Lung cancer is a leading cause of cancer mortality worldwide and patients occasionally develop local recurrence or distant metastasis soon after curative resection. Reports of new therapeutic strategies for lung squamous cell carcinoma (SqCC) are extremely rare, while selective anticancer therapy has been reported for lung adenocarcinoma. The aim of this study was to identify clinicopathological prognostic factors for SqCC. We analyzed tumor budding and infiltrative patterns (INF) in 103 cases of surgically-resected SqCC. Tumor infiltrative patterns were classified into three groups (INFa, b and c) and INFc was infiltrative growth at the tumor invasive front. The cases with an INFc component [INFc(+)]were significantly associated with venous invasion (P=0.014) and the scirrhous stromal type (P<0.001). The overall survival rate of patients with INFc(+) was significantly lower than that of patients without the INFc component [INFc(−); P=0.003]. Tumor budding was defined as a single cancer cell or a small nest of up to four cancer cells within stromal tissue. The cases with tumor budding [Bud(+)] were significantly associated with lymph node metastasis (P=0.001), lymphatic invasion (P=0.002), INFc(+) (P<0.001) and the scirrhous stromal type (P=0.014). Patients with the Bud(+) type had a lower overall survival rate than patients with the Bud(−) type (P<0.001). Multivariate analysis demonstrated that tumor budding [hazard ratio (HR), 2.766; 95% confidence interval (CI), 1.497–5.109] and lymph node metastasis (HR, 1.937; 95% CI, 1.097–3.419) were independent predictors of mortality. In conclusion, tumor budding is a significant indicator of a high malignant potential and poor prognosis in SqCC of the lung.
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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
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