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Background: Quantitative immunohistochemical expression of Androgen receptor (AR) has not been evaluated as a prognostic biomarker of prostate cancer in our population, therefore in the current study we aimed to evaluate the association of AR expression in prostatic acinar adenocarcinoma with various prognostic parameters like tumor quantification, Gleason score, WHO grade group and perineural invasion. Methods: Total 121 cases of biopsy proven prostatic acinar adenocarcinoma were selected from records of pathology department archives from January 2013 till December 2017. Hematoxylin and eosin stained slides and paraffin blocks were retrieved and new sections were cut where necessary. Slides of all cases were reviewed by two senior histopathologists and pathologic characteristics like Gleason score, WHO grade, tumor quantification, perineural and lymphovascular invasion were evaluated. Androgen receptor immunohistochemistry was applied on all cases. Results: Low AR expression was noted in 53 cases (43.8%) while high AR expression was seen in 68 cases (56.2%). Significant association of AR expression was noted with total Gleason score, WHO grade and percentage of tissue involvement (tumor quantification). Univariate binary logistic regression showed patients with low Gleason scores (scores 6,7 or 8) and low WHO grade (grade 1, 2 or 3) were less likely to express high AR expression in comparison to high Gleason score (score 9) and high WHO grade group (grade 5) respectively. Similarly, cases with low tissue involvement by carcinoma (<50%) were less likely to show high AR expression in comparison to cases with >50% tissue involvement by carcinoma. Conclusion: Significant association of AR expression was noted with total Gleason score, WHO grade and percentage of tissue involvement (tumor quantification) which are among the most important markers of tumor progression; therefore we suggest that AR expression should be performed in patients with prostatic adenocarcinoma for prognostic stratification of the patients., (Creative Commons Attribution License)

Background: p16 and p53 genes are frequently mutated in triple negative breast cancer & prognostic value of these mutations have been shown; however, their role as immunohistochemical overexpression has not been fully validated. Therefore we aimed to evaluate the association of p16 and p53 overexpression in triple negative breast cancer with various prognostic parameters., Methods: Total 150 cases of triple negative breast cancers were selected from records of pathology department archives that underwent surgeries at Liaquat National hospital, Karachi from January 2008 till December 2013. ER, PR and Her2neu immunohistochemistry were re-performed to confirm triple negative status. p16 & p53 immunohistochemistry was performed on all cases and association with various clinicopathologic parameters was determined., Results: Mean age of the patients involved in the study was 48.9 years. Most of the patients presented at stage T2 with a high mean ki67 index i.e. 46.9%. 42.7% of cases had nodal metastasis. Although 84% cases were of invasive ductal carcinoma; however a significant proportion of cases were of metaplastic histology (9.3%). Fifty-one percent (76 cases) of cases showed positive p53 expression while 49% (74 cases) were negative. Higher percentage of p53 expression was found to correlate with higher T stage, high ki67 index and higher nodal stage. On the other hand, strong intensity of p53 expression was positively correlated with higher tumor grade and ki67 index. Seventy-one percent (98 cases) of cases showed positive p16 expression, whereas 24.8% (34 cases) were negative and 3.6% (5 cases) showed focal positive p16 expression. However, no significant association was found between p16 expression and various clinical and pathologic parameters. Similarly, no significant association of either p16 or p53 over-expression was noted with recurrence status of patients., Conclusion: On the basis of significant association of p53 over-expression with worse prognostic factors in triple negative breast cancer, therefore we suggest that more large scale studies are needed to validate this finding in loco-regional population. Moreover, high expression of p16 in triple negative breast cancer suggests a potential role of this biomarker in triple negative breast cancer pathogenesis which should be investigated with molecular based research in our population., Competing Interests: Ethics committee of Liaquat National Hospital, Karachi, Pakistan approved the study. Written informed consent was obtained from the patients for the participation.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: Immunohistochemical over expression of p53 is considered as a marker of poor prognosis in many cancers. Therefore, we aimed to evaluate immunohistochemical overexpression of p53 in 121 cases of head and neck Squamous cell carcinoma and its association with various clinicopathologic features and survival., Results: Total 66.1% (80 cases) expressed positive p53 expression, 34% (29 cases) revealed no p53 expression, while focal positive p53 expression was noted in 9.9% (12 Cases). Moreover, high p53 expression (> 70%) was noted in 26.4% (32 cases), while 19% (23 cases) showed 51-70% p53 expression. On the basis of intensity of p53 staining; strong p53 expression was noted in 39.7% (48 cases), while 24.8% (30 cases) and 10.7% (13 cases) revealed intermediate and weak p53 expression respectively. Significant association of p53 intensity of expression with extranodal extension and higher tumor grade (grades II and III) was noted. p53 is useful prognostic biomarker in head and neck Squamous cell carcinoma and therefore we suggest that more large scale studies are needed to evaluate its prognostic significance in our population.

