Prevalence of HCV genotypes in patients reporting in tertiary health care hospital of Karachi

The present study was designed to see the variables which may affect the conventional treatment outcome by injection interferon in chronic hepatitis "C" patients. Among these variables hepatitis "C" genotype is most important, as it influences the duration and dosage of anti-viral therapy. To determine the frequency distribution of HCV genotypes, a study was conducted in a tertiary care centre of Karachi, the largest metropolitan city of Pakistan, where people of all ethnic origins are found. All the HCV positive patients, including impatient admitted in hospital and outpatients, more than 18 years of age, reported for genotyping of HCV in the clinical laboratory of Dr. Ziauddin Hospital from May 2009 to April 2010 were studied. HCV genotyping was performed on a total of 457 patients who tested positive for presence of Hepatitis "C" viral RNA. The most prevalent genotype was type 3 with 392 [85.8%] cases, followed by type 1 with 51 [11.2%] cases. There were only two cases with a co-infection of type 1 and 3, while genotype 2,4 and 5 were also seen in a few cases. Among the cases studied, there were higher proportion of females 276 [60.4%], dominating the HCV infected population. The present study revealed that genotype 3 was the most common genotype in patients with HCV infection in Karachi. Other genotypes were also present in the patients infected with HCV, but were of lesser frequency. To prevent the treatment failure it is advisable that before commencement of therapy, the genotype of the patient should be established so that appropriate treatment in correct dosage for optimal duration of time of time could be instituted

Comparative predictive value of three prognostic markers, s-phase fraction, PCNA and mitotic count on axillary lymph node metastasis in carcinoma breast

Axillary lymph node metastasis is the single most important prognostic factor in carcinoma of the breast. Therefore, prognostic markers that may reliably predict probability of lymph node [LN] metastases are of great value. This study was conducted to compare the predictive value of two novel prognostic/ proliferative markers i.e. S-phase fraction [SPF] and proliferating cell nuclear antigen [PCNA] in parallel with mitotic index. Data of consecutive cases of infiltrating ductal carcinoma [IDC] breast diagnosed from July 2003 to July 2004 at the section of the Histopathology, The Aga Khan University Hospital, Karachi, were reviewed. A total of 112 cases of infiltrating ductal carcinoma [IDC] of the breast with axillary LN sampling were selected. SPF was calculated by flow cytometry while PCNA staining was done by immunohistochemistry. Mitotic count was calculated according to modified Bloom and Richardson's grading guidelines. It was observed that the number of axillary LN was found between the results of various categories of PCNA on axillary LN metastases [p value: 0.182] and mitotic count with axillary lymph node metastases [p value: 0.324]. It was concluded that mitotic count and /PCNA alone cannot be used in predicting axillary LN metastases. SPF was found to be a more reliable marker compared to PCNA reactivity and conventional mitotic count in predicting axillary LN metastases

Prognostic value of proliferating cell nuclear antigen [PCNA] in infiltrating ductal carcinoma breast

To assess the independent and interdependent prognostic value of proliferating cell nuclear antigen [PCNA] in carcinoma of breast in our female population and its association with pathologic variables and disease outcome. A descriptive study. Section of Histopathology, Department of Pathology and Microbiology. The Aga Khan University, Karachi from January 1992 to December 1997. All cases diagnosed with invasive ductal carcinomas [IDC] of breast with lymph nodes sampling were included. The expression of PCNA was analyzed on tumor specimens of IDC breast. These patients also had axillary lymph node sampling. The expression of PCNA protein was analyzed immunohistochemically by PAP technique. Patients were followed for a median duration of 48 months. The percentage of PCNA positive tumor cells was estimated semi-quantitatively. Positivity was seen in every case, mean PCNA positivity was 27% [range 10-80] with a median of 28%. The <25% positivity was seen in 149 [47%] cases, and >25% positivity seen in 166 [53%] cases. According to the pathological grading lowest mean PCNA was seen in grade-I i.e., 26% tumor cells showed nuclear reactivity to PCNA followed by grade-II 30% and grade-III 33%. PCNA categorical expression was significantly correlated with histological differentiation, [p<0.05] and tumor size [p<0.01]. Distant metastases were seen in>25% positive cases [p<0.05]. PCNA expression when correlated with overall survival, showed significant correlation between categorical PCNA [p<0.05]. At a median follow-up of 48 months, 66% of <25 PCNA positive patients died with an overall survival of 3.16 years and diseasefree survival of 2.5 years, among >25% PCNA positive patients 77% died with an overall survival of 2.7 years and a disease-free survival of 2.2 years. In this study PCNA proved to be an independent prognostic indicator in predicting disease-free and overall survival in breast carcinoma patients

Characterization of angioimmunoblastic T-cell lymphomas [AILT] and its association with Epstein-Barr Virus [EBV] in Pakistani patients

To characterize angioimmunoblastic T-cell lymphoma [AILT] on morphological, immunohistochemical and molecular grounds and its association with Epstein-Barr virus [EBV] in Pakistani patients. Case series. Histopathology section of the Department of Pathology and Microbiology, The Aga Khan University Hospital, Karachi from January 01, 1992 to December 31, 2002. Over a period of 11 years archival biopsy material of 13 AILT cases [lymph nodes], identified on the basis of histological and immunohistochemical criteria, using REAL and WHO classifications, were retrieved from the files of Department of Pathology. Immunophenotyping was carried out by using CD45 [LCA], two T-cell markers CD45RO [UCHL1; monoclonal] and CD3 [polyclonal]. Polymerase chain reaction [PCR] was used to assess T-cell clonality for T-cell receptor [TCR]-b, g and immunoglobulin heavy chain [IgH] for FR2 and FR3 regions using primers recognizing conserved sequences of the variable [V], diversity [D] and joining [J] region segments. Association of EBV in AILT cases was studied by PCR and in situ hybridization [ISH]. This study showed AILT to constitute 0.71% of all NHLs [non-Hodgkin's lymphoma] [both T and B]. Immunohistochemical study revealed that the tumor cells were positive for CD45 [LCA], CD45RO [UCHL1] and CD3. All the 13 cases were largely negative for CD20 [L26], a B-cell marker, except few large scattered cells labelling. DNA extracted from all 13 lymph nodes was amplified using polymerase chain reaction [PCR]. PCR technique demonstrated clonal gene rearrangement of the TCR-b, g and IgH regions in 3 [23.1%], 7 [53.8%] and 3 [23.1%] AILT cases, respectively out of 13 cases. Association of EBV was seen in 11 out of 13 cases [84.6%] of AILT by PCR. By ISH the prevalence of EBV was detected in 8 [88.8%] out of 9 cases. The prevalence of AILT in the Pakistani population is slightly lower compared to other studies and that EBV is an etiological agent in pathogenesis of this disease