The tumor-stromal ratio as a strong prognosticator for advanced gastric cancer patients: proposal of a new TSNM staging system

Yan Li,Chunwei Peng,Jiuyang Liu,Guifang Yang

doi:10.1007/s00535-017-1379-1

Abstract

BackgroundInsufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance.MethodsTissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed.ResultsTSR is a new and strong independent prognostic factor for GC patients. The likelihood of tumor invasion is increased significantly for patients in the stromal-high subgroup compared to those in the stromal-low subgroup (P = 0.011). The discrimination ability of TSR was not less than the TNM staging system and was better in patients with stages I and II GC. We integrated the TSR parameter into the TNM staging system and proposed a new TSNM staging system creatively. There were three new subgroups (IC, IIC, IIID). There were four major groups and 10 subgroups in the TSNM system. The difference in overall survival (OS) was statistically significant among all TSNM system (P < 0.005 for all). Deep analyses revealed well predictive performance of the TSNM (P < 0.001).ConclusionsThis study confirms the TSR as a TME prognostic factor for GC. TSR is a candidate TME parameter that could easily be implemented in routine pathology diagnostics, and the TSNM staging system has been established to optimize risk stratification for GC. The value of the TSNM staging system should be validated in further prospective study.

Highlights

Recent figures show that gastric cancer (GC) is the second commonest cause of cancer related mortality in China with over 498,000 deaths in 2015 [1]
Tissue samples consisting of 4 lm hematoxylin and eosin (H&E)-stained sections from the most invasive part of the primary tumor were used for analysis using conventional microscopy
We have shown that TSR is a useful tumor microenvironment (TME) criterion for the prediction of tumor survival in patients with GC

Summary

Introduction

Recent figures show that gastric cancer (GC) is the second commonest cause of cancer related mortality in China with over 498,000 deaths in 2015 [1]. Many new and modified subtypes have been proposed, a tumor-based TNM staging system is still the dominant instrument to guide treatment strategy for GC patients, and insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, which is the underlying cause for tumor heterogeneity, divergent cancer aggressiveness, and clinical outcomes [7, 8]. The TME concept considers the interplay between cancer cells and stromal cells as the primary driving force for cancer progression. Insufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance

Methods

Results

Conclusion