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Prisca Raquel Bustamante, Jade Marie Lasiste, Denise Miyamoto, sabrina bergeron, Christina Mastromonaco, Laura Nuñez, Miguel N Burnier; CD109: a novel marker for Ocular Surface Squamous Neoplasia differentiation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5596.
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CD109 is a transmembrane protein that binds to TGF-β and inhibits TGF-β/Smad signaling. CD109 expression has been detected predominantly in squamous cell carcinoma (SCC) and its expression is higher in well-differentiated tumors. Ocular surface squamous neoplasia (OSSN) encompasses a spectrum of precancerous and malignant lesions of the conjunctiva. OSSN ranges from dysplasia to conjunctival intraepithelial neoplasia (CIN) I (mild), II (moderate) or III (severe), to SCC which is the most frequent malignancy of the conjunctiva. The aim of this study is to evaluate CD109 expression in OSSN to determine if its presence is related to spectrum progression.
Automated immunohistochemistry using anti-CD109 was performed in 20 OSSN case series: CIN I-II (n=9), CIN III (n=5), SCC (n=6), and normal epithelium (NE; n=5). Cutaneous melanomas were used as a positive control. Slides were analyzed using Aperio Positive Pixel Count algorithm. In addition, an ocular pathologist manually evaluated positivity based on a scale from 0 to 2 (0=negative, 1=mild, 2=intense). Staining extent was classified as 1=focal or 2=diffuse. Extent and intensity were converted to the German Immunoreactive Score; a score 2 or higher was considered positive. Statistical analysis was performed using Mann-Whitney and Fisher exact test; P<0.05 was considered significant.
CD109 positivity was detected in all OSSN cases. Expression in OSSN was statistically higher than in NE (P=0.0008). Using the automated software, expression was significantly greater in all lesions (CIN I-II [P=0.001], CIN III [P=0.007], SCC [P=0.043]) compared to NE. According to the manual analysis, there was a statistically significant difference in CIN I-II (P=0.005), CIN III (P=0.04) and SCC (P=0.454) compared to NE. No significant differences in expression between CIN I-II vs CIN III or SCC were found. No correlation between age and CD109 expression was found (r=0.152).
To the best of our knowledge, this is the first study assessing expression of CD109 in OSSN. The similar results obtained using both software and manual evaluation validates the automated analysis. CD109 upregulation suggests an involvement in the pathogenesis of OSSN. Further studies are necessary to investigate the role of CD109 in the progression of CIN to SCC in the conjunctiva and as a possible therapeutic target.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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