Bronchioloalveolar Carcinoma (Lepidic Growth) Component Is a More Useful Prognostic Factor than Lymph Node Metastasis

Introduction: Although many factors predictive of patient survival have been reported for lung cancer, no comparative studies have attempted to determine those that are most significant for practical medicine. Methods: We conducted a retrospective review of 139 patients who underwent complete resection of adenocarcinomas less than 2 cm in diameter between 1993 and 2000 at the National Cancer Center Hospital (Tokyo, Japan). The MIB-I labeling index (LI), immuno-histochemical staining for carcinoembryonic antigen (CEA), p53, p27, epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), Cox-2, neuronatin, gamma H2AX, and thyroid transcription factor-1 (TTF-1), the prevalence of a micropapillary pattern, and the ratio of the bronchioloalveolar cell carcinoma (BAC) or lepidic growth (LG) component were determined, and their significance as prognostic factors for lung adenocarcinoma was compared. Results: Univariate analysis showed that lymph node metastasis (p-N status), BAC/LG component, vascular invasion (p-V status), MIB-I LI, pEGFR, and CEA were prognostically significant (p-N status:p < 0.0001, BAC/LG:p = 0.0005, p-V status: 0.002, MIB-I LI: p = 0.005, pEGFR: p = 0.024, and CEA: p = 0.049). Multivariate analysis showed that only p-N status (p = 0.013) was of prognostic significance. However, BAC/LG component (p = 0.051) was a more reliable prognostic factor than p-N status in mixed adenocarcinoma with a BAC/LG component. Conclusion: In comparison with other immunohistochemical and histopathologic factors, BAC/LG component is independently and reliably prognostic for small adenocarcinoma of the lung, and, in particular, for the major histologic subtype (adenocarcinoma mixed Subtype with BAC/LG), BAC/LG component is more reliably prognostic than lymph node metastasis.