The Clinicopathological Characteristics And Genetic Alterations of Signet-ring Cell Carcinoma in Gastric Cancer.

Kuo-Hung Huang,Chien-Hsing Lin,Anna Fen-Yau Li,Yi-Ming Shyr,Yee Chao,Ming-Huang Chen,Chew-Wun Wu,Su-Shun Lo,Wen-Liang Fang

doi:10.3390/cancers12082318

Abstract

Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression; immunotherapy and targeted therapy may be beneficial for these patients.

Highlights

Gastric cancer (GC) is the sixth most common cancer and the second most common cause of cancer death worldwide [1]
A meta-analysis study [4] demonstrated that for early GC (T1), signet-ring cell carcinoma (SRC) was associated with a better prognosis than non-SRC, while for advanced GC (T2-T4), SRC had a worse prognosis than non-SRC, which was similar to the findings of our previous report [5]
Univariate analysis showed that patients with SRC were younger and more likely to be female and had more tumors located in the middle stomach, more scirrhous stromal reaction, a more infiltrating type, fewer microsatellite instability-high (MSI-H) tumors, more PIK3CA amplifications, less PD-L1 expression, fewer PI3K/AKT pathway mutations and more advanced Tumor, Node, Metastasis (TNM)

Summary

Introduction

Gastric cancer (GC) is the sixth most common cancer and the second most common cause of cancer death worldwide [1]. Signet-ring cell carcinoma (SRC) is characterized by malignant tumor cells with prominent mucin in the cytoplasm and eccentric crescent-shaped nuclei. According to the classification of the World Health Organization (WHO) [2], SRC is defined as being present in more than 50% of GC tumors. We hypothesize that the genetic alterations between SRC and non-SRC in early and advanced GC may be different, and it deserves investigating whether these genetic alterations are associated with patient survival. The molecular difference between SRC and non-SRC in GC is still unclear; further investigation of the genetic alterations may provide useful information to explain the phenomenon

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