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

Abstract

AbstractLaminin332 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.