An Integrative Morphomolecular Classification System of Gastric Carcinoma with Distinct Clinical Outcomes
Journal
American Journal of Surgical Pathology
Journal Volume
44
Journal Issue
8
Pages
1017-1030
Date Issued
2020
Author(s)
Abstract
A robust morphomolecular classification system for gastric carcinoma is required. A 4-tier morphologic classification is proposed, including diffuse, intestinal, tubular, and lymphoid types. A tissue microarray for mismatch repair immunohistochemistry and Epstein-Barr virus (EBV) in situ hybridization were performed in 329 gastric carcinomas. DNA flow cytometry was used to detect aneuploidy in formalin-fixed paraffin-embedded samples. Lymphoid histology was the third most common histologic pattern at our institute and strongly associated with EBV infection and PMS2/MLH1-deficiency (both P#x0003C;0.001). HER2 overexpression and SATB2 expression more frequently occurred in intestinal histology (both P#x0003C;0.001). Loss of ARID1A expression was strikingly associated with lymphoid histology (P#x0003C;0.001) and negative E-cadherin expression was correlated with diffuse histology (P=0.001). Programmed death-ligand 1 expression was most frequently present in lymphoid-type gastric carcinoma than other histologic subtypes and correlated with the molecular features of PMS2/MLH1-deficiency and EBV infection (all P#x0003C;0.001). Aneuploidy was detected in 53#x00025; of gastric carcinomas and was highly correlated with intestinal type and the least with the lymphoid type (P#x0003C;0.001). Notably, lymphoid-type gastric carcinoma showed the best outcome, whereas tubular type showed the worst survival rate (P#x0003C;0.001). We integrated aneuploidy with morphologic patterns to propose a morphomolecular classification scheme, which served as a successful and independent prognostic factor in multivariate 5-year disease-free survival analysis (P#x0003C;0.001). Overall, we describe an integrated morphomolecular classification system for gastric carcinomas to effectively predict patient outcomes. This system is cost-effective and reliable and can help select target therapeutics and facilitate clinical management. Copyright ? 2020 Wolters Kluwer Health, Inc. All rights reserved.
SDGs
Other Subjects
cytoplasm protein; DNA binding protein; epidermal growth factor receptor 2; mismatch repair protein; MutL protein homolog 1; programmed death 1 ligand 1; protein arid1a; protein satb2; unclassified drug; uvomorulin; epidermal growth factor receptor 2; ERBB2 protein, human; matrix attachment region binding protein; mismatch repair protein PMS2; MLH1 protein, human; MutL protein homolog 1; PMS2 protein, human; SATB2 protein, human; transcription factor; tumor marker; adult; aged; aneuploidy; Article; cancer classification; cancer morphology; cancer survival; chromosomal instability; clinical feature; clinical outcome; controlled study; cost effectiveness analysis; demography; disease free survival; DNA content; Epstein Barr virus; Epstein Barr virus infection; female; flow cytometry; fluorescence in situ hybridization; genomic instability; histology; histopathology; human; human cell; human tissue; immunohistochemistry; intestine; lymphoid tissue; major clinical study; male; microsatellite instability; mismatch repair; priority journal; protein expression; stomach carcinoma; tissue microarray; treatment outcome; adenocarcinoma; cancer staging; chemistry; genetics; middle aged; pathology; risk factor; stomach tumor; Taiwan; time factor; very elderly; virology; young adult; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Aneuploidy; Biomarkers, Tumor; Disease-Free Survival; DNA Mismatch Repair; Female; Herpesvirus 4, Human; Humans; Male; Matrix Attachment Region Binding Proteins; Microsatellite Instability; Middle Aged; Mismatch Repair Endonuclease PMS2; MutL Protein Homolog 1; Neoplasm Staging; Receptor, ErbB-2; Risk Factors; Stomach Neoplasms; Taiwan; Time Factors; Transcription Factors; Young Adult
Publisher
Lippincott Williams and Wilkins
Type
journal article