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The study will contribute to the knowledge hiding literature by providing interesting insights in trickledown effect of supervisor knowledge hiding on subordinate knowledge sharing behavior with the co-workers, while; here, LMX as mediator would extend literature of knowledge hiding. Drawing on SET & COR theory by using cross-sectional data collected over structured questionnaire from employees of TEVTA organization, the research will be a considerable addition in both knowledge hiding and knowledge sharing literature. It would also provide the considerable knowledge in OB studies where personality traits i.e., agreeableness as moderator will influence upon relationship of LMX and knowledge sharing by subordinate with coworkers. It argues that, the effects of supervisor knowledge hiding (predictor) not stop at subordinate end while it transmits (trickledown) in coworker and badly affect their social well-being (outcome). More interestingly, agreeableness will moderate relation of LMX & subordinate knowledge sharing behavior with co-workers while the COR will support to author's stance. In addition, theoretical and practical implications of the study are also a key point of the present research. [ABSTRACT FROM AUTHOR]

The leadership, in all respects, is responsible for inspiration of employees toward desired objectives and ultimately the success of organizations. This study aims to analyze effect of transformational leadership on job crafting. This study used structured questionnaire for the data collection purpose. The questionnaire was conducted to personnel from educational sector of in Pakistan. A total of 250 surveys were distributed, with a 97% response rate. SPSS Process Macro was used for the analysis of the data. The findings indicate that psychological ownership improves the association between transformational leadership and job crafting. A healthy work environment minimizes stress and improves performance outcomes. The innovative work behavior is a vital factor that boosts individual towards performance thus leading to organizational success. This study aims to first analyze positive affect the relationship of transformational leadership and job crafting and therefore provides significant contribution to the psychological ownership, and innovative work behavior with mediation and moderation effect and job crafting as dependent variable. This study offered significant outcomes that may help policymakers in revisiting their policies towards the issues under considerations. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the NKX3.1 expression by immunohistochemistry in normal testicular parenchyma and in Sertoli cell tumours and Sertoli Leydig cell tumours of the testes and ovary. Study Design: Retrospective longitudinal study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore Pakistan, from 20102021. Methodology: We used immunohistochemistry to evaluate the positivity and loss of nuclear expression of NKX3.1 in the Sertoli cell tumour (11 cases), Sertoli Leydig cell tumour (31 cases) and in normal testicular parenchyma (7 cases). Results: In our study, there were 49 cases. All the cases of benign testicular parenchyma expressed positivity with nuclear staining of NKX 3.1 in Sertoli cells. Two out of 11 Sertoli cell tumours expressed positivity with nuclear positivity of NKX 3.1 in Sertoli cell component (18.18%) and 9 of the cases showed loss of staining of NKX 3.1 (81.8%). All Sertoli Leydig cell tumours showed loss of staining of NKX 3.1. Conclusion: Nuclear expression of NKX 3.1 is seen in Sertoli cells of normal testicular parenchyma. This staining is lost in Sertoli cell tumours and Sertoli Leydig cell tumours. [ABSTRACT FROM AUTHOR]

Objective: To calculate tumour budding pT2 colorectal carcinomas and study its association with other prognostic indicators. Study Design: Cross-sectional study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research centre, from 2018-2019. Methodology: Hematoxylin and eosin-stained slides of 50 Patients using 4-5 microns' thick sections were prepared using Leica Peloris for processing, Leica ST 5020 for staining and Leica CV 5030 for cover slipping. An Olympus cx31 microscope was used to assess tumour budding. The "Hotspot method" (as proposed by ITBCC) was used. Results: 26 (52%) slides showed low tumour budding (BD1), 8 (16%) showed intermediate tumour budding (BD2), and 16 (32%) showed high tumour budding (BD3). one patient out of 26 had positive nodal status in the low tumour budding category (3.8%). However, at the initial diagnosis, this number was significantly higher in the intermediate (50%) and high tumour budding (37.5%) categories. The mean survival in patients with low tumour budding was 22.615 months, which was significantly higher than 12.250 months and 13.188 months for intermediate and high tumour budding, respectively, with overall mean survival of 17.94 (±5) months. The overall survival rate in our study was 92.30% (24/26 patients), 25% (2/8 patients) and 12.5% (2/16 patients) for BD1, BD2 and BD3 patients, respectively (p=0.001). Conclusion: Our study supports the inclusion of tumour budding in colorectal tumour checklists because of its association with survival and lymph node metastases. [ABSTRACT FROM AUTHOR]

