Solid-type poorly differentiated adenocarcinoma of the stomach: clinicopathological and molecular characteristics and histogenesis

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 22; no. 2; pp. 314 - 322
• Main Authors: Arai, Tomio, Matsuda, Yoko, Aida, Junko, Takubo, Kaiyo, Ishiwata, Toshiyuki
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.03.2019; Springer Nature B.V
• Subjects: Abdominal Surgery; Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Cancer Research; Carcinoma; Female; Gastric cancer; Gastroenterology; Glycoproteins; Histogenesis; Humans; Intestine; K-Ras protein; Male; Medicine; Medicine & Public Health; Microsatellite Instability; Middle Aged; MLH1 protein; Mucin; Mutation; Oncology; Original Article; p53 Protein; Stomach; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Surgical Oncology; Stomach; Poorly differentiated adenocarcinoma; Microsatellite instability; Solid carcinoma; Elderly
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-018-0862-6

Background Despite predominant microsatellite instability (MSI) in intestinal-type gastric carcinomas, we found the most frequent MSI in solid-type poorly differentiated adenocarcinoma (PDA). Although this tumor is classified as PDA, it is hypothesized to possess peculiar features among PDAs. The present study aimed to clarify the clinicopathological and molecular characteristics of this tumor. Methods We examined the expression of p53, mismatch-repair proteins, and mucin core glycoproteins; microsatellite status; and mutations in KRAS and BRAF , as well as clinicopathological features, in 54 cases of PDA of the stomach (31 solid-type PDAs and 23 non-solid-type PDAs). Results The proportion (51.6%) of MSI in solid-type PDA was significantly higher than that in non-solid-type PDA (4.5%) ( p  = 0.00022). The proportion of absent expression of MLH1 (58.1%) and PMS2 (51.6%) in solid-type PDA was significantly higher than that in non-solid-type PDA (4.5 and 8%) ( p  < 0.0001). No differences were found in the mutations of KRAS and BRAF among PDAs. MSI-positive solid-type PDA was significantly associated with older age, female predominance, lower third location, concordant glandular component, and absent MLH1 and PMS2 expression. Conclusions These results suggest that MSI-positive solid-type PDA has peculiar clinicopathological features and that MSI with absent MLH1 and PMS2 expression may play an important role in tumor development. In addition, from the viewpoint of histogenesis, MSI-positive solid-type PDA may originate from differentiated-type adenocarcinoma.