Stratifin as a Prognostic Marker in Ocular Surface Squamous Neoplasia
Sheetal Chauhan, Seema Sen, Anjana Sharma, Shyam S Chauhan, Seema Kashyap, Neelam Pushker, M Vanathi, Radhika Tandon, Rajvardhan Azad. All India Institute of Medical Sciences, New Delhi, India; AIIMS, New Delhi, India
Background: Ocular surface squamous neoplasia (OSSN) is the most common tumour of ocular surface with an incidence of 0.02 to 3.5 per 100,000. It encompasses spectrum of lesions ranging from dysplasia to squamous cell carcinoma (SCC). Stratifin (14-3-3σ)/HEM (human epithelial marker) which is an inhibitor of cell cycle progression, is a target of epigenetic deregulation in many carcinomas. However, its role in OSSN has not been investigated. In the present study, the association of stratifin expression with its promoter methylation status and their correlation with clinicopathological features in ocular surface squamous neoplasia patients was evaluated.
Design: Sixty four cases of histopathologically confirmed OSSN (44 SCC and 20 dysplasia) were included in this study. Each tumour was staged according to the AJCC TNM criteria. Immunohistochemistry and methylation specific PCR were used to evaluate expression of stratifin protein and its methylation status. Prognostic significance was assessed using Kaplan–Meier survival and Cox regression analysis.
Results: Loss of stratifin immunoexpression was observed in 75% cases (48/64) and promoter hypermethylation in 62.5% (40/64) cases of OSSN. Stratifin promoter hypermethylation was significantly associated with loss of its immunoexpression (38/40) (P=<0.0001). On correlation with clinical parameters, both loss of Stratifin immunoexpression and methylation were significantly associated with recurrence, tumor size ≥2cm (higher T category), orbital or intraocular invasion and reduced disease free survival (P≤0.05). Cox analysis showed stratifin to be an independent prognostic factor for OSSN (p =0.03).
Conclusions: Our results indicate that loss of Stratifin expression occours in OSSN and is caused by aberrant DNA methylation. Further, this loss of stratifin immunoexpression could prove to be a useful poor prognostic marker in OSSN patients after further validation.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 268, Monday Morning