Background: Non-mammary metastasis to the breast poses a diagnostic challenge for the pathologists especially when no prior history of non-mammary malignancy is provided. Since non-mammary metastasis is not a very common occurrence, there is a chance that it can be easily missed especially with overlapping morphology and unknown prior history of any malignancy. Methods: In total, 40 patients matching our inclusion criteria were identified through hospital information system in a 10-year period. Confirmatory stains were used to confirm the diagnosis. Results: The most common primary malignancy site was gastrointestinal tract comprising 35% of the metastasis. This was followed by small cell carcinomas (17.5%). In addition, in 72.5% of the patients, there was a known history of primary malignancy but only in 18 (45%) of the cases, the clinicians mentioned it on the biopsy request form. For the remaining cases (27.5%), the clinician was contacted after the verification of the report and was asked to evaluate the possibility of metastasis from the known primary site. Conclusion: Identifying the non-mammary metastasis is important at the time of initial diagnosis as it can prevent the patient from extensive surgery, which might not be needed, if it is not a primary breast tumor. Provision of prior history and use of immunohistochemical stains can aid in timely and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of chemotherapeutic response on resection specimens and to assess their effect on prognosis. Study Design: Retrospective longitudinal study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Peshawar Pakistan, from Jan 2010 to Mar 2018. Methodology: This study included 42 cases of Ewing sarcoma diagnosed, treated and followed at our institute. Various diagnostic parameters were noted and were assessed for their impact on two-year overall survival, development of distant metastasis, recurrence and cancer-related death. Results: This study included 28 males and 14 females. The majority involved long bones followed by the axial skeleton and soft tissue. Nine cases (9) were confirmed by molecular testing. On the post-neoadjuvant chemotherapy resection specimens, 45% cases had Huvos grade I necrosis, 17% had grade-II, 12% had grade-III and 26% cases had Huvos grade-IV necrosis. Increasing Huvos grade was associated with improved disease-free survival (21%, 43% and 69% for grades-I, II and III/IV respectively). The site and size did not significantly affect the development of recurrence, development of metastasis, or twoyear survival (p>0.05). Conclusion: Meticulous assessment of post neoadjuvant resection specimens for necrosis provides helpful information about the prognostic outcome. Increasing grade of tumour necrosis was associated with increasing disease-free survival. The response to chemotherapy in our study population was worse than Western data, which may be linked to a variety of factors. [ABSTRACT FROM AUTHOR]

Objective: To assess the utility of four immunohistochemical stains in the categorization of hepatoblastoma. Study Design: Retrospective longitudinal study. Place and Duration of Study: Histopathology Department, Shaukat Khanum Memorial Cancer Hospital, Peshawar Pakistan, from 2016 to 2018. Methodology: We retrospectively reviewed 50 cases of hepatoblastoma from 2016-2018, from our hospital database and studied the pattern of four immunohistochemical stains (Beta-catenin, Glutamine synthetase, Heppar 1 and Cyclin D1) in various subtypes. Results: Ten out of fifty cases were mixed epithelial and mesenchymal hepatoblastomas, and forty were pure epithelial. In the pure epithelial category, the fetal subtype showed Heppar 1 and Cyclin D1 positivity in twenty-eight cases, while Glutamine synthetase and Beta-catenin were positive in all the thirty cases. One case of embryonal subtype displayed negativity for Heppar 1; the rest of the immunohistochemical stains were positive. Ten tumours exhibiting mixed epithelial and mesenchymal morphology showed positivity for all the four immunohistochemical stains in the epithelial component. However, Heppar 1 and cyclin D1 were negative in the mesenchymal component in all the ten cases. Five cases (50%) showed Glutamine synthetase and Beta-catenin positivity in the mesenchymal component. Conclusion: All the four immunohistochemical stains, especially Beta-catenin and Glutamine synthetase, were efficient diagnostic tool, especially for tumours with complex or vague morphological features. [ABSTRACT FROM AUTHOR]

