P16INK4a In Oular Surface Squamous Neoplasia | 12183
Journal of Biotechnology & Biomaterials
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Ocular Surface Squamous Neoplasia (OSSN) is the most common tumour of ocular surface and encompasses both conjunctival
intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). p16INK4a is a tumor suppressor protein, Its inactivation
by aberrant methylation of CpG islands is frequent in various cancers. Sixty-four cases of OSSN and 15 normal conjunctival
controls were included in this study. Immunohistochemistry and Methylation specific PCR was used to evaluate expression of
p16INK4a protein and its methylation status. Follow-up data (16 to 36 months) was available in 48 (75%) cases.
Loss of p16INK4a immunoexpression was observed in 72% cases (48) and promoter hypermethylation in 53% (34). P16INK4a
promoter hypermethylation showed significant association with immunoexpression(P=<0.0001). Hypermethylation of p16INK4a
was not however associated significantly with any clinicopathological features or survival.
p16INK4a Overexpression was observed in 18 (28%) OSSN and was absent in all control conjunctival tissues. p16INK4a positive
cases belonged to younger age group (P=0.03), had higher T stage (P=0.007), larger tumour size (P=0.04) and invasive SCC
(P=0.03). Its expression was seen in all the cases with metastasis (6/6) (P= 0.0002) and death (4/4) (P= 0.004). Although in our
study disease free survival was worst in p16INK4a positive cases, the difference was not statistical significant (P=0.09).
Loss of p16INK4a expression is frequent in OSSN cases and is caused by aberrant DNA methylation. Overexpression of p16INK4a
is a useful indictor of aggressive disease and suggests alteration in pRb pathway in this subset of tumors which may play an
important role in the pathogenesis and progression of OSSN.
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