Study of HER-2/neu status in adenocarcinoma of stomach and gastroesophageal junction

Background: To study the expression of Human epidermal growth factor receptor 2 (HER-2/neu) in adenocarcinoma of stomach and gastroesophageal junction and to study and describe the association of HER-2/neu expression with various clinicopathological parameters in Indian population.Methods: Immunohistochemical testing was done on 91 cases diagnosed as adenocarcinoma of gastric and gastroesophageal junction by histological examination to determine HER2 status. HER2 amplification was confirmed by fluorescence in situ hybridization (FISH) on cases that had equivocal (immunohistochemistry-IHC score 2+) HER2 expression. The association between HER-2 positivity and clinicopathological parameters was assessed by Chi-square test.Results: The HER-2 IHC results are as follows: score 3+ (positive): 8.79%; score 2+ (equivocal): 10.99%; score 0 and 1+ (negative): 80.22%. Of the 10 cases of equivocal IHC results, 2 cases (20%) showed amplification of HER-2 gene demonstrated by dual probe FISH analysis. The overall prevalence of HER-2 positivity detected using immunohistochemistry and FISH was 10.99% (10/91 cases). HER-2 positivity correlated with the tumor grade (well and moderately differentiated tumor, p=0.013) and intestinal type (p=0.025) but not with age, gender, pathological stage and lymph node metastasis.Conclusions: HER-2 positivity in our study was 10.99%. HER-2 positivity significantly correlated with intestinal type of adenocarcinoma and the grade of the tumor. Two cases with strong HER-2 staining but in less than 10% of the tumor showed gene amplification by FISH

Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer

Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies

A novel glomerular C4d scoring system: A tool to prognosticate proliferative exudative pattern of glomerular injury

Aim: Proliferative exudative pattern of glomerular injury is usually a manifestation of an infection related or a post-infectious glomerulonephritis (PIGN). Rarely, it may represent a C3 glomerulopathy, which is a dysfunction of the alternative pathway of complement activation, and is then termed an atypical PIGN (aPIGN). C4d deposits in the glomerulus are footprints of the classical and/or lectin pathway of complement activation and hence is expected to be positive in immune-mediated glomerulonephritis (GN) like classical infection-related GN, and could be used to differentiate classical PIGN from atypical PIGN. Materials and Methods: We report a novel C4d scoring system based on the intensity and the proportion of glomerular tuft staining, in a series of 104 biopsies with the proliferative exudative pattern of glomerular injury. Using a statistically derived cut-off score of 1.45, the cases were divided into C4d positive and C4d negative groups and compared to IF findings and the follow-up, available in 36 cases. Results: The C4d positive group had a significantly greater proportion of cases with immune complexes compared to the group with C3 deposits alone. In the follow-up, C4d negative group had also a greater number with partial/incomplete response compared to the C4d positive group. Conclusions: We recommend that the C4d stain be done in all cases with a proliferative exudative pattern of glomerular injury to identify patients who would need a close follow up and further assays of complement function

Myoglobinuria-induced acute kidney injury secondary to CovishieldTM vaccination

Vaccination is the best strategy for the development of herd immunity and for the control of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic. As the number of immunizations across the globe reaches a record number, random cases of diverse adverse effects of the vaccines are being documented. We report a case of renal biopsy–proven myoglobin-induced acute tubular injury requiring dialytic support post-CovishieldTM vaccination. Awareness of this rare complication is necessary so that it can be recognized early, and renal injury avoided

Renal transplant biopsies: Recommended guidelines on minimum dataset reporting

Renal allograft biopsies are essential in posttransplant setting to be able to accurately diagnose graft pathologic changes and help in guiding patient management. Banff schema has been long providing guidance to transplant pathologists to accurately diagnose and score the severity of rejections in allograft biopsies. However, there is no standardized minimal data set to report renal transplant biopsies, thereby making it difficult for renal physicians to understand changes in transplant biopsies to adequately manage patients. The present brief review article shall provide guidelines on minimal data set reporting for renal transplant biopsies to bring uniformity in reporting in the whole country

Epidermal growth factor receptor and anaplastic lymphoma kinase mutation in adenocarcinoma lung: Their incidence and correlation with histologic patterns

Introduction: Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational analysis in adenocarcinoma lung are growing in importance as these tests are essential in guiding the use of targeted therapy. However, the prevalence of these mutations in various populations in India has not been studied. Furthermore, the correlation of histologic pattern with the mutation is not clear. Materials and Methods: A total of 64 biopsy-proven lung adenocarcinomas were selected. In 51 of these, EGFR mutational analysis was performed using Qiagen EGFR pyrosequencing kit and in 56 cases of these ALK1 immunohistochemistry (IHC) was done using ALK (D5F3) antibody and the Ventana Benchmark® XT automated IHC slide staining system for the detection of overexpression. The adenocarcinomas were classified into well, moderate, and poorly differentiated, and the histological pattern was recorded according to the WHO 2014 classification. Results: EGFR mutation was positive in 23 cases (45.10%) and positive ALK1 expression by IHC in 12 cases (21.43%). Both mutations were positive in two cases. Both mutations were seen in well-differentiated and moderately differentiated adenocarcinoma, and the expression was highest in tumors with a predominant acinar pattern. Conclusions: The incidence of both EGFR and ALK1 mutations is higher in the population studied and seem to correlate with a well differentiated, acinar pattern on morphology