BAP1 (BRCA1 associated protein 1 on chromosome 3) is a commonly mutated gene in clear cell renal cell carcinoma. Aim of the study was to evaluate the prognostic significance of BAP1 by immunohistochemistry in clear cell renal cell carcinoma. Methods: It was a descriptive case series in which data was retrospectively collected. Immunohistochemistry was used to evaluate the loss of nuclear expression of BAP1. Results: Loss of BAP1 was observed in 60% of cases of clear cell renal cell carcinoma. 27% of grade 1 tumours, 62% of grade 2 tumours, 65% of grade 3 tumours and 66% of grade 4 tumours showed loss of BAP1. Loss of BAP1 was observed in 54% cases of stage 1 tumours, 72% of stage 2 tumours and 66% of stage 3 tumours. Our study showed loss of BAP1 in 67% of cases with tumour necrosis, in 75% of cases with sarcomatoid features and in 60% of patients with distant metastasis. Conclusions: We conclude that the loss of BAP1 nuclear expression is associated with poor prognostic features. i.e., higher grade, higher stage, tumour necrosis, sarcomatoid features and distant metastasis leading to death of patients. [ABSTRACT FROM AUTHOR]

Objectives: The consensus conference of the International Society of Urological Pathology (ISUP), held in 2012, made recommendations regarding prognostic parameters of renal tumors. There was a strong consensus that tumor morphotype, pathologic tumor stage, and tumor grade are prognostic indicators of poor outcome. It was also agreed upon that prognostic significance of tumor necrosis is in evolution, and both microscopic and macroscopic tumor necrosis should be documented in percentages. The aim of our study was to explore the impact of tumor necrosis on metastasis-free survival in clear cell renal carcinomas (ccRCCs) in Pakistani patients.Methods: We retrieved 318 consecutive in-house cases of ccRCC resections from 2014 to 2020 through hospital archives. Histologic slide review was done for assessment of tumor necrosis, tumor stage, and World Health Organization/ISUP grade. The follow-up data to assess metastasis-free survival were available in hospital archives.Results: In multivariable analysis performed by logistic regression model, tumor necrosis was an independent poor prognostic indicator (P = .0001): group 1 (reference group), 0% necrosis; group 2, 1% to 10% necrosis (adjusted odds ratio [AOR], 8.71; 95% confidence interval [CI], 3.62-20.98); and group 3, more than 10% necrosis (AOR, 9.48; 95% CI, 3.99-22.725).Conclusions: Tumor necrosis is an independent predictor of poor outcome in ccRCCs. [ABSTRACT FROM AUTHOR]

