Immunohistochemical Overexpression of p16 Protein Associated with Cervical Cancer in Thailand


Cervical cancer is caused by persistent infections through “high risk (HR) types” of human HPVs, particularlyHPV 16 and 18. HR-HPV types encode two potent oncogenes, referred to as E6 and E7. Both are required toinduce and maintain neoplastic growth of cervical cancer cells. Cyclin dependent kinase inhibitor genes as forexample p16INK4A were shown to be negative regulated by active pRb. Inactivation of pRb by E7 thus releasesthe p16 gene from its negative transcriptional control and results in significant overexpression of p16 encodedprotein in HPV transformed cells. It has been demonstrated that p16 protein can be detected in cervicalpreneoplasia all high grade SIL or invasive cancers, whereas no expression was detected in normal, metaplasticor inflammatory cervical lesions. Moreover, low grade cervical lesions induced by low risk HPV infection buthistological indistinguishable from low grade lesions induced by HR-HPV-infections could be clearly differentiatedby p16INK4A immunohistochemistry, showing negative staining for p16 protein. The objective of this study isto examine the expression of p16 protein in cervical carcinoma in Thailand. Immunohistochemical analysis ofp16INK4A was performed on 53 formalin – fixed and paraffin – embedded samples of various stages of cervicalneoplastic lesions. There are squamous cell carcinoma in situ 8 cases, squamous cell carcinoma in situ withglandular involvement 16 cases, microinvasive squamous cell carcinoma 13 cases and invasive squamous cellcarcinoma 16 cases. The specimens were taken from cervical biopsy, cervical conization and hysterectomy in theyear 2000 at National Cancer Institute. Strong immunoreactivity for the p16 protein was observed in only thenuclei and cytoplasm of all cervical neoplastic cells. This study supported the idea that immunohistochemicaloverexpression of the p16 protein may be a useful screening test for cervical cancer. In addition, p16immunohistochemistry is useful for helping in the interpretation of cervical histology samples, facilitating morerapid diagnosis.