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Identification of Cripto-1 as a Novel Serologic Marker for Breast and Colon Cancer

Authors' Affiliations: ¹ Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, NIH, Bethesda, Maryland, ² Department of Molecular and Cellular Biology, University of Michigan, Ann Arbor, Michigan, ³ Cell Biology and Preclinical Models Unit, ⁴ Surgical Oncology C Unit, ⁵ Surgical Oncology A Unit, ⁶ Pathology Unit, and ⁷ Clinical Trials Unit, ITN-Fondazione Pascale, Naples, Italy, and ⁸ Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, Pennsylvania

Requests for reprints: David S. Salomon, Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Building 37, Room 1108B, Bethesda, MD 20892. Phone: 301-496-9536; Fax: 301-402-8656; E-mail: salomond{at}mail.nih.gov. Nicola Normanno, Cell Biology and Preclinical Model Units, ITN-Fondazione Pascale, Naples, Italy, 80131. Phone and Fax: 081-5903826. E-mail: nicnorm{at}yahoo.com.

Purpose: Human Cripto-1 (CR-1), a cell membrane glycosylphosphatidylinositol-anchored glycoprotein that can also be cleaved from the membrane, is expressed at high levels in several different types of human tumors. We evaluated whether CR-1 is present in the plasma of patients with breast and colon cancer, and if it can represent a new biomarker for these malignancies.

Experimental Design: We determined CR-1 plasma levels using a sandwich-type ELISA in 21 healthy volunteers, 54 patients with breast cancer, 33 patients with colon carcinoma, and 21 patients with benign breast lesions. Immunohistochemical analysis was also used to assess CR-1 expression in cancerous tissues.

Results: Very low levels of CR-1 (mean ± SD) were detected in the plasma of healthy volunteers (0.32 ± 0.19 ng/mL). A statistically significant increase in the levels of plasma CR-1 was found in patients with colon carcinoma (4.68 ± 3.5 ng/mL) and in patients with breast carcinoma (2.97 ± 1.48 ng/mL; P < 0.001). Although moderate levels of plasma CR-1 were found in women with benign lesions of the breast (1.7 ± 0.99 ng/mL), these levels were significantly lower than in patients with breast cancer (P < 0.001). Finally, immunohistochemical analysis and real-time reverse transcription-PCR confirmed strong positivity for CR-1 in colon and/or breast tumor tissues.

Conclusion: This study suggests that plasma CR-1 might represent a novel biomarker for the detection of breast and colon carcinomas.

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