The infiltration of T‐lymphocytes in the stroma and tumour is an indication of an effective immune response against the tumour, resulting in better survival. In this study, our aim was to explore the prognostic significance of tumour‐associated stroma infiltrating lymphocytes (TASILs) in head and neck squamous cell carcinoma (HNSCC) through an AI‐based automated method. A deep learning‐based automated method was employed to segment tumour, tumour‐associated stroma, and lymphocytes in digitally scanned whole slide images of HNSCC tissue slides. The spatial patterns of lymphocytes and tumour‐associated stroma were digitally quantified to compute the tumour‐associated stroma infiltrating lymphocytes score (TASIL‐score). Finally, the prognostic significance of the TASIL‐score for disease‐specific and disease‐free survival was investigated using the Cox proportional hazard analysis. Three different cohorts of haematoxylin and eosin (H&E)‐stained tissue slides of HNSCC cases (n = 537 in total) were studied, including publicly available TCGA head and neck cancer cases. The TASIL‐score carries prognostic significance (p = 0.002) for disease‐specific survival of HNSCC patients. The TASIL‐score also shows a better separation between low‐ and high‐risk patients compared with the manual tumour‐infiltrating lymphocytes (TILs) scoring by pathologists for both disease‐specific and disease‐free survival. A positive correlation of TASIL‐score with molecular estimates of CD8+ T cells was also found, which is in line with existing findings. To the best of our knowledge, this is the first study to automate the quantification of TASILs from routine H&E slides of head and neck cancer. Our TASIL‐score‐based findings are aligned with the clinical knowledge, with the added advantages of objectivity, reproducibility, and strong prognostic value. Although we validated our method on three different cohorts (n = 537 cases in total), a comprehensive evaluation on large multicentric cohorts is required before the proposed digital score can be adopted in clinical practice. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus has become a major emerging health concern. Its burden, estimated to be 451 million in 2017, has been projected to rise to 693 million by 2045. This will bring a rise in the prevalence of its associated complications. There is a wide spectrum of nondiabetic renal disease (NDRD) known to be present in diabetic patients with variable prevalence. However, the majority of diabetes mellitus (DM) patients with renal disease are yet not biopsied and the diagnosis of diabetic nephropathy (DN) is presumed on clinical grounds. Methods: It is a retrospective cross-sectional study. We selected a total of 126 cases of renal biopsies with a history of type 2 diabetes mellitus. Demographic data was collected from the medical records and pathology reports while all cases were evaluated by reviewing the archived slides. Results: Patients were categorized into group 1 with isolated NDRD, group 2 showing NDRD mixed with DN and group 3 with isolated DN. Thirty-four (27%) cases had isolated NDRD (group 1), 14 (11%) had NDRD mixed with DN and 78 (62%) patients had isolated DN. NDRD, either alone or in combination with DN, was found to be present in 48 patients with an overall prevalence of 38%. Conclusion: Our study concludes that NDRD is frequent in type 2 diabetes mellitus patients. Renal biopsy remains the key diagnostic tool in such cases, providing crucial information for proper management of the underlying pathology. [ABSTRACT FROM AUTHOR]

Objective: To assess the patterns of myoinvasion of endometrial endometrioid adenocarcinoma, their frequencies in our hospital and to correlate these patterns with survival. Study Design: Retrospective observational study. Place and Duration of Study: Department of Pathology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, from Aug 2019 to Apr 2020. Methodology: All cases of endometrial endometrioid adenocarcinoma between 2015 and 2017 were retrieved from the archives, independently reviewed by two researchers, all key reporting parameters recorded in addition to the pattern of myoinvasion as per their operational definitions described by Cole and Quick. The follow-up of 3-5 years was obtained from archives and through telephonic contact for outside hospital patients. Disease free survival and relapse-associated mortality were represented through Kaplan-Meier curves. Results: Eighty cases of myoinvasive endometrial endometrioid adenocarcinoma were reviewed. We found that infiltrating irregular gland pattern was the most frequent in all the age groups. Thirty-five (43.75%) cases showed this type of invasion, followed by broad front pattern 23 (28.75%), Microcystic Elongated and Fragmented (MELF) pattern 15 (18.75%) and adenomyotic pattern 6 (7.5%). One case showed a combination of the last two patterns, whereas adenoma malignum pattern was not seen. Follow-up of these patients showed 8 (10%) patients with relapse related mortality including 5 (62.5%) infiltrating irregular glands, 2 (25%) adenomyosis-like and 1 (12.5%) broad front pattern of myoinvasion. Seventy-two (90%) patients had recurrence free survival. Conclusion: Frequency of infiltrating irregular pattern of myoinvasion in endometrial endometrioid adenocarcinoma is high and associated with recurrence related mortality. Recognition of these patterns is important as their impact on overall management and prognosis is, however, unknown, and further studies are required to determine the importance of these patterns. [ABSTRACT FROM AUTHOR]

