Laminin-5^|^gamma;2 chain expression is associated with tumor cell invasiveness and prognosis of lung squamous cell carcinoma

Abstract

Our previous study showed that tumor budding is a significant indicator of a poor prognosis in lung squamous cell carcinoma patients. Tumor budding-positive (Bud(+)) cases of lung squamous cell carcinoma (SqCC) showed locally aggressive growth, and the positivity was a useful indicator of the lymph node status and prognosis. The present study focused on the clinicopathologic significance of laminin-5γ2 chain expression for local aggressiveness in lung SqCC. Laminin-5γ2 chain immunohistochemical stains in tissue samples were divided into three distinct types: basement membrane (B type; laminin-5γ2 present in basement membrane), cytoplasmic (C type; laminin- 5γ2 present in intracellular matrix), and invasive front (F type; laminin-5γ2 present in cytoplasm, and strongly in part of peripheral nest). The F type was more common in Bud(+) cases than tumor budding-negative (Bud(-)) cases; B and C types were less common in Bud(+) cases (P 〈 0.001). The F type was more closely associated with decreased overall survival than the B and C types (P 〈 0.001 for both). Univariate analysis showed that the F type could be used to predict tumor size, lymph node metastasis, lymphatic invasion, tumor infiltrative patterns, tumor budding, and laminin-5γ2 chain staining. Multivariate analysis showed that laminin-5γ2 chain staining and tumor budding could be used to predict patient mortality (P 〈 0.001 and P = 0.005, respectively). The overall survival rate after curative resection was lower in patients with the F/Bud(+) type than in those with B+C/Bud(-) and B+C/Bud(+) types (P < 0.001 for both, log-rank test), and also lower with the F/Bud(-) type than the B+C/Bud(-) type. On the other hand, there was no significant difference between the F/Bud(+) and F/Bud(-) types. In conclusion, both laminin- 5γ2 chain staining and tumor budding are associated with tumor cell invasiveness and are independent predictors of mortality in lung SqCC patients.