This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, X. Articles by Gorodeski, G. I. Search for Related Content PubMed PubMed Citation Articles by Li, X. Articles by Gorodeski, G. I. Related Collections Early Detection Early Detection: Biomarkers: Discovery, Methodology, Validation

The P2X₇ Receptor: A Novel Biomarker of Uterine Epithelial Cancers

Departments of ¹ Reproductive Biology, ² Pathology, ³ Oncology, and ⁴ Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio and ⁵ Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland

Requests for reprints: George I. Gorodeski, University MacDonald Women's Hospital, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106. Phone: 216-844-5977; Fax: 216-983-0091. E-mail: gig{at}cwru.edu.

Objective: To determine expression of the P2X₇ receptor in normal and in cancer uterine tissues. The rationale was that the receptor P2X₇ regulates constitutive apoptosis in uterine epithelial cells, and previous studies showed diminished P2X₇-mediated apoptosis in cancer uterine cells compared with normal cells.

Methods: A clinical, experimental feasibility study. Normal (n = 42) and cancer uterine tissues (n = 47) were obtained from a total of 72 women ages 25 to 75. End points for P2X₇ mRNA were quantitative PCR and in situ hybridization, and end points for P2X₇ protein were Western blots and immunostaining using anti-P2X₇ antibody.

Results: (a) In normal uteri, P2X₇ mRNA and protein were expressed predominantly in the epithelial (endometrial, endocervical, and ectocervical) cells. (b) Expression of the P2X₇ mRNA and protein was absent from endometrial and endocervical adenocarcinoma tissues and from cervical squamous cell carcinoma tissues. (c) In cervical dysplasia, P2X₇ protein was absent in the dysplastic lesions. (d) Semiquantitative analysis using P2X₇ mRNA (normalized in each tissue to the constitutive glyceraldehyde-3-phosphate dehydrogenase) and P2X₇ protein levels (normalized in each tissue to the constitutive tubulin) revealed that P2X₇ mRNA and/or protein levels can distinguish uterine normal from cancer tissues at high degrees of sensitivity (92%, 100%) and specificity (100%, 90%).

Summary and Conclusions: (a) Levels of the P2X₇ are lower in uterine epithelial cancer tissues than in the corresponding normal tissues. (b) The data suggest that tissue P2X₇ mRNA and protein levels could be used as a novel biomarker to differentiate normal and cancer uterine epithelial tissues. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1906–13)