Background: The 2013 World Health Organization (WHO) classification of soft tissue and bone tumours recognizes benign entities such as lipoma and four major liposarcoma subtypes: atypical lipomatous tumour/well differentiated liposarcomas (ALT/WDL), dedifferentiated liposarcomas (DDL), myxoid liposarcoma and pleomorphic liposarcoma. This classification of atypical and malignant adipocytic tumours has evolved significantly over the past few decades owing to contributions from cytogenetics, molecular genetics and Immunohistochemical correlates. Most ALT/WDLs can be diagnosed on histology; however, some of the biopsies may be underdiagnosed due to focal atypia or limited nature of tissue for the biopsy. Fluorescence in situ hybridization (FISH) for MDM2 (located at 12q14-15) gene amplification has emerged as gold standard for diagnosis in cases with limiting histological factors. Methods: We studied MDM2 amplification by FISH in 55 such problematic adipocytic tumours with overlapping morphological features and a retrospective analysis was made against their corresponding histological features. Results: MDM2 amplification correctly identified 11 of 17 ALT/WDLs (64.71% concordance) and 8 of 10 Lipomas (80% concordance). We were able to differentiate liposarcomas from other high grade sarcomatous lesions and sub-classified these lesions into pleomorphic and dedifferentiated types. Conclusion: FISH for MDM2 amplification should be used as a gold standard in adjunction with morphology and immunohistochemistry for problematic adipocytic neoplasms [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence ERG fusion positive adenocarcinoma and its correlation with gleason grade and gleason group. Study Design: Cross-sectional study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital & Research Centre (SKMCH & RC), Lahore Pakistan, from Jan 2018 to Jan 2019. Methodology: A total of 100 cases of prostatic adenocarcinoma were retrieved and ERG immunohistochemical stain was applied on all these cases. ERG expression, extent of staining, percentage of tumor cells positive for ERG, pattern of staining was recorded. We found out relationship of ERG expression and gleason grade/gleason group. Results: ERG expression was seen in 62/100 (62%) cases. Mean patient age of ERG positive prostatic adenocarcinoma patients was 69.68 years. In GG1 (14.5%) 9 cases exhibited ERG positivity. In GG2-3, 41.93% cases and in GG4-5, 43.54% cases showed ERG expression. Conclusion: To conclude, age of presentation of ERG positive adenocarcinoma was high. ERG expression was seen in 62% of our cases which was much higher than reported in other Asian countries. In our study we found a significant correlation between ERG expression and high gleason grade group. [ABSTRACT FROM AUTHOR]

Background: Post-infectious glomerulonephritis (PIGN) (immune complex-mediated glomerulonephritis) and C3 glomerulopathy are sub-types of glomerulonephritis (GN) with hypercellularity. Both have overlapping clinical and morphologic features on a kidney biopsy, however, the treatment and prognosis of these diseases are quite different making their distinction of utmost importance. Immune complex-mediated glomerulonephritis arises from glomerular deposition of immune-complexes (Igs) and C3 as a result of activation of classical (CP) and lectin pathways (LP). C4d is produced as a result of activation of the CP/LP. On the other hand, C3 glomerulopathy results from activation of alternative pathway of complement. Aim: To distinguish between PIGN and C3 glomerulopathy with the help of C4d IHC stain. Materials and Methods: We studied 28 biopsies reported as GN with hypercellularity from January 2015 to January 2020. Clinical information, histological features and immunofluorescence patterns were analyzed. C4d IHC was performed on all the biopsies. Six known cases of immune complex-mediated GN were selected to act as a positive control for C4d staining. Results: Amongst 28 cases originally reported as GN with hypercellularity, 18 were labeled as post-infectious GN and 10 as C3 glomerulopathy based on clinical information and serological findings. 13 of 18 (72.2%) cases of PIGN had mild to moderate (1– 2+) C4d staining, 2 (11.1%) had strong (3+) staining and 3 (16.7%) cases were negative for C4d staining. In the 10 biopsies of C3 glomerulopathy, mild (1+) C4d staining was noted only in 3 (30%) biopsies. C4d had moderate to strong (2– 3+) staining in the control group. Conclusion: C4d IHC stain can be helpful in distinguishing PIGN from C3 glomerulopathy. [ABSTRACT FROM AUTHOR]

