VEGF Expression in Colorectal Cancer Metastatic Lymph Nodes: Clinicopathological Correlation and Prognostic Significance

Inês Mazeda,Mesquita Rodrigues,Eduardo A. Garcia,Adhemar Longatto,Sandra F. Martins

doi:10.3390/gidisord2030025

Abstract

Background: Angiogenesis plays an important role in colorectal cancer (CRC) tumorigenesis and metastatic progression. Methods: The present series consisted of CRC lymph node metastasis (LNM) tissue samples from 210 patients. Archival paraffin embedded LNM tissue were used to build up tissue microarray blocks and VEGF expression was immunohistochemically assessed. Results: VEGF-A and VEGF-C are overexpressed in LNM. VEGF-A was associated with patient age (p < 0.001), and VEGFR-2 and VEGFR-3 with CRC relapse (p = 0.032; p = 0.030, respectively). VEGF-C positivity was associated with VEGFR-3 positivity (p = 0.031), and VEGF-D with VEGFR-2 and VEGFR-3 (p ≤ 0.001). Matching the expression in LNM with CRC, in CRC VEGF-A positivity associates with VEGF-A, VEGF-C, VEGF-D, VEGF-R2, VEGF-R3 positivity in LNM; CRC VEGF-C with VEGF-D, VEGFR-2, VEGFR-3; CRC VEGFR-2 with VEGF-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3; CRC VEGFR-3 with VEGF-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3 in LNM. Conclusion: This study provides new information, revealing that VEGF family expression is increased in LNM. The association between the expression of VEGFR-2 and VEGFR-3 in LNM with CRC relapse reveals its impact on patient prognosis. Interesting data were found when the relationship between these proteins in primary tumor and their metastasis, were analyzed; VEGFA positivity in primary tumor is positively related to VEGF-A, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in their respective LNM suggesting mutual influence.

Highlights

Colorectal cancer (CRC) is the third most common cancer and the fourth most frequent cause of cancer deaths worldwide [1], being one of the most prevalent diseases of the occidental world [2].There are some well-established prognostic factors in colorectal cancer (CRC)
To literature data, which states that Vascular endothelial growth factor (VEGF)-A is the most abundantly expressed ligand of the VEGF family in primary tumor of CRC [6,8], the pattern of protein staining in lymph nodes showed positive expression of VEGF-A in 60% of CRC metastatic to lymph nodes
We found an interesting association between VEGF-A positivity in CRC samples and the expression of VEGF-C (p = 0.002), VEGF-D (p ≤ 0.001), VEGFR-2 (p = 0.021) and VEGFR-3 (p ≤ 0.001) in their respective lymph node metastasis

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer and the fourth most frequent cause of cancer deaths worldwide [1], being one of the most prevalent diseases of the occidental world [2].There are some well-established prognostic factors in CRC. Pre-operative tumor staging provides essential and relevant prognostic information for choosing adequate therapeutic proceeding, being the factor that best predicts patient survival [3]. Other robust determinants of prognosis include lymphovascular invasion, positive surgical margins, pre-operative increasing of carcinoembryonic antigen (CEA) [4]. These clinicopathological parameters determine the management of patients, they are not reliable predictors of treatment outcome. VEGF-A was associated with patient age (p < 0.001), and VEGFR-2 and VEGFR-3 with CRC relapse (p = 0.032; p = 0.030, respectively). The association between the expression of VEGFR-2 and VEGFR-3 in LNM with CRC relapse reveals its impact on patient prognosis. Interesting data were found when the relationship between these proteins in primary tumor and their metastasis, were analyzed; VEGFA positivity in primary tumor is positively related to VEGF-A, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in their respective LNM suggesting mutual influence

Methods

Discussion

Conclusion