Identification of cripto-1 as a novel serologic marker for breast and colon cancer.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
This study suggests that plasma CR-1 might represent a novel biomarker for the detection of breast and colon carcinomas.
Bianco
Caterina
C
Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Strizzi
Luigi
L
Mancino
Mario
M
Rehman
Aasia
A
Hamada
Shin
S
Watanabe
Kazuhide
K
De Luca
Antonella
A
Jones
Brenda
B
Balogh
Gabriela
G
Russo
Jose
J
Mailo
Daniel
D
Palaia
Raffaele
R
D'Aiuto
Giuseppe
G
Botti
Gerardo
G
Perrone
Francesco
F
Salomon
David S
DS
Normanno
Nicola
N
D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D003110:Colonic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human; D004815:Epidermal Growth Factor