Objective: To assess the sensitivity and specificity of DOG 1 in the diagnosis of chondroblastomas. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from Jun 2015 to Jul 2017. Methodology: Total fifty-two patients were included in this study using simple random sampling technique including 19 chondroblastomas, 21 giant cell tumors and 12 chondromyxoid fibromas. DOG 1 antibody was applied on all the cases. Results: DOG 1 was positive in 100% of cases of chondroblastomas. However, intensity and proportion of staining pattern was variable among them. Fifteen (78%) cases showed diffuse moderate to strong expression while 4 (22%) cases showed focal weak expression. Only 2 (10%) cases of giant cell tumors and 4 (33%) cases of chondromyxoid fibromas expressed focal weak expression for DOG 1. Conclusion: This study confirms 100% expression of DOG 1 in cases of chondroblastomas but intensity and proportion of staining pattern was variable. Therefore DOG 1 may prove to be a useful immunohistochemical marker for diagnosis of chondroblastomas in the future in difficult cases in correlation with histological and radiological features. [ABSTRACT FROM AUTHOR]

Background: Secretory carcinoma of the salivary gland (SC) is a new entity that harbours a specific ETV6 gene rearrangement. The clinical behaviour of this tumour is not well-known as it is a relatively new entity but it is generally considered as a tumour of low malignant potential. The objective of the study was to find out the frequency of ETV6 translocation in cases diagnosed based on histology and immunohistochemistry, to study morphological features and immunohistochemical findings of our cases and to determine the survival and disease-free status of our patients. Methods: Twenty-five diagnosed cases of SC were retrieved from the archives of SKMCH and RC. Diagnosis was made primarily based on morphology and immunohistochemistry. Immunohistochemistry includes S100, p63, mammaglobin, DOG 1, GCDFP-15, TTF-1, GATA3, SMA, AMA, and AR. The diagnosis was further confirmed by molecular testing, i.e., Fluorescence in situ hybridization (FISH) studies to observe specific ETV6 gene break. Follow up of the patients was done by developing a questionnaire. Statistical analysis of the data was done using SPSS-23.0. Results: The mean age of diagnosis was 41±17.4 and the male to female ratio was 1.5:15. The mean size of the tumour was 45.48±27.35. The most common site of the tumour was parotid gland (60%). On morphology, SC showed a wide range of morphological patterns, most common being the tubular, microcystic, intraductal, and papillary. Immunohistochemical stains mammaglobin (22/22), GCDFP-15(15/15) and GATA3 (10/10) showed 100% positive result. However, all cases were negative for p63 (0/18) and DOG 1(0/11). ETV6 break was seen in 17/17 cases (100%). The mean disease-free survival was 75 months and the overall survival was 51.90±2.80 months. Conclusion: This study highlights the presence of specific molecular alteration in all cases, which were diagnosed based on morphology and immunohistochemistry. [ABSTRACT FROM AUTHOR]

