Expression of RCAS1 correlates with urothelial bladder cancer malignancy.

Wojciech Jóźwicki,Anna Brożyna,Andrzej Slominski,Jerzy Siekiera

doi:10.3390/ijms16023783

Abstract

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.

Highlights

A tumor malignancy and its relation to histological structures is a part of histopathological diagnosis
We found that the level of RCAS1 in cancer cells and the number of RCAS1-positive macrophages was higher in the border parts (BPs) of tumors
We found that the histological differentiation of tumor growth dynamics into the central parts (CPs) and BP areas corresponded topographically to the areas of lower and higher RCAS1 expression, respectively, in both tumor cancer cells (Figure 1) and fibroblasts in the tumor microenvironment (Figure 6A)

Summary

Introduction

A tumor malignancy and its relation to histological structures is a part of histopathological diagnosis. The histological maturity of a tumor usually indicates lower potential for malignancy. Histological grading is not a sufficient indicator of the tumor behavior. Among urothelial tumors of the urinary bladder, a group with nonclassic, variant differentiation can be distinguished as tumors in which the malignancy grade correlates with the prominence of a nonclassic structure of the tumor [3,4,5,6,7,8,9,10,11,12]. Urothelial bladder cancers showing divergent differentiation are accompanied by a high grade of malignancy and high stage of advancement of the tumor [12]

Objectives

Discussion

Conclusion