Linda W Martin1, Jonathan D'Cunha2, Xiaofei Wang2, Debra Herzan2, Lin Gu2, Naif Abraham2, Todd L Demmy2, Frank C Detterbeck2, Shawn S Groth2, David H Harpole2, Mark J Krasna2, Kemp Kernstine2, Leslie J Kohman2, G Alexander Patterson2, David J Sugarbaker2, Robin T Vollmer2, Michael A Maddaus2, Robert A Kratzke2. 1. Linda W. Martin, University of Maryland Medical School, Baltimore, MD; Jonathan D'Cunha, University of Pittsburgh Medical Center, Pittsburgh, PA; Xiaofei Wang, Lin Gu, and David H. Harpole, Duke University; Robin T. Vollmer, Durham VA Medical Center, Durham, NC; Debra Herzan, Michael A. Maddaus, and Robert A. Kratzke, University of Minnesota, Minneapolis, MN; Naif Abraham and Leslie J. Kohman, State University of New York Upstate Medical University, Syracuse; Todd L. Demmy, Roswell Park Cancer Institute, Buffalo, NY; Frank C. Detterbeck, Yale University, New Haven, CT; Shawn S. Groth and David J. Sugarbaker, Baylor College of Medicine, Houston; Kemp Kernstine, University of Texas Southwestern Medical Center, Dallas, TX; Mark J. Krasna, Jersey Shore University Medical Center, Neptune, NJ; and G. Alexander Patterson, Washington University School of Medicine, St Louis, MO. LM6YB@virginia.edu. 2. Linda W. Martin, University of Maryland Medical School, Baltimore, MD; Jonathan D'Cunha, University of Pittsburgh Medical Center, Pittsburgh, PA; Xiaofei Wang, Lin Gu, and David H. Harpole, Duke University; Robin T. Vollmer, Durham VA Medical Center, Durham, NC; Debra Herzan, Michael A. Maddaus, and Robert A. Kratzke, University of Minnesota, Minneapolis, MN; Naif Abraham and Leslie J. Kohman, State University of New York Upstate Medical University, Syracuse; Todd L. Demmy, Roswell Park Cancer Institute, Buffalo, NY; Frank C. Detterbeck, Yale University, New Haven, CT; Shawn S. Groth and David J. Sugarbaker, Baylor College of Medicine, Houston; Kemp Kernstine, University of Texas Southwestern Medical Center, Dallas, TX; Mark J. Krasna, Jersey Shore University Medical Center, Neptune, NJ; and G. Alexander Patterson, Washington University School of Medicine, St Louis, MO.
Abstract
PURPOSE: Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. MATERIALS AND METHODS: Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. RESULTS: Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. CONCLUSION: NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.
PURPOSE: Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. MATERIALS AND METHODS: Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. RESULTS: Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P = .017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. CONCLUSION:NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.
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