Prognostic value of β1 integrin expression in colorectal liver metastases

Abstract

Integrins are cell surface adhesion molecules (CAM) that regulate via intercellular and cell-matrix signaling various cellular processes including wound healing, cell differentiation, division, growth, migration and metastatic dissemination. Although a correlation between carcinogenesis and changes in integrin expression, especially β1 integrin, has been reported, its role in colorectal liver metastases remains unclear. This study aimed to evaluate the expression of β1 integrin in colorectal liver metastases and to correlate the pattern of expression with clinicopathological features and to investigate the putative role of β1 integrin expression on survival of these patients.

Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples of 81 patients who were operated because of colorectal liver metastases without any neoadjuvant therapy were obtained and stained with hematoxylin and eosin (H & E). An immunohistochemical examination was performed using Dako, Peroxidase/DAB kit and a primary monoclonal β1 integrin (CD29, fibronectin receptor subunit beta; ab3167, Abcam plc). β1 integrin expression was evaluated according to the immunoreactive score of Remmele and Stegner and was related with clinicopathological features of prognostic significance and with disease-free and overall survival as well. Statistical analysis was performed using SPSS version 21.0.

Results: β1 integrin was overexpressed in tumor cells in 37 (48%) patients and in stromal cell in 27 (33%) patients. The β1 expression was not statistically correlated with clinicopathological features of the primary tumors but it was statistically correlated (p=0.03) with the histological grading of liver metastases. Kaplan-Meier survival analysis showed that there is a tendency but no statistically significant correlation in disease-free and overall survival.

Conclusion: Considering that expression of β1 integrin in colorectal liver metastases remains controversial, specially its relation with survival of patients, we showed that the β1 expression represents a reliable prognostic factor regarding the grading of liver metastases of CRC and our findings imply that β1 integrin expression profiles may have further potential in identifying the stage of colorectal liver metastases and being a marker of prognosis in these patients.

Keywords: Colorectal liver metastases; beta1; expression; prognosis; β1 integrin.

Figure 1

Immunohistochemical presentation of the expression of β1 integrin in tumor cells of colorectal liver metastases, poorly differentiated, with positive (A) and negative immunoreactive score (B) and in stromal cells of moderately differentiated metastases with positive (C) and negative (D) immunoreactive score.

Figure 2

A. Kaplan-Meier analysis of overall survival of patients with colorectal liver metastases correlated with immunoreactive score of β1-integrin in tumor cells (positive score: green - negative score: blue, p=0.34); B. Kaplan-Meier analysis of disease free survival of patients with colorectal liver metastases correlated with immunoreactive score of β1-integrin in tumor cells (positive score: green - negative score: blue, p=0.198); C. Kaplan-Meier analysis of overall survival of patients with colorectal liver metastases correlated with immunoreactive score of β1-integrin in stromal cells (positive score: green - negative score: blue, p=0.740); D. Kaplan-Meier analysis of disease free survival of patients with colorectal liver metastases correlated with immunoreactive score of β1-integrin in stromal cells (positive score: green - negative score: blue, p=0.890).