Tumor Stroma Ratio and Its Significance in Locally Advanced Colorectal Cancer

Abstract

Colorectal cancer is the third leading cause of cancer-related death, and its incidence is rising in the younger patient population. In the past decade, research has unveiled several processes (underlying tumorigenesis, many of which involve interactions between tumor cells and the surrounding tissue or tumor microenvironment (TME). Interactions between components of the TME are mediated at a sub-microscopic level. However, the endpoint of those interactions results in morphologic changes which can be readily assessed at microscopic examination of biopsy and resection specimens. Among these morphologic changes, alteration to the tumor stroma is a new, important determinant of colorectal cancer progression. Different methodologies to estimate the proportion of tumor stroma relative to tumor cells, or tumor stroma ratio (TSR), have been developed. Subsequent validation has supported the prognostic value, reproducibility and feasibility of TSR in various subgroups of colorectal cancer. In this manuscript, we review the literature surrounding TME in colorectal cancer, with a focus on tumor stroma ratio.

Diagnostic yield and repeat biopsies in rectal and nonrectal colorectal adenocarcinoma: Are we hedging on rectal biopsies?

“…With the emerging concept of TNT, tissue diagnosis rendered by pathologists is becoming even more crucial component in rectal cancer management. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 Prospective and multidisciplinary collaborations are warranted to better understand the heterogeneity of CRC management, generate standard-of-care recommendations that are data-driven, and avoid repeat biopsy procedures when unnecessary.…”

“…Also, tumor budding (TB) and tumor stroma ratio (TSR; for treatment-naïve tumors) were assessed. 13 , 14 , 15 …”

Expression Profile of Microenvironmental Factors in the Interface Zone of Colorectal Cancer: Histological-Stromal Biomarkers and Cancer Cell-Cancer-Associated Fibroblast-Related Proteins Combined for the Assessment of Tumor Progression

“…On routine histologic assessment, focusing on the morphologic aspects of the tumor and its composition rather than its anatomical location and behavior, pathologists can recognize prognostically valuable aspects of the TME, such as variations in tumor stroma, the presence of TB, and host inflammatory responses [19]. Furthermore, proteins expressed by microenvironment, derived from cancer cells or stromal cells, can play crucial roles in neoplastic progression [16].…”

“…CRC studies have used these stromal markers to predict tumor characteristics and patient evolution, demonstrating that they somehow play a role in the neoplastic progression of CRC [16]. However, the findings in CRC patients remain unclear, with stromal features and the expression pattern of cancer-CAFrelated proteins, as well as their significance, differing between studies [12,15,[17][18][19]. In this study, we investigated the activity pattern of the elements that collectively make up the TME of CRC and their associations with neoplastic progression features, observing them, in a particular approach, in different interface zones of the tumor mass.…”

Prognostic value and tumour microenvironment characteristics of the Glasgow Microenvironment Score in primary triple-negative breast cancer

“…In addition, the tumour-associated stroma, which mainly consists of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), plays a key role in tumour invasion, metabolic reprogramming and TME remodelling 14 15. A high tumour-stroma percentage (TSP) appears to predict poor prognosis in solid tumours, especially in gastric cancer, colorectal cancer and non-small cell lung cancer 16–18. Higher TSP has also been identified as an independent prognostic marker for reduced survival in patients with primary BC 19 20…”