Stromal scoring in advanced colon and rectal cancer: Stroma-rich tumors and their association with aggressive phenotypes

Abstract

Received 2021-04-03 Received in revised form 2021-06-14 Accepted 2021-06-14 INTRODUCTION Cancer is currently recognized as a complex disease composed of several cell types, especially those derived from the surrounding mesenchymal stroma, with which neoplastic cells establish the tumor microenvironment (TME). In this environment, the tumor stroma represents one of the TME components (1–4). Tumor cells explore their stroma, changing its composition in a bi-directional communication, leading to the stromatogenesis. The interaction pathways are varied and complex. Therefore, the stromal tissue is not a passive component that involves the tumor (5). Studies have shown that tumor stroma plays a relevant and diverse role in tumorigenesis, acting in different stages: it facilitates the survival and proliferation of neoplastic cells; promotes epithelial-mesenchymal transition, and local and metastatic spread (6–12). Even in distant and lymph node metastatic sites, stromal components accompany cancer cells (13, 14). In malignant epithelial tumors, the scoring system based on the evaluation of the tumor-stroma proportion (TSP) in sections stained with hematoxylin and eosin (H&E) has been shown to be a good prognostic tool (9,10,15–18). Several international research groups have demonstrated that high amount of stroma contributes to a more aggressive tumor phenotypes (8, 9, 15–17, 19–21). Their goal was to fill the need for and identify new prognostic characteristics that could be used along with the current pathological staging (8, 20). The traditional tumor, lymph node and metastasis (TNM) system that has been used routinely for prognosis estimate and guidance of treatment for certain types of tumors (22, 23), lacks accuracy (21, 24, 25). In colorectal cancer (CRC), new reliable biomarkers are needed to guide personalized treatment (21) since current pathological variables only moderately indicate possible outcome and response to therapy (6, 19, 21). Currently, CRC represents a serious public health problem worldwide, occupying the third place in terms of incidence and the second place in mortality numbers (22), while being little attended by public policies in underdeveloped or developing countries (26). Although the complete biological role of stroma is not yet fully understood (20), in the last 10 years the evaluation of tumor stroma has gained interest due to its simplicity and, above all, to its clinical value as a potential prognostic factor. Furthermore, cancer cells and stroma are being considered as therapeutic targets in treatment strategies for solid tumors (14), in which the quantification of the stromal component may provide additional risk stratification for adaptation to neoadjuvant and adjuvant treatments (8, 15, 20, 27). The aim of this study was to evaluate the relevance of the tumor-stroma proportion and its association with confirmed aggressive phenotypes in a large series of patients diagnosed with cancer of the right/left colon and rectum in Brazil.