Background: In this study, we intend to determine the immunohistochemical expression of EGFR in cases of head and neck squamous cell carcinoma and its association with prognostic clinico-pathologic features., Methods: A total of 115 cases of head and neck squamous cell carcinoma treated at Liaquat National Hospital, Karachi, Pakistan, were included in the study. Clinico-pathologic features, risk factors, and recurrence status of cases were evaluated, and EGFR immunohistochemistry was performed., Results: In our study, 52 cases (45.2%) of head and neck SCC were positive and 10 cases (8.7%) were focal positive for EGFR expression, while 53 cases (46.1%) were negative for EGFR expression. High EGFR expression (> 70%) was noted in 6.1% (7 cases), while 12.2% (14 cases) and 26.1% (30 cases) revealed 51-70% and 11-50% EGFR expression respectively. On the basis of intensity, strong EGFR expression was noted in 13.9% (16 cases) while 16.5% (19 cases) and 23.5% (27 cases) revealed intermediate and weak EGFR expression respectively. Significant association of EGFR expression was noted with tumor stage and disease-free survival., Conclusion: We found a significant association of EGFR expression with tumor stage and disease-free survivals, which are the most important prognostic factors in head and neck squamous cell carcinoma; therefore, EGFR expression can help as a prognostic biomarker in head and neck squamous cell carcinoma. On the other hand, we suggest that molecular studies should be performed in squamous cell carcinoma of head and neck in our setup to identify patients that can avail response from anti-EGFR therapy.

Objective: Cytokeratin 5/6 and Cytokeratin 8/18 are basal and luminal markers of breast cancer and they have pathological and prognostic significance in breast cancer. We performed Cytokeratin 5/6 and CK8/18 immunohistochemistry on 150 cases of triple negative breast cancers and association with various clinicopathological features was evaluated., Results: Positive CK5/6 expression was noted in 8% (12 cases) of TNBC while 2.4% (4 cases) showed focal positive (< 10%) and 89.3% (134) were negative with CK5/6. Complete loss of CK8/18 expression was seen in 4.7% (7 cases) while 32.7% (49 cases) revealed focal loss of CK8/18 and 62.7% (94 cases) showed intact normal expression of CK8/18. No significant association of CK5/6 and CK8/18 with various clinicopathological parameters was observed. We found a low expression of basal cytokeratin (CK5/6) in TNBC our studied population, while loss/altered expression of CK8/18 in approximately 38% of TNBC. Although no prognostic relevance of these finding was noted in our study, however these findings are different from those reported in literature in other parts of the world. Therefore we suggest a more through immunohistochemical and genomic profiling of TNBC in our population for better understanding of this disease in this part of the world.

