An Integrative Morphomolecular Classification System of Gastric Carcinoma With Distinct Clinical Outcomes. (August 2020)

• Record Type: Journal Article
• Authors: Tsai, Jia-Huei; Jeng, Yung-Ming; Chen, Kuo-Hsing; Lee, Chia-Hsiang; Yuan, Chang-Tsu; Liau, Jau-Yu
• Is Part Of: American journal of surgical pathology. Volume 44:Number 8(2020)
• Publication Date: 2020-08
• Subjects: classification -- aneuploidy -- lymphoid stroma -- survival; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001521
• Languages: English
• ISSNs: 0147-5185

Abstract

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 <0.001). HER2 overexpression and SATB2 expression more frequently occurred in intestinal histology (both P <0.001). Loss of ARID1A expression was strikingly associated with lymphoid histology ( P <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 <0.001). Aneuploidy was detected in 53% of gastric carcinomas and was highly correlated with intestinal type and the least with the lymphoid type ( P <0.001). Notably, lymphoid-type gastric carcinoma showed the best outcome, whereas tubular type showed the worst survival rate ( P <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 <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. Abstract : Supplemental Digital Content is available in the text.