The expression of P16INK4a in cervical intraepithelial neoplasia and invasive carcinoma

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Klin Onkol 2003; 16(6): 249-252.

Abstract:
Background: The antioncogene p16INK4a inhibits cyclin-dependent kinases and represents a feedback regulation of the cell cycle. Protein Rb, the product of the retinoblastoma antioncogene, in its active form inhibits transcription of p16. In dysplasias and carcinomas of the uterine cervix the papilomaviruses transform the epithelium by inactivation of the pRb by oncoprotein E7, among others. Due to pRb inactivity the level of p16 protein in cells is increased.
Patients and Methods: An immunohistochemical analysis of 56 cases of formalin-fixed, paraffin embedded samples of the uterine cervix (included cone biopsies and hysterectomies) was performed. The database included 10 cases of CIN I-II, 30 cases of CIN III, 8 invasive squamous cell carcinomas, 2 cases of endocervical adenocarcinoma and 6 cases of reactive epithelial changes. The imunoblotting of p16 was performed in cell lines with known function of Rb.
Results: Diffuse and intensive positivity was found in all cases of CIN III and squamous cell carcinomas. Cases of the CIN I-II were partially positive in 7 cases and positivity was found in one adenocarcinoma. In cell lines, the p16 expression was restricted to cells with impaired Rb (HeLa and HS913T).
Conclusion: Our study confirmed increased expression of p16INK4a in high-grade precancerous lesions and in carcinomas of the uterine cervix. The detection of p16 seems to be valuable tool in the surgical pathology of the uterine cervix: possible evaluation of the surgical margins, the differential diagnosis regarding reactive atypia, and it is also perspective in oncocytologic diagnosis regarding differential diagnosis of the ASCUS, or possibly can be used in automated screening or quality assessment.

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