Background: Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population., Methods: We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated., Results: High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival., Conclusion: Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

Objectives: Recent evidence suggests a role of androgen receptor expression as a prognostic and therapeutic biomarker in endometrial carcinoma, therefore in the present study we aimed to evaluate the frequency of androgen expression in different subtypes of endometrial carcinoma and its association with clinic-pathologic features., Results: 18/89 (20.2%) cases of endometrial carcinoma showed positive androgen receptor expression. On the other hand, low, moderate and high androgen receptor expression was noted in 7/89 (7.9%), 10/89 (11.2%) and 1/89 (1.1%) cases respectively. 15/77 (19.48%) of endometrioid cancers and 3/7 (42.28%) cases of serous carcinoma showed androgen receptor expression; while none of the cases of clear cell or carcinosarcoma revealed androgen receptor expression. No significant association of androgen receptor expression with various clinicopathologic features of endometrial carcinoma was noted. We found that a significant subset of endometrial cancers express androgen receptor especially a serous cancers; therefore we suggest that androgen receptor expression testing should be done in endometrial carcinoma.

Objectives: Well differentiated keratinized squamous component as a part of urothelial carcinoma can be easily appreciated; however non-keratinizing squamous differentiation closely resembles urothelial differentiation. In addition prognostic significance of CK 5/6 expression in the absence of apparent squamous differentiation is still unclear. Therefore, in the present study we aimed to evaluate the frequency of CK 5/6 expression in 127 cases of urothelial carcinoma and its prognostic significance in loco-regional population., Results: Positive CK5/6 expression was noted in 6.3% (8 cases) and 13.4% (17 cases) revealed focal positive CK 5/6 expression. On the other hand, 80.3% (102 cases) showed negative CK5/6 staining. Significant association of CK5/6 expression was noted with tumor grade and muscularis propria invasion, however no significant association was noted with overall and disease free survival. On the basis of the results of our study we can conclude that CK5/6 is an independent prognostic biomarker in urothelial carcinoma and therefore can be used in the prognostic stratification of the patients with bladder cancer.

Background: Microsatellite instability (MSI) operates as the second major pathway in the colorectal carcinogenesis. Although genetic testing remains the gold standard for the detection of MSI, the College of American Pathologists (CAP) recommends an initial immunohistochemical workup with a four-antibody panel (MLH1, PMS2, MSH2, and MSH6) to screen for a defective mismatch repair system. An increased trend towards young age colorectal carcinoma (CRC) has been noticed in our population over recent years; however, neither screening for MSI by immunohistochemistry (IHC)/genetic testing was done nor were its morphological features studied. We aimed to determine the frequency of mismatch repair deficiency (dMMR) by loss of IHC expression of the aforementioned enzymes in CRC patients and its correlatation with clinicopathologic parameters., Methods: This was a retrospective study conducted at Liaquat National Hospital, Karachi, between 2012 and 2015. A total of 100 cases of CRC were included in the study that underwent surgical resection. IHC stains using antibodies MLH1, PMS2, MSH2, and MSH6 were performed by DAKO EnVision method on representative tissue blocks. The results were interpreted by senior histopathologists and correlated with clinico-pathological parameters., Results: A total of 100 cases of CRC were studied that included 51 males and 49 females. Thirty-four percent (n = 34) of the patients showed loss of IHC staining for MMR markers. Combined loss of expression for MLH1/PMS2 were observed in 16% (n = 16) of the cases. Loss of MSH2/MSH6 were seen in 6% (n = 6) of the cases. Loss of expression for all markers were noted in 7% (n = 7) of the cases. There were 5% (n = 5) of the cases that showed isolated loss of MLH1 only. The tumors with dMMR status were significantly associated with right-sided location (p = 0.013), exhibited intra-tumoral lymphocytosis (p = 0.007), and lymphovascular invasion (p = 0.043). No significant association was seen with gender, age, tumor stage, grade, or other morphological features., Conclusion: The frequency of mismatch repair deficiency in CRC patients was found to be 34% in Pakistani population which warrants further genetic testing to exclude Lynch syndrome. Moreover, right-sided location and intra-tumoral lymphocyte count may be used to identify patients who may need further workup.

