Immunohistochemically Detected Micrometastases in Peribronchial and Mediastinal Lymph Nodes From Patients With T1, N0, M0 Pulmonary Adenocarcinomas

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Abstract
The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.