Expression of laminin332 γ2 at the invasive front is associated with tumor budding and poor prognosis in cutaneous squamous cell carcinoma.

Abstract

Laminin332 is a glycoprotein consisting of α3/β3/γ2 chains, of which the γ2 chain (Ln-γ2) is expressed in tumor cells at the invasive front in many types of malignant tumors. We have previously reported that Ln-γ2 is associated with tumor invasion of cutaneous squamous cell carcinoma (cSCC) in vivo and in vitro. Recently, tumor budding (TB; invasion patterns in small clusters of less than five cancer cells in the stroma at the invasive front) has been reported to be a risk factor for lymph node metastasis in cSCC. Based on these findings, we speculated that expression of Ln-γ2 is related to TB in cSCC and would be an invasive factor that causes lymph node metastasis. In this study, we investigated the relationship between Ln-γ2 expression and clinicopathological findings, including TB, in 102 cases of cSCC using immunohistochemistry. The results showed that high expression of Ln-γ2 at the invasive front correlated with a high TB score. In addition, high Ln-γ2 expression at the invasive front was also associated with lymphatic invasion, lymph node metastasis, and poor prognosis (death or recurrence), as in TB. Furthermore, we showed a positive association between Ln-γ2 expression at the invasive front and Yes-associated protein (YAP) expression in the Hippo pathway. Our results suggest that Ln-γ2 expression at the invasive front may have a role in TB formation via YAP and contribute to prognosis by causing lymphatic invasion and lymph node metastasis. The expression of Ln-γ2 would be useful for risk assessment of lymph node metastasis and poor prognosis in routine practice of cSCC.