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Elevated Expression of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Promotes Progression of Non-Small Cell Lung Cancer¹

Department of Surgery, Chirurgische Klinik-Innenstadt, University of Munich, 80336 Munich, Germany [W. S., S. D., W. M., B. P.]; Departments of Thoracic Surgery [W. S., B. P.] and Pathology [A. M-H.], Asklepios Fachkliniken München-Gauting, 82131 Gauting, Germany; and Institute of Clinical Chemistry [C. W., J. B.], and Institute for Tumor Biology [U. W., K. P.], University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany

Purpose: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) has recently been implicated in cancer development and progression. This study was performed to assess whether CEACAM-1 expression in primary tumors is correlated to long-term survival in patients with operable non-small cell lung cancer (NSCLC).

Experimental Design: Primary tumors of 145 consecutive patients with completely resected NSCLC (pT_1–4 pN_0–2 M₀ R₀) were stained immunohistochemically using the monoclonal anti-CEACAM-1 antibody 4D1/C2. The prognostic relevance of CEACAM-1 expression was evaluated by univariate Kaplan-Meier and multivariate Cox regression analysis. The median follow-up period was 72 months (range, 10–130 months).

Results: Normal bronchiolar epithelium present in all sections exhibited no immunostaining. In contrast, 73 tumors (50.4%) showed between 1 and 66% CEACAM-1 positive tumor cells, and 72 tumors (49.6%) exhibited even a higher percentage of positive tumor cells. A high CEACAM-1 expression rate (i.e., ≥66% positive tumor cells) was more frequent in adenocarcinomas than in squamous cell carcinomas (61.9 versus 35.7%, respectively). Multivariate Cox regression analysis demonstrated that CEACAM-1 represents an independent prognosticator for cancer-related survival (P = 0.018; relative risk, 1.8; 95% confidence interval, 1.1–2.8). Subgroup analysis revealed that a high CEACAM-1 expression rate was of significant prognostic impact in pN₁-pN₂ patients (n = 60; P = 0.024), pT₃-pT₄ patients (n = 22; P = 0.009), and stage IIa-IIIa patients (n = 69; P = 0.012).

Conclusions: The absence of CEACAM-1 in normal lung tissue and its expression in tumor cells argues against a tumor-suppressive role of CEACAM-1 in NSCLC. The correlation between elevated CEACAM-1 expression and an unfavorable prognosis indicates rather that CEACAM-1 might promote lung cancer progression.

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