Abstract 5155: Status and clinical relavence of G1/S cell cycle regulatory proteins in Ocular Surface Squamous Neoplasia

Abstract

Abstract Purpose: Ocular Surface Squamous Neoplasia (OSSN) is a common tumour of ocular surface arising from the limbus, cornea or conjunctiva. It includes conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). Although confined to ocular surface, they have capability to recur (5-53%), metastasize (0-16%) and even cause death (8%).One of the most important issues still unresolved in the treatment and management of OSSN is the inability to determine factors causing disease progression. Identification of reliable biomarkers which could detect progression as well as identify high risk cases is an urgent necessity. The Cyclin D1/p16INK4a/pRb pathway plays a critical role in tumorigenesis and alterations in these proteins have been reported in various malignancies. This study was designed to explore the status of pRb, p16INK4a and cyclin D1 in various clinical stages of OSSN patients. Methods:Sixty-four histopathologically confirmed OSSN cases (44 squamous cell carcinomas and 20 conjunctival intraepithelial neoplasias) were included in this study. AJCC TNM staging was done and patients were followed up for 36 to 58 months (median 46 months). Immunohistochemical expression of total pRb (clone-13A10), phosphorylated Rb (clone-Phospho-Ser780), p16INK4a (clone-6H12), and cyclin D1 (clone-SP4) protein was evaluated. Kaplan-Meier survival and Cox regression analysis was done to assess the prognostic significance of these proteins. Results: Immunoexpression of the targeted proteins demonstrated loss /inactive form of pRb in 87% OSSN cases, p16INK4a and cyclin D1 overexpression in 28% in 63% cases respectively. From T1 to T3 AJCC category there was a progressive increase of p16INK4a (0%in T1 to 100% in T3) (P = 0.007) and cyclin D1 overexpression (25% in T1 to 88% in T4). Loss of pRb (75% in T1 to 100% in T4) (P = 0.03) was also seen. Loss of pRb expression was the earliest change which was detected in 75% cases in T1.The Kaplan Meier survival curves revealed loss of pRb (P = 0.0002, log rank analysis) as well as p16INK4a(P = 0.11, log rank analysis) and cyclin D1 over expression (P = 0.06, log rank analysis) adversely affected the disease free survival. pRb loss however emerged as the single most sensitive poor prognostic indicator in all AJCC stages of OSSN patients. Conclusion: G1/S cell cycle proteins (retinoblastoma, p16INK4aand cyclin D1) have prognostic relevance in OSSN patients. Of these pRb loss is the most useful indicator of aggressive behavior and is therefore recommended for detecting high risk OSSN patients. The dysregulation of p16INK4a, cyclin D1 and pRb proteins also plays an important role in pathogenesis of OSSN patients. Note: This abstract was not presented at the meeting. Citation Format: Sheetal Chauhan, Seema Sen, Anjana Sharma, Seema Kashyap, M. Vanathi, Neelam Pushker, Radhika Tandon. Status and clinical relavence of G1/S cell cycle regulatory proteins in Ocular Surface Squamous Neoplasia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5155. doi:10.1158/1538-7445.AM2015-5155