Signet ring cell cancer of stomach and gastro-esophageal junction: molecular alterations, stage-stratified treatment approaches, and future challenges

Abstract

Purpose There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ. Methods A systematic search was carried out in PubMed. Studies available in English related to SRCC of stomach and gastro-esophageal junction were identified and evaluated. Results This study reviewed the current evidence and provided an insight into the molecular alterations, stage-stratified treatment approaches, and future challenges in the management of SRCC of the stomach and GEJ. Specific therapeutic strategies and personalized multimodal treatment have been recommended based on the tumor characteristics of SRCC. Conclusion Multistage carcinogenesis involving genetic and epigenetic aberrations in SRCC is interlinked with stage-dependent prognosis. Specific therapeutic strategy and personalized multimodal treatment should be followed based on the tumor characteristics of SRCC. Endoscopic resection, radical surgery, and perioperative chemotherapy should be offered in carefully selected patients based on stage and prognostic stratification. Future studies in genetic and molecular analysis, histopathological classification, and options of multimodality treatment will improve the prognosis and oncological outcomes in SRCC of gastric and GEJ.

Gastric Signet Ring Cell Carcinoma: An Overview

“…In high-income countries, the incidence of gastro-esophageal junction cancers has increased (2). Recent studies highlight a decreased incidence rate for the intestinal subtype with non-cardial localization; however, there is increased incidence for both intestinal and Lauren diffuse histological subtypes in gastric cardia and gastro-esophageal junction (GEJ) (2)(3)(4).…”

“…For the stomach and GEJ, GSRCC presents at a younger age, at an advanced stage, with lymphatic spread, peritoneal metastasis, rapid progression, and is generally predominant in females (2). There has been much controversy regarding the prognostic value of GSRCC, due to inconsistent results, however, recent research has shown that, for early-stage gastric and GEJ cancer, GSRCC is correlated with better survival in comparison to non-signet cell tumors, whereas the reverse is true for advanced stages (2). For excellent reviews with more coverage of presentation and risk factors, as well as other aspects, see (2,5).…”

“…There has been much controversy regarding the prognostic value of GSRCC, due to inconsistent results, however, recent research has shown that, for early-stage gastric and GEJ cancer, GSRCC is correlated with better survival in comparison to non-signet cell tumors, whereas the reverse is true for advanced stages (2). For excellent reviews with more coverage of presentation and risk factors, as well as other aspects, see (2,5).…”

“…Note that the presented results originate from the Department of Surgery at Taipei Veterans General Hospital, which could explain the overall higher survival values versus other geographic regions ((The Surveillance Epidemiology, End Results (SEER)) database, an authoritative source of cancer statistics in the US, reports a 27.5% 5-year overall survival rate for GSRCC (Tang et al 2020)). For recent reviews that detail clinical management, the reader is referred to (2,12,14).…”

“…An important question is whether the survival rate of early GSRCC is better due to specifics of its tumor biology or other confounding factors. It has been suggested that the better outcomes in early GSRCC with respect to non-signet ring cell gastric cancers could be due to earlier presentation, mucosal restriction of the tumor, and less frequent lymph node invasion (2,5). This suggests that signet ring cell histology is not necessarily an independent predictor for survival.…”