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Carcinoembryonic antigen mRNA analysis detects micrometastatic cells in blood from lung cancer patients

¹ Dipartimento di Biochimica e Biotecnologie Mediche and CEINGE-Biotecnologie Avanzate scarl, ² Cattedra di Malattie dell'Apparato Respiratorio, Facoltà di Medicina, Università di Napoli "Federico II", and ³ Facoltà di Scienze Matematiche, Fisiche e Naturali, Università del Molise, Isernia, Italy

CORRESPONDENCE: F. Salvatore, Dipartimento di Biochimica e Biotecnologie Mediche, via S. Pansini 5, 80131, Naples, Italy. Fax: 39 0817463650. E-mail: salvator@unina.it

Keywords: aldolase A, carcinoembryonic antigen, cytokeratin 19 and 20, epithelial glycoprotein 2, micrometastases

Received: November 29, 2002
Accepted April 15, 2003

Grants from Ministero Italiano dell'Università e della Ricerca (MIUR; Rome, Italy); from the Consiglio Nazionale delle Ricerche (CNR) Targeted project "Biotecnologie"; and from Regione Campania (Ricerca Sanitaria Finalizzata and L.R. 41/96) are gratefully acknowledged.

The current authors previously identified circulating cells expressing carcinoembryonic antigen (CEA) messenger ribonucleic acid (mRNA) in 80% of lung cancer patients bearing distant metastases. The current study prospectively validated the data on a novel cohort and extended the study to other mRNAs expressed by neoplastic cells.

CEA, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 (EPG2) mRNA was analysed by reverse transcriptase-polymerase chain reaction in circulating cells from 19 healthy controls, and in biopsies and blood at diagnosis from 32 lung cancer patients monitored for 24 months.

Aldolase A and cytokeratin 19 mRNA occurred in circulating cells of all controls; cytokeratin 20 was not expressed by any lung cancer biopsy. EPG2 mRNA occurred in all biopsies but not in the patients' circulating cells. CEA mRNA occurred in 29/32 (90.6%) biopsies and in 17/32 mRNA samples from circulating cells from lung cancer patients. Of these positive patients 12/17 developed metastases within 9 months of mRNA analysis. Three positive patients died, one was lost to follow-up, and one did not develop metastases within 24 months. Of the negative patients 12/15 did not develop metastases during the 24-month follow-up; one patient was lost to follow-up, one did not express CEA, and another developed metastases.

Unlike in other neoplasias, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 messenger ribonucleic acid are not useful for the detection of circulating cancer cells in lung cancer. Carcinoembryonic antigen messenger ribonucleic acid analysis in circulating cells helps to identify lung cancer patients at a greater risk of metastases.

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