Background: Hodgkin lymphoma is one of the most prevalent lymphoproliferative disorders in Pakistan; however, no risk factors for this disease have yet to be established in our population. Epstein-Barr virus (EBV) is a well-known risk factor for Hodgkin lymphoma in endemic regions of the world; however, frequency of its association in our population has not been widely studied. Latent membrane protein 1 (LMP1) expression by immunohistochemistry (IHC) is a surrogate marker of EBV in Hodgkin lymphoma. Therefore, we aimed to evaluate the frequency of expression of LMP1 in cases of Hodgkin lymphoma at our institute and its correlation with other clinical and histologic parameters., Methods: The study included 66 cases of Hodgkin lymphoma diagnosed at Liaquat National Hospital over a duration of 2 years from January 2014 to December 2015. The slides and blocks of all cases were retrieved, and representative blocks were selected for LMP1 by IHC. LMP1 expression of >10% of cells was considered as positive expression and correlated with histologic subtypes and clinical parameters like age, gender, and site of involvement., Results: The mean age of patients was 35.11 (+20.22). LMP1 expression was found in 68.1% (45/66) of cases of Hodgkin lymphoma. Mean age of the patients with LMP1 expression was 32.04 (+21.02). LMP1 expression was found in 40% cases of lymphocyte-rich, 66.7% of lymphocyte-depleted, 73.9% of mixed cellularity, 66.7% of nodular sclerosis, and 73.7% of classic Hodgkin lymphoma, NOS. No significant correlation of LMP1 expression with any clinical or histological parameter could be established in our studied patient population., Conclusions: A high frequency of expression of LMP1 is seen in cases of Hodgkin lymphoma at our setup comparable to endemic regions of the world; therefore, preventive and treatment protocols should be designed accordingly.

Background: Ovarian cancer is the most lethal gynecologic malignancy and it represents third most common malignancy in Karachi (after breast and oral cancer). Due to lack of well established cancer registry in our country, changing trends of ovarian tumors has not been determined. Therefore we aimed to establish the current trends and classification of ovarian tumors in our setup according to latest WHO guidelines., Methods: We retrospectively analyzed 162 cases of ovarian tumors that underwent surgical resection from January 2009 till December 2014. Specimens were received in histopathology department, Liaquat National hospital and cases were examined by senior histopathologists and classified according to latest WHO guidelines. Various histopathologic parameters including capsular invasion, omental and lymph node meatstasis along with uterine and fallopian tube involvement were determined apart from tumor type and grade., Results: Mean age at diagnosis was 35.8 years (± 15.5). surface epithelial tumors were most common, 109 cases (67.2%) followed by germ cell tumors, 44 cases (27.1%) and sex cord stromal tumors, 8 cases (4.9%). Serous tumors were most common surface epithelial tumors with 90% benign morphology. On the other hand, mucinous tumors showed a higher percentage of borderline and malignant features (16.7 and 14.6% respectively). Higher incidence of capsular invasion and omental metastasis was noted in endometroid and serous carcinoma compared to mucinous tumors., Conclusions: We noted a higher frequency of young age ovarian cancers in our set up. Serous and endometroid carcinomas were found to be associated with adverse prognostic factors like capsular invasion and omental metastasis. Moreover a significantly higher proportion of ovarian tumors constitute mucinous histology including borderline tumors. Whether this represents a changing trend towards biology of these tumors in this part of the world needs to be uncovered by further studies.

