Abstract
Expression of the γ2 chain at the invasive front of different tumors has indicated an important role for laminin-5 in cell migration during tumor invasion and tissue remodeling. As there is considerable need for reliable invasion and prognostic markers we evaluated the correlation of laminin-5 γ2 chain expression with clinicopathologic parameters and patient survival in 93 primary colon carcinomas. Epithelial cells of normal mucosa were consistently negative for staining. In contrast, positive cytoplasmic staining was observed in 89 tumors (96%). Twenty-four (26%) cases were scored as sparse, 34 (37%) as moderate, and 31 (33%) as frequent γ2 chain expression. There was a significant association of laminin-5 γ2 chain expression and local invasiveness of colon carcinomas according to Dukes stage (A-C) (p = 0.001) and tumor budding (p < 0.001). A statistical significance could also be noted in decreasing tumor differentiation (p < 0.001) and correlation to tumor size (p = 0.032). No correlation was observed to tumor site. Univariate analysis identified laminin-5 (p = 0.010), tumor differentiation (p = 0.006) and Dukes grade (p < 0.001) as significant variables in predicting prognosis. However, by multivariate analyses, this study could not demonstrate that laminin-5 γ2 chain expression is an independent predictive factor for survival. The results indicate that laminin-5 γ2 chain expression is up-regulated during the progression of human colon cancer and that it plays a role in the aggressiveness of these tumors. Demonstration of laminin-5 γ2 chain positivity also facilitates detection of individual cells or minor cell clusters invading the surrounding stroma.
Highlights
Colon cancer is one of the most common malignant diseases in the western world, ranked as the second leading cause of death from cancer
Laminin-5 γ2 chain expression was examined by immunohistochemistry in a series of 93 primary human colon carcinomas
As previously described for colon carcinoma, positive signals were always cytoplasmic and only detected in cancer cells mainly localized to the invasive front [31,32] (Fig. 1, C and F)
Summary
Colon cancer is one of the most common malignant diseases in the western world, ranked as the second leading cause of death from cancer. The incidence ranges from 25–40 per 100 000 population and the risk of developing colon tumors begins in the fourth decade of life and increases with age. The mean age at presentation is 60–65 years. More than 50% of these patients are expected to die of the disease. This suggests that a significant proportion of micrometasases are present at the time of surgery which can be fatal for the clinical outcome and underline the importance to find reliable prognostic predictors to select patients for adequate additional treatment as a complement to surgery
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