EXPRESSION OF EPITHELIAL CADHERIN AND P16INK4 IN HIGH RISK HUMAN PAPILLOMA VIRUS INFECTION OF CERVICAL INTRAEPITHELIAL LESION IN ATTENDEES OF NNAMDI AZIKIWE UNIVERSITY TEACHING HOSPITAL, NNEWI, ANAMBRA STATE, NIGERIA.
Keywords:
Cervical intraepithelial lesions, LSIL, HSIL, immunohistochemistry, E.cadherin, P16INK4a protein expressionAbstract
Reduced expression of E.cadherin is regarded as one of the main molecular events in dysfunction of the cell adhesion system, triggering cancer invasion and metastasis and disrupt cell cycle regulation. Loss of cell cycle regulation is main event in cancer. P16INK4 is a well known surrogate marker for hr-HPV infection. Hence, there is need to determine the role of E.cadherin, in progression of high –risk human papilloma virus (hr-HPV) infection in uterine cervix. The aim of this study was to determine expression pattern of E.cadherin and P16INK4a their role in progression of high-risk HPV type of cervical intraepithelial neoplasm or lesions (CIN/CILs) in attendees of Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria. Eighty-six (86) cases of cervical squamous intraepithelial lesion (cSIL) were included in the study. Immunohistochemistry was performed on both test and control lesions for E.cadherin and P16 protein. The immunoreactivity were evaluated for each marker and the values were statistically analysed. Out of the 86 cases of CILs subjected to E.cadherin and P16INK4a monoclonal antibodies, 55.8% (48/86 cases) had an initial, pre-immunohistochemical diagnosis as CIN 1 (Low-grade squamous intraepithelial lesion; LSIL) while 44.2% (38/86cases) were high-grade squamous intraepithelial lesions (HSIL). However, on application of monoclonal antibodies of E.cadherin, and P16, majority of LSIL had a change of diagnosis to Negative squamous intraepithelial lesions (NSIL) 21/48 (43.8%) and chronic cervicitis 11/48 (27.1%) while 16/48 cases (35.4%) were finally retained as LSIL. Of 38 initially diagnosed as HSIL lesions {CIN2, CIN3, and Carcinoma In-situ; (CIS) 35 cases (92.1%) were concordant with previous diagnosis while three cases were regrouped as CIN 1 (one case) and chronic cervicitis (2 cases). Therefore, the total number of CIN 1 was 17 cases and chronic cervicitis were 13 cases. The rate of E.cadherin, P16INK4a expression in non neoplastic and LSIL lesion were; 85.3% and 100% respectively; In HSIL the rate of the E.cadherin cytoplasmic and P16INK4a expression increased with the increased degree of dysplasia, from 70% in CIN2 to 87.5% and CIN3 to 88.9% in CIS. The rate of the E.cadherin cytoplasmic expression positively correlated with diffuse p16 positive expression in HSIL.
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