Objective: Recent technologic developments in computed tomography have increased the incidence of surgical intervention for small-sized lung cancer. Although indications of a sublobar resection for early disease have been discussed, we occasionally encounter locally advanced small-sized lung cancer with node metastasis. The present study aimed to clarify the histopathologic factors influencing nodal involvement and prognosis of such patients.
Methods: We studied 97 patients who underwent complete resection for an adenocarcinoma of 2 cm or less in diameter. Lymph node metastasis and necrosis were microscopically evaluated, whereas immunohistochemical studies were also performed with Ki-67 and D2-40 for proliferation activity and lymphatic invasion, respectively. In addition, carcinoembryonic antigen expression in the tumor and its level in serum were investigated. Survival analysis was then conducted by using these clinicopathologic factors.
Results: The 5-year disease-free survival rate was 90%. Nodal involvement was significantly frequent in patients with tumors showing microscopic necrosis, a Ki-67 labeling index of greater than 5%, and an increased serum carcinoembryonic antigen level. Furthermore, 5-year disease-free survival was worse in patients with lesions showing microscopic necrosis (68%), a Ki-67 labeling index of greater than 5% (76%), and lymphatic invasion detected with D2-40 staining (77%). Multivariate analysis identified lymphatic invasion detected with D2-40 to be an independent predictor for postoperative recurrence.
Conclusions: These results indicate that microscopic necrosis, Ki-67 labeling index, and serum carcinoembryonic antigen level are predictors of nodal involvement. Careful postoperative follow-up examinations for recurrence are required for patients with tumors that show microscopic necrosis, high Ki-67 labeling index, and lymphatic invasion, even in those with stage IA disease.