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J Thorac Oncol. 2009 Aug;4(8):951-8. doi: 10.1097/JTO.0b013e3181ad8631.

Bronchioloalveolar carcinoma (lepidic growth) component is a more useful prognostic factor than lymph node metastasis.

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Department of Pathology, Institute of Basic Medical Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.



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.


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-1 labeling index (LI), immunohistochemical staining for carcinoembryonic antigen (CEA), p53, p27, epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), Cox-2, neuronatin, gammaH2AX, 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.


Univariate analysis showed that lymph node metastasis (p-N status), BAC/LG component, vascular invasion (p-V status), MIB-1 LI, pEGFR, and CEA were prognostically significant (p-N status: p < 0.0001, BAC/LG: p = 0.0005, p-V status: 0.002, MIB-1 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.


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.

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