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Annals of Oncology Advance Access published online on July 29, 2008
Annals of Oncology, doi:10.1093/annonc/mdn538
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Expression of molecular markers in mediastinal nodes from resected stage I non-small-cell lung cancer (NSCLC): prognostic impact and potential role as markers of occult micrometastases

S. Benlloch1,*,{dagger}, J. M. Galbis-Caravajal5, C. Alenda2, F. M. Peiró2, M. Sanchez-Ronco6, J. M. Rodríguez-Paniagua3, B. Baschwitz3, E. Rojas1 and B. Massutí4

1 Research Unit, Hospital General Universitario de Alicante, Alicante
2 Pathology, Hospital General Universitario de Alicante, Alicante
3 Thoracic Surgery, Hospital General Universitario de Alicante, Alicante
4 Medical Oncology, Hospital General Universitario de Alicante, Alicante
5 Thoracic Surgery, Hospital de La Ribera, Alzira
6 Preventive Medicine and Public Health,Universidad Alcalá de Henares, Madrid, Spain

* Correspondence to: Dr S. Benlloch, Hospital General Universitario de Alicante, Unidad de Investigación, Avda Pintor Baeza 12, Alicante 03010, Spain. Tel: +34935460122; Fax: +34935460172; E-mail: sbenlloch{at}pangaeabiotech.com

Background: Occult lymph node (LN) metastases are clinically relevant and confer a worse prognosis in non-small-cell lung cancer (NSCLC) patients. Current staging methods are unable to identify patients with poor outcome. Their detection requires both a more sensitive and specific technique. We aimed to assess the role of messenger RNA expression in pathologically negative LNs (pN0) of stage I NSCLC patients as markers of occult micrometastases and to correlate the results with local or distant tumor recurrence and survival.

Patients and methods: Potential molecular markers were evaluated in 344 LNs and 38 tumors by quantitative real-time RT-PCR. Only CEACAM5 and PLUNC showed high expression in lung tumor tissue and null expression in RNA from benign LNs.

Results: Thirteen per cent of the LNs were positive for CEACAM5 and 16% for PLUNC. Eight of 38 NSCLC patients had positive expression in pN2 nodes by CEACAM5 and/or PLUNC and disease-free survival (P = 0.028) and overall survival time was significantly worse in these patients compared with those with negative expression (P = 0.0083).

Conclusions: Quantitative real-time RT-PCR of CEACAM5 and PLUNC can estimate the presence of micrometastatic cells in LNs with greater precision than current staging method used for assessing tumor recurrence risk.

adjuvant therapy, disease progression, NSCLC, occult micrometastases, prognosis, quantitative real-time RT-PCR

{dagger} Present address: USP Instituto Universitario Dexeus, Pangaea Biotech, Laboratorio Oncología, Sabino Arana 5, 08028, Barcelona, Spain.

Received for publication May 14, 2008. Revision received June 30, 2008. Accepted for publication July 1, 2008.


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