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

Utility of an Objective Scoring System for Acute Tubular Injury in Renal Allograft Biopsies

Introduction: Banff criteria define various parameters involved in rejection episodes in renal allografts. However, definite objective criteria to diagnose tubular injury are not well addressed. In the present study, we aim to examine a morphological scoring system for diagnosing and grading acute tubular injury in graft biopsies. Furthermore, we assess the correlation of various morphological features of tubular injury with graft dysfunction at the time of biopsy. Materials and Methods: Fifty renal allograft biopsies with a histological diagnosis of acute tubular injury were selected. The inclusion criteria included absence of rejection, significant interstitial inflammation, infection, or interstitial fibrosis/tubular atrophy >10%. The tubular injury was assessed and scored under five parameters: loss of brush border, presence of lucency, flattening of tubular epithelium, loss of nuclei, and presence of cast or debris. All parameters were scored from 0 to 2 based on objective criteria and assessed in five microscopic fields at ×200. A cumulative score was calculated for each biopsy. A correlation with serum creatinine at the time of biopsy with individual scores and cumulative scores was done. Statistical analysis was done and the Pearson correlation coefficient was obtained. Results: All the individual scores of tubular injury showed a positive correlation with serum creatinine at biopsy, with Pearson correlation coefficient varying from 0.670 to 0.490. The cumulative score for tubular injury also showed a strong positive correlation with serum creatinine, with Pearson correlation = 0.761. Conclusion: An objective semi-quantitative morphological scoring system may help in assessing the extent of tubular injury in graft biopsies, as this correlates well with graft dysfunction