Genetic and pathologic changes associated with lymphovascular invasion of colorectal adenocarcinoma.

ABSTRACT

Lymphovascular invasion (LVI) is a biological manifestation of aggressive behavior in colorectal cancer. This study sought to identify and examine the association between genetic and pathologic alterations implicated in this invasive tumor progression. We consecutively recruited 81 and 79 colorectal cancer patients with and without LVI, respectively. Biological changes were evaluated by clinicopathological parameters together with CEA and E-cadherin expressions using immune staining. Allelic loss or MSI was examined using 10 microsatellite markers on chromosomes 10, 16, 18, and TGFbetaRII, possibly associated with colorectal cancer. The germline mutation of BMPR1A and SMAD4 was also sought. Tumor stage and lymph node metastasis were significantly greater in patients with LVI tumor than without it (P < 0.001). Decreased CEA expression was closely correlated with allelic loss or MSI at D16S421, D18S46, and D18S474 (P = 0.004-0.047). Allelic loss at D10S14 was specific to LVI tumors (P = 0.007). Using multivariate analysis, allelic loss at D18S46 significantly correlated with histological differentiation (P = 0.02). In addition, allelic loss and MSI at D18S474, histological differentiation, and expression of CEA and E-cadherin were closely associated with the progression of LVI (P = 0.005-0.049). However, no germline mutation in BMPR1A or SMAD4 was detected in all patients regardless of LVI status. In summary, in a subset of colorectal cancers, histological differentiation and expression of CEA or E-cadherin appear to determine aggressive behavior such as LVI. These changes are closely associated with chromosomal alterations at 10q22-23, 16q22 and 18q21, which carry several tumor suppressor genes.