Purpose. Clear cell sarcoma of the kidney (CCSK) is an uncommon malignant renal tumor. It is the second most common renal pediatric renal malignancy after Wilms tumor. It exhibits a heterogeneous morphology, with overlapping features with its close differentials, which results in diagnostic challenges. There was no specific immunohistochemical marker in the past, to help in this regard. BCOR antibody has recently been suggested to be helpful in the differential diagnosis. We aim to study the utility of the BCOR antibody in the diagnosis of CCSK. Methods. We selected a total of 27 cases of CCSK (n = 12), Wilms tumor (n = 12), and congenital mesoblastic nephroma (n = 3). All cases were evaluated for the extent and intensity of nuclear labeling for BCOR antibody by immunohistochemistry (IHC). Results. We found that BCOR IHC was positive in 11 out of 12 cases with diffuse and strong staining in 8 of the cases. None of the cases of Wilms tumor and congenital mesoblastic nephroma were positive. Only 2 cases of Wilms tumor showed minimal and weak staining in <5% of cells. Conclusion. Diffuse and strong nuclear staining for the BCOR antibody is highly specific for CCSK among common pediatric renal malignancies. Our study confirms that BCOR IHC is a good IHC marker for the diagnosis of CCSK. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of Ki67 as a surrogate marker for Mitotic Karyorrhectic Index (MKI) in Neuroblastoma. Study Design: Cross-sectional study. Place and Duration of Study: This was a retrospective study conducted at Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. 41 cases of neuroblastoma from 2010 to 2014 were retrieved. Methodology: Forty one cases of neuroblastoma were evaluated. Clinical and morphological features like age, gender and subtype of tumor were quantified. For each case, Mitotic Karyorrhectic Index was calculated and categorized as low, intermediate and high. This was followed by immunostaining for Ki67 on each case. Using linear regression model an equation was derived to calculate ki67 from Mitotic Karyorrhectic Index. The equation was as follows: Mitotic Karyorrhectic Index = (Ki67 x 0.115) ± 1.355. Using this equation, the cut-off values for low, intermediate and high Ki67 were <5.60%, 5.60% - 23.0% and >23.0% respectively. Results: Twenty four cases had low Mitotic Karyorrhectic Index and in 18/24 cases, Ki67 was also low. There were 5 cases with intermediate Mitotic Karyorrhectic Index with two cases showing correspondingly intermediate Ki67 index. There were 12 cases with high Mitotic Karyorrhectic Index and 10/12 cases showed a high Ki67 index as well. Conclusion: Ki67 is a useful technique and may be used as an adjunct to Mitotic Karyorrhectic Index for better evaluation of cases. [ABSTRACT FROM AUTHOR]

Objective: To stratify diffuse gliomas into subtypes including diffuse astrocytomas, oligodendrogliomas and glioblastomas based on recent molecular updates and assess their frequencies in our local subpopulation. Study Design: Cross-sectional study. Place and Duration of Study: Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from Jun 2015 to Jul 2017 Methodology: Two hundred and fourteen (n=214) cases of adult diffuse gliomas were evaluated. Clinical and morphological features like age, gender and type of tumor were quantified. Molecular studies including IDH 1 by antibody and PCR, ATRX by antibody and 1p/19q co-deletion by FISH were tested. Gliomas were subcategorised based on WHO 2016 guidelines. Results: Mean age of presentation was 39 years. Overall n=146/214 (68.2%) of the cases were completely classifiable including Diffuse Astrocytomas, Oligodendrogliomas and Glioblastomas. Out of the glioblastomas (n=81), 67/81(n=82.7%) were IDH Wild type and 14/81 (17.3%) were IDH Mutant. Conclusion: In this study, glioblastomas are the most frequent gliomas as categorized by current WHO molecular guidelines followed by diffuse astrocytomas. Oligodendrogliomas are the least common. [ABSTRACT FROM AUTHOR]

Background: The objective of the study is to analyze the expression of androgen, estrogen and progesterone receptor in different types of endometrial carcinomas and to correlate the androgen receptor expression with estrogen and progesterone receptor and the clinicopathological parameters like lymphovascular invasion, grade of the tumour, size of tumour and extent of myometrial invasion. Methods: It is a cross-sectional analytical study design with a simple random sample of a total of 54 cases of different types of endometrial carcinomas from the year 2017. Immunohistochemical stains androgen receptor, estrogen receptor, and Progesterone receptor were applied in all the cases. The Pearson Chi-square test of independence was applied to measure association and P-value is calculated to check the significance of the results. Results: Androgen receptor expression was observed in 73% of low-grade endometrioid carcinomas, 62.5% of high-grade endometrioid carcinomas, 62% of serous, 20% of clear cell and 18% of carcinosarcomas, respectively. Androgen positive tumours were also positive for estrogen and progesterone in most of the cases, except 3 serous carcinomas and one low-grade endometrioid carcinoma. However, no significant relation was observed between androgen expression and prognostic parameters like the lymphovascular invasion, size of the tumour and myometrial invasion. Conclusion: Maximum expression of androgen receptor was observed in endometrioid and serous carcinomas, while carcinosarcomas and clear cell carcinomas showed minimum expression with no significant correlation between androgen receptor expression and clinicopathological parameters. [ABSTRACT FROM AUTHOR]

