Endosialin expression in relation to clinicopathological and biological variables in rectal cancers with a Swedish clinical trial of preoperative radiotherapy

Zhi-Yong Zhang,Hong Zhang,Gunnar Adell,Xiao-Feng Sun

doi:10.1186/1471-2407-11-89

Abstract

BackgroundThe importance of changes in tumour-associated stroma for tumour initiation and progression has been established. Endosialin is expressed in fibroblasts and pericytes of blood vessels in several types of tumours, and is involved in the progression of colorectal cancer. In order to see whether endosialin was related to radiotherapy (RT) response, and clinicopathological and biological variables, we investigated endosialin expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative RT.MethodsEndosialin was immunohistochemically examined in normal mucosa, including distant (n = 72) and adjacent (n = 112) normal mucosa, and primary tumours (n = 135). Seventy-three of 135 patients received surgery alone and 62 received additional preoperative RT.ResultsEndosialin expression in the stroma increased from normal mucosa to tumour (p < 0.0001) both in RT and non-RT group. In the RT group, endosialin expression in the stroma was positively associated with expression of cyclooxygenase-2 (Cox-2) (p = 0.03), p73 (p = 0.01) and phosphates of regenerating liver (PRL) (p = 0.002). Endosialin expression in the tumour cells of both in the RT group (p = 0.01) and the non-RT group (p = 0.06) was observed more often in tumours with an infiltrative growth pattern than in tumours with an expansive growth pattern. In the RT group, endosialin expression in tumour cells was positively related to PRL expression (p = 0.02), whereas in the non-RT group, endosialin expression in tumour cells was positively related to p73 expression (p = 0.01).ConclusionsEndosialin expression may be involved in the progression of rectal cancers, and was related to Cox-2, p73 and PRL expression. However, a direct relationship between endosialin expression and RT responses in patients was not found.

Highlights

The importance of changes in tumour-associated stroma for tumour initiation and progression has been established
We aimed to investigate the relationships of endosialin expression with RT responses, and clinicopathological and biological variables associated with rectal cancers
Endosialin expression in the stroma of distant normal mucosa, adjacent normal mucosa and tumour Endosialin was expressed in fibroblasts and blood vessels in the stroma of normal mucosa, including distant and adjacent normal mucosa, and tumour (Figure 1A-D)

Summary

Introduction

The importance of changes in tumour-associated stroma for tumour initiation and progression has been established. Endosialin is expressed in fibroblasts and pericytes of blood vessels in several types of tumours, and is involved in the progression of colorectal cancer. New surgical techniques [2] and preoperative radiotherapy (RT) [3] have improved the local control and disease-free survival of patients with rectal cancer. The initiation and progression of tumours are influenced by the behaviour of the tumour microenvironment, consisting of the extracellular matrix (ECM), the newly formed vasculature, inflammatory cells and fibroblasts [4,5]. Activated fibroblasts are responsible for the synthesis, deposition and remodelling of the ECM in tumour-associated stroma [4]. Alternative potential targets for inhibiting tumours may be involved in the tumour-associated stroma that contains newly formed blood vessels, active fibroblasts and ECM proteins

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