Naila Kayani

Case Control Study of Novel Prognostic Markers and Disease Outcome in Pregnancy/Lactation-associated Breast Carcinoma

A case control study of pregnancy/lactation associated breast carcinoma (PAC) was conducted on 24 test cases with two controls per case, matching age, tumor grade, tumor size and axillary lymph nodes status. During seven years of this study, 6% of all patients with breast cancer had PAC. In this study, 67% of the test cases showed positive axillary lymph nodes compared to 49% in our series of 315 cases of non-pregnancy/non-lactating women with breast carcinoma (p < 0.05). The expression of nine prognostic markers, i.e. ER, PR, p53, C-erbB-2, EGFR, Cathepsin-D, PCNA, DNA ploidy and S-phase fraction, were studied by immunohistochemistry and flow cytometry. Hormone receptor status showed a statistically significant difference between the two groups, i.e. 29% immunoreactivity in test cases compared to 58% in controls with a p value of 0.007. Among p53, C-erbB-2, EGFR and Cathepsin-D in the test group, only EGFR showed a significant correlation, i.e. 33% immunoreactivity in test cases and 19% immunoreactivity in controls (p < 0.05). Higher PCNA positivity was seen in the test group compared to controls, i.e. 35% in test patients and 28% in controls (p < 0.05). Metastasis to bone and liver was a common feature of test patients as compared to controls (p < 0.05). After a median follow-up of 72 months, there was no significant difference in the overall survival (OS) of test cases and controls as 54% deaths were recorded in test patients and 44% in controls at the end of this study (p > 0.05). In summary, in spite of some significant differences in the expression of few prognostic markers, i.e. ER/PR, EGFR, PCNA and metastatic potential, there was no significant difference in the OS of PAC vs. control group if compared stage for stage.

Epidemiology and clinical profile of HIV/AIDS in Pakistan

This study reviews available data on HIV/AIDS in Pakistan and is the first to analyse a clinical series of HIV-infected patients thus giving a wider perspective of the epidemic in Pakistan. A retrospective analysis of all medical records of patients with HIV/AIDS since 1986 was conducted in March 1998 at a Karachi hospital. There were 67 patients. Twenty-two were overseas (Middle East) contract workers. None were sex workers or drug users. Fifty-four had travelled or lived abroad. High risk sexual behaviour was reported in 35 patients of whom 26 men reported contact with commercial sex workers, mostly in the Middle East (21). The most common AIDS indicator condition was chronic diarrhoea. HIV in Pakistan is currently a disease of those Pakistanis (and their sexual partners) who have travelled abroad, overseas contract workers and those who, prior to 1989, were transfused abroad or received imported blood products.

Immunohistochemical cathepsin-D expression in breast cancer: correlation with established pathological parameters and survival.

Breast cancer is an increasingly important cause of illness and death among women. In recent years, several novel prognostic determinants of breast cancer have been identified, including Cathepsin-D (CD) protein. CD protein expression was analyzed immunohistochemically (IHC) in tumor specimens (315 patients) of infiltrating ductal breast carcinoma. These patients also had axillary lymph node sampling. Overexpression of CD was observed in 39% of the tumors. IHC results were compared with the histological grade. Seventy nine percent (n = 95; 79%) tumor positivity was seen in grade II tumors, followed by grade I (n = 13; 11%) and grade III tumors (n = 12; 10%). Axillary lymph node metastasis had no significant correlation with CD positivity (p > 0.05). Bone metastases were significantly correlated with CD positivity (p < 0.05). CD positivity showed no significant correlation with disease-free and overall survival (p > 0.05). At a median follow-up of 48 (4 years) months in CD-positive patients, overall survival was 3.17 years, and disease-free survival 2.67 years. The overall survival of CD-negative tumor patients was 3.50 years, and disease-free survival was 2.93 years. We conclude that in comparison with cytosol-based quantitative studies, CD expression is not a good prognostic marker when, as in all ICH studies, only the expression in the tumor is considered.

Large-Scale pathology-based cancer data - a reflection of population-based cancer data

Pathology-based cancer data is a high quality reflection of the patterns of cancer in the population it represents, provided the demographic details of the patients are carefully recorded. Relative frequency data is neither a replacement for population-based data nor a suggested alternative; it simply enhances the quality of population data and in very large data sets reflects the cancer patterns observed in the representative populations. Aware of the standard shortfalls of pathology-based data, the department of pathology, ‘The Aga Khan University Hospital’ (AKUH) standardized its data, representing 53.4% of the cancer data of Karachi Division (Pakistan) and also reflecting the cancer pattern of other provinces of Pakistan. This data was compared with 4 different population and institutional-based data sets. The findings substantiate the observation that “despite the problems of interpretation of data from pathology laboratories, they are an invaluable source of information on cancer patterns in much of the world where incidence data are unavailable”. If developing countries, unable to organize National Population-Based Registry should as an alternate develop National Pathology-based Registers a well targeted and monitored, a Cancer Control Program would be possible. A good quality, large-scale pathology data with demographic details of the patient recorded can also be extended to give coverage to the population.

Significance of immunohistochemical c-ErbB-2 product localisation pattern for prognosis in human breast cancer

Breast cancer is an increasingly important cause of illness and death among women. In recent years several novel prognostic determinants of breast cancer have been identified, including c-ErbB-2. In this study, expression of c-ErbB-2 in breast carcinoma was correlated with axillary lymph node metastases and disease outcome. The expression of c-ErbB-2 oncoprotein was analysed in 315 tumor specimens of infiltrating ductal carcinoma of breast. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. These patients also had axillary lymph nodes sampling. The expression of c-ErbB-2 oncoprotein was analysed immunohistochemically. Over expression of c-ErbB-2 were observed in 39.36% tumors. Axillary lymph node metastasis had significant correlation with intensified positivity of c-ErbB-2. C-ErbB-2 positive patients did show resistance to chemotherapy when compared for recurrence and distant metastases following surgery (p< 0.05). At a median follow-up of 48 months in c-ErbB-2 positive patients, the overall survival was 3.0 years and disease free survival was 2.5 years. c-ErbB-2 negative tumor patients showed a far better survival. In this group the overall survival was 4.44 years and the disease free survival was 3.78 years. These findings reinforce the view that c-ErbB-2 immunohistochemical detection is of help in detecting a subgroup of breast carcinoma patients who are at high risk. This may also be of particular relevance in decisions regarding adjuvant chemotherapy to these patients.

Anaplastic lymphoma kinase protein positive diffuse large B cell lymphoma; A developing world experience

Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (ALK+DLBCL) is a rare, distinct and aggressive subtype of non-Hodgkins lymphoma (NHL). These tumors are considered to be derived from post-germinal center B cells but peculiarly their distinction is based on the fact that they are ALK-positive neoplastic B cells but lack expression of B cell markers (CD19,CD20, CD79a), T cell markers (CD3, CD5) and CD30. Its broad differential diagnosis and similarities to plasmablastic lymphoma, immunoblastic DLBCL, Anaplastic large-cell lymphoma (ALCL) of T-null cell lineage, and poorly differentiated/anaplastic carcinoma pose a grave challenge to physicians with conventional costly treatment for DLBCL failing to yield any clinical or prognostic significance in ALK+DLBCL. In this article we present 7 cases which were reported at Aga Khan University Hospital, Department of Pathology and Laboratory Medicine from 2009 to 2015 and a review of literature on ALK+ DLBCL, which according to the best of our knowledge is the second largest reported series and the first from South Asian subcontinent.