We report a novel 1,2-catechol based radioiodinated precursor for radioiodination of bicyclo[6.1.0]nonyne (BCN) installed biologically active molecules using a strain-promoted oxidation-controlled cyclooctyne–1,2-quinone cycloaddition reaction (SPOCQ) under ambient conditions. Compared to the reported methodologies, the new strategy demonstrates some clear advantages, including high in vitro and in vivo stability, high radiochemical yield, and exceptionally fast reaction kinetics at micro-molar concentration. [ABSTRACT FROM AUTHOR]

Objective: To assess the expression of GATA-3 among epithelial tumors of four organs including invasive mammary carcinoma, prostatic adenocarcinoma, colorectal carcinoma and high grade serous carcinoma of ovary. Study Design: Case series study. Place and Duration of Study: The study was performed at Shaukat Khanum Memorial Cancer Hospital and Research Center, from Jul 2017 to Dec 2017. Methodology: Twenty cases of each of these tumors were collected and stained with ready to use GATA-3 immunohistochemical stain (Cell marque (L50-823) mouse monoclonal antibody) using BOND III Leica automated immunostainer. The expression of the antibody was assessed by two histopathologists. Diffuse nuclear staining in more than 30% of tumor cells was considered as positive. Results: All the breast carcinomas showed diffuse strong positivity in tumor cells, while all the cases of prostatic adenocarcinoma showed negative staining. Aberrant and focal staining was observed in a few cases of high grade serous and colorectal carcinomas. Three cases of high grade serous carcinoma showed weak nuclear staining in 10% of cells. Only one case of colorectal carcinoma showed weak nuclear blush in 10 to 20% of tumor cells. Conclusion: GATA-3 was found a sensitive and specific marker for mammary carcinomas. It is a useful diagnostic tool and should be included in a panel of immunohistochemical markers when working on a metastatic tumor of unknown origin. [ABSTRACT FROM AUTHOR]

Background/Aims: New therapeutic strategies and the development of treatments against inflammatory bowel disease (IBD) require the initiation of immune tolerance and inhibition of excessive inflammation. Resveratrol, a polyphenolic compound, is a powerful immunosuppressor, but it can lead to apoptotic death of normal cells at high concentrations. When we induced a structural modification of resveratrol by gamma irradiation, we were able to investigate the potential tolerogenic and anti-inflammatory effect of a new radiolysis product (named γ-Res) during dendritic cell (DC) activation/differentiation. Methods: The potential tolerogenic and anti-inflammatory effect of γ-Res were investigated by cytokine secretion, surface molecule expression, antigen uptake ability, antigen presenting ability, signaling pathway, and mixed lymphocyte reaction (MLR) assay using enzyme-linked immunosorbent assay (ELISA), western blot and flow cytometry. Results: LPS-activated DCs treated with γ-Res exhibited alterations in their mature and functional statuses including a strongly inhibited cytokine production, surface molecule expression, antigen-presenting ability, and activated DC-induced T cell proliferation/activation. In addition, the DCs generated by the γ-Res treatment during DC differentiation induced a decreased surface molecule expression and increased IL-10 production without altering the levels of TNF-α and IL-12p70, thereby promoting the inhibition of T cell proliferation/activation and the induction of regulatory T cells via interaction with DCs in vitro. Furthermore, in the in vivo DSS-induced colitis model, γ-Res treatment conferred protective immunity with a decrease in IFN-γ+CD4+ and IL-17A+CD4+ T cells and imparted protection by reducing the disease activity and histological disease score and increasing the survival rate in dextran sulfate sodium (DSS)-induced colitis in mice. Conclusion: Thus, our results suggest that γ-Res may be an excellent candidate for use in IBD treatment. [ABSTRACT FROM AUTHOR]