The P2X₇ receptor: A novel biomarker of uterine epithelial cancers

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 P2X ₇ 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.