Expression of thrombospondin-1 in conjunctival squamous cell carcinoma is correlated to the Ki67 index and associated with progression-free survival

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 259; no. 10; pp. 3127 - 3136
• Main Authors: Tagami, Mizuki, Kakehashi, Anna, Sakai, Atsushi, Misawa, Norihiko, Katsuyama-Yoshikawa, Atsuko, Wanibuchi, Hideki, Azumi, Atsushi, Honda, Shigeru
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2021; Springer Nature B.V
• Subjects: Cancer; Carcinoma, Squamous Cell - genetics; Gene expression; Humans; Immunohistochemistry; Intracellular; Ki-67 Antigen - genetics; Localization; Medical prognosis; Medicine; Medicine & Public Health; Neoplasm Recurrence, Local; Oncology; Ophthalmology; Prognosis; Progression-Free Survival; Retrospective Studies; Squamous cell carcinoma; Thrombospondin; Thrombospondin 1 - genetics; Tumor cells; Tumors; Thrombospondin-1; Immunohistochemistry; Conjunctival squamous cell carcinoma; Ki67 index; Asian population
• DOI: 10.1007/s00417-021-05236-7
• ISSN: 0721-832X

Purpose Conjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to investigate thrombospondin-1 expression and its association with prognosis. Methods In this retrospective study, a gene expression array along with immunohistochemistry were performed for the evaluation of thrombospondin-1 expression, localization, as well as Ki67 labeling cell indices in carcinoma in situ (Tis) and advanced conjunctival SCC (Tadv). The presence or absence and intensity of cytoplasmic and nuclear staining in tumor cells were also divided into groups with a score of 0–3 and semi-quantitatively analyzed to investigate intracellular staining patterns. The association between thrombospondin-1 expression and tumor progression in a series of 31 conjunctival SCCs was further investigated. Results All 31 patients in the cohort (100%) were East Asian. A simple comparison between Tis and Tadv demonstrated significant differences in expressions of 45 genes, including thrombospondin-1 ( p  < 0.01). In this cohort, 30/31 tumors were positive (96%) for thrombospondin-1. Furthermore, thrombospondin-1 intracellular staining pattern analysis scores were 2.12 and 0.96 for nuclear and cytoplasmic staining, respectively, with a significant difference observed between Tis and Tadv ( p  < 0.01). Alteration of the Ki67 labeling index was significantly correlated with that of the thrombospondin-1 cytoplasmic score ( p  = 0.030). Furthermore, univariate Cox regression analysis showed a significant correlation between thrombospondin-1 staining and progression-free survival ( p  = 0.026) and final orbital exenteration ( p  = 0.019). Conclusions The present results demonstrated that thrombospondin-1 is a potential molecular target in the pathology of conjunctival SCC, in addition to serving as a prognostic factor.