each patient. The development of biomarkers capable of non-invasive staging of fibrosis in the liver is challenging as fibrogenesis is a part of the normal wound healing response. There is an array of non-invasive methods, including serum biomarker assays, and imaging techniques such as transient elastography. The degree of implementation of non-invasive diagnostic tests for liver fibrosis differs all over the world, and still remains limited. Liver biopsy so far is the mainstay of diagnosing hepatic fibrosis. Precise staging of liver fibrosis is essential in management of patients. This review provides a systematic overview of various techniques, as well as both approaches based on direct and indirect biomarkers to stage fibrosis, and covers recent studies related to hepatic fibrosis.

Glial Fibrillary Acidic Protein (GFAP) as a Mesenchymal marker of Early Hepatic Stellate Cells Activation in Liver Fibrosis in Chronic Hepatitis C Infection.

OBJECTIVE: This study aims to determine expression of Glial Fibrillary Acidic Protein and of Alpha Smooth Muscle Actin (α-SMA) in hepatic stellate cells of CHC cases and their association with stage of fibrosis. METHODS: The study was conducted at Ziauddin University, Clifton Campus during the year 2010-2012. Sixty Chronic Hepatitis C cases were immmunostained using anti α-SMA antibody and anti-GFAP antibody. Semi quantitative scoring in pericentral, periportal and perisinusoidal area of each case was done to assess immunoexpression of each marker. Results : Immunoexpression of GFAP showed significant association with α-SMA. GFAP expression was inversely correlated with progression of fibrosis. Conclusion : GFAP could represent a useful marker for early hepatic stellate cells activation. Follow up biopsies showing decline in GFAP levels may help identify the target group requiring aggressive therapy.

Expression of Von Hippel - Lindau (VHL) gene mutation in diagnosed cases of renal cell carcinoma.

OBJECTIVE: To evaluate the expression of Von Hippel Lindau (VHL) gene in diagnosed cases of renal cell carcinoma. METHODS: This cross sectional study was conducted in department of Pathology, Basic Medical Sciences Institute, JPMC, Karachi, from January 2007 to December 2012. Paraffin embedded blocks of 30 cases of radical nephrectomy specimens diagnosed as renal cell carcinoma including CCRCC 21 (70%) CCPRCC, 3 (10%), PRCC 2 (6.79%), hybrid tumor 4 (13.3%), chromophobe tumor (0%) processed for VHL gene expression on Polymerase Chain Reaction. RESULTS: All the 30 cases previously diagnosed as renal cell carcinoma were processed on PCR, VHL gene mutations were seen in 20 (95.23%) of CCRCC while a single case was negative for VHL mutations. All CCPRCC were negative for VHL mutation. Among the hybrid tumor 03 cases with foci of clear cells show VHL mutation while a single case showing combination of clear cells and chromophobe cells was negative for mutation. Both the cases of PRCC were positive for mutation. Exon 3 mutation at base pair 194 seen in 8 (32%) cases and Exon 2 mutation at base pair 150-159 seen in 17 (68%) cases. None of the cases showed Exon 1 mutation. CONCLUSION: The present study shows that majority of CCRCC showed VHL mutation including the hybrid tumor with clear cell component in our population.

Differential expression of phophatase and tensin homologue in normal, hyperplastic and neoplastic endometrium.

OBJECTIVES: To observe the differential expression of phophatase and tensin homologue in normal proliferative, hyperplastic and malignant endometrial lesions. METHODS: .The retrospective study was based on the analysis of endometrial samples, both hysterectomies and curettage, received at the department of pathology Basic Medical Sciences Institute at the Jinnah Postgraduate Medical Centre, Karachi, from January 1, 2006 to December 31, 2010. A total of 55 endometrial samples were analysed for morphological features and results of immunohistochemical staining. RESULTS: Of the 55 samples, 25 (45.45%) were malignant endometrial lesions, 6 (10.9%) complex hyperplasias with atypia, 14(25.45%) complex hyperplasias without atypia hyperplasia, 6 (10.9%) simple hyperplasias without atypia, and 4 (7.27%) normal proliferative endometrium. Among malignant endometrial lesions, 12 (48%) showed complete loss of phophotase and tensin homologue expression out of which majority were endometroid adenocarcinoma. Five (83.3%) cases of complex hyperplasias with atypia and 9 (64.28%) cases of complex hyperplasia without atypia showed complete loss of or diminished expression of phophotase and tensin homologue. CONCLUSION: Loss of phophotase and tensin homologue expression was seen in a significant number of well differentiated endometrial adenocarcinomas and complex hyperplasias with atypia suggesting loss of PTEN expression as an early event in endometrial carcinogenesis.