Background: Renal cancer is a serious public health problem which may be under reported and registered in our setup, since the Karachi cancer registry documented only 43 cases out of 4,268 incident cancer cases over 3 year duration. Therefore we aimed to determine the clinicopathologic characteristics of adult renal tumors in our setup., Materials and Methods: The study was conducted in histopathology department, Liaquat National Hospital and included total of 68 cases of adult renal tumors over 4 years. Detailed histopathologic characteristics of tumors were analyzed., Results: Mean age of patients was 56.4 (18-84) years. Renal cell carcinoma (RCC) was the most common cell type (78%) cases; followed by transitional/urothelial carcinoma (12.5%), leiomyosarcoma (4.7%), oncocytoma (1.6%), squamous cell carcinoma (1.6%) and high grade pleomorphic undifferentiated sarcoma (1.6%). Among 50 RCC cases; 62% were conventional/clear cell RCC (CCRCC) type followed by papillary RCC(PRCC), 24%; chromophobe RCC(CRCC), 6% and sarcomatoid RCC(SRCC), 8%. Mean tumor size for RCC was 7.2 cm. Most RCCs were intermediate to high grade (60% and 40% respectively). Capsular invasion, renal sinus invasion, adrenal gland involvement and renal vein invasion was seen in 40%, 18%, 2% and 10% of cases respectively., Conclusions: We found that RCC presents at an earlier age in our setup compared to Western populations. Tumor size was significantly larger and most of the tumors were of intermediate to high grade. This reflects late presentation of patients after disease progression which necessitates effective measures to be taken in primary care setup to diagnose this disease at an early stage.

Background: Non-hodgkin lymphoma (NHL) is a diverse group of disease encompassing divergent tumor types with contrasting clinical behaviors. We aimed to evaluate the usefulness of Ki67 index in segregating indolent from aggressive NHL and its association with clinical parameters., Materials and Methods: During a study period of 4.5 years, a total of 215 cases of lymphomas were diagnosed among of which 172 cases were NHL. Ki67 immunohistochemical staining was performed by the DAKO envision method. Average proportion of tumor cells stained was calculated to determine the proliferative index., Results: The mean age at diagnosis was 46.2 years +19.8 (3-81) with a male to female ratio of 1.5:1. Mean Ki67 index for indolent NHL included 23% for small cell, 25% for mantle cell, 28.5% for marginal zone and 34.6% for follicular lymphoma. On the other hand, mean Ki67 index for aggressive lymphomas were 66.4%, 66.9%, 80.3%, 83.3% and 94.4% for diffuse large B cell, T cell (NOS), anaplastic large cell, lymphoblastic and burkitts lymphoma respectively. No significant correlation was found between Ki67 index and other clinical parameters like age and extra nodal involvement., Conclusions: Ki67 index is a valuable IHC marker to distinguish indolent from aggressive lymphomas especially in small needle biopsies where exact typing may not be possible.

Objective: A cross-sectional hospital based study was carried out to investigate clinical features and outcome of cerebral malaria in a rural area., Methods: All children fulfilling inclusion criteria, were enrolled and were entered on specially designed proforma. Their peripheral smear (PS) were studied based on which the diagnosis was classified as definite cerebral malaria (DCM) and probable cerebral malaria (PCM)., Result: There were 2991 admissions in pediatric ward, of which 1394 (46.6%) were for fever. Of 781 (56.6%) cases with fever no cause was identified. Of the 56 cases positive for malarial parasite on PS 4.3% were Plasmodium vivax (PV) and 2.8% Plasmodium falciparum (PF). Fifteen patients fulfilled the criteria for study of which 7 were DCM and 8 belonged to PCM group. Twelve (80%) were in school-going age group and M : F ratio was 2 : 1. All patients presented with fever, and CNS involvement, 66.6% had convulsion, 7 developed coma, anaemia was seen in 60%, but only 20% required blood transfusion. Splenomegaly and hepatomegaly was seen in 53.3% and 47% cases respectively. Two patients died, one each in DCM and PCM. Cerebral malaria is a serious complication of severe falciparum malaria and is seen in approximately 32% of PF positive cases., Conclusion: PCM is an entity which should be kept in mind when treating fever without definite focus in rural areas, because timely and specific therapy is lifesaving.