Predictive value of WHO classification for PD-L1 and Her2/Neu expression and distinct associations with protein expression based classification in gastric carcinoma.

The Cancer Genome Atlas data on gastric carcinoma has identified four biologic pathways as potential drivers of gastric carcinogenesis and suggested targeted therapies based on the genomic alterations underscoring each subset. The correlation between morphology, biologic groups and their corresponding biomarkers has been eluded in several previous studies; however, a comprehensive analysis in consideration of the recent advancements has not been performed. In this study we explored the predictive value of morphology for biomarker expression and its association with protein expression based classification of gastric carcinoma. Four hundred eighty six gastric carcinomas which had been classified into protein expression-based groups formed the case cohort. Upon analysis, we found a low positive predictive value of an individual morphologic pattern for biomarker-expression, indicating that an individual morphologic pattern alone cannot predict PD-L1, Her2/neu expression and EBV- or MSI-gastric cancer. A combination approach targeting the test in certain WHO patterns can be employed for maximizing the positive predictive values. These include, PD-L1 testing in tubular, carcinoma with lymphoid stroma, undifferentiated and poorly cohesive patterns and Her2/neu testing in tubular, mixed, papillary, mucinous and solid patterns. The predictive values and morphologic associations presented here have the potential to select patients for personalized therapy.

A protein and mRNA expression-based classification of gastric cancer.

The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques.

Endoscopic flushing with pronase improves the quantity and quality of gastric biopsy: a prospective study.

BACKGROUND AND STUDY AIMS: Pronase, a proteolytic enzyme, is known to improve mucosal visibility during esophagogastroduodenoscopy (EGD), but little is known about its effects on gastric biopsy. This study assessed whether endoscopic flushing with pronase improves the quality of gastric biopsy. PATIENTS AND METHODS: Consecutive patients who underwent EGD were randomly assigned to either the control group or the pronase group in a prospective setting. The first biopsy of the identified lesion was performed during endoscopy. Endoscopic flushing with either 50 mL of water and dimethylpolysiloxane (DMPS; control group) or 50 mL of water, pronase, sodium bicarbonate, and DMPS (pronase group) was then applied to the lesion. After 5 minutes, the second biopsy was performed 2 - 3 mm away from the first biopsy site. The thickness of mucus, depth of the specimen, overall diagnostic adequacy, anatomical orientation, and crush artifact were measured to assess the quality of the biopsy. RESULTS: Of the 208 patients, 10 were not analyzed due to the absence of an identifiable lesion. Compared with the control group, the pronase group showed significantly decreased thickness of mucus (P < 0.001), increased depth of biopsy (P < 0.001), improved anatomical orientation (P = 0.010), and improved overall diagnostic assessment (P = 0.011) in the second biopsied specimen following endoscopic flushing. The crush artifact and hemorrhage did not differ between the groups. CONCLUSIONS: Endoscopic flushing with pronase not only improved the depth of biopsy but also the anatomical orientation and overall diagnostic adequacy. Pronase can be recommended for flushing during EGD to improve the quantity and quality of biopsy.

Unclassified mucin phenotype of gastric adenocarcinoma exhibits the highest invasiveness.

BACKGROUND AND AIM: Gastric cancers present with distinctive carcinogenesis pathways that vary with the mucin phenotypes. We attempted to elucidate the relations between the characteristics of the mucin phenotypes of gastric cancer and the tumor invasiveness. METHODS: Gastric adenocarcinomas that were resected surgically between August 2005 and April 2007 were included in the present study. The gastric cancers were subclassified into gastric and intestinal mucin phenotypes if more than 10% of cancer cells exhibited gastric (MUC5AC and/or MUC6) and intestinal (MUC2 or CD10) markers, respectively. RESULTS: The mucin phenotypes of 123 gastric cancers were gastric (n = 31), intestinal (n = 43), mixed (n = 28) and unclassified (n = 21). The mucin phenotype was related to histological type (P < 0.001), Lauren's classification (P = 0.001) and size (P = 0.014) of the gastric adenocarcinoma, but not to its location or to the presence of Helicobacter pylori infection. The unclassified mucin phenotype exhibited the largest number of lymph node metastases (P = 0.007), lymphatic invasions (P < 0.001) and neural invasions (P = 0.026), whereas the intestinal mucin phenotype exhibited the lowest invasiveness. CONCLUSION: The mucin phenotype reflects the biological behavior of gastric cancer, with the intestinal and unclassified mucin phenotypes exhibiting the lowest and highest invasiveness, respectively.