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

Tagami, Mizuki; Kakehashi, Anna; Sakai, Atsushi; Misawa, Norihiko; Katsuyama-Yoshikawa, Atsuko; Wanibuchi, Hideki; Azumi, Atsushi; Honda, Shigeru

doi:10.1007/s00417-021-05236-7

Cited by 4 publications

(3 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There was a significant difference between the Tis and Tadv groups. Increased expression of CXCR4 in the Tadv group was also confirmed by both immunohistochemical analysis and our previous analysis of mRNA expression [ 24 ].…”

Section: Discussionsupporting

confidence: 75%

See 1 more Smart Citation

FOXP3 and CXCR4-positive regulatory T cells in the tumor stroma as indicators of tumor immunity in the conjunctival squamous cell carcinoma microenvironment

et al. 2022

Self Cite

View full text Add to dashboard Cite

Conjunctival squamous cell carcinoma (SCC) is the most common ocular surface neoplasia. The purpose of this retrospective study was to examine the role of regulatory T cell (Treg) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. Cancer progression gene array and immunohistochemical analyses of FOXP3 as a Treg marker, CD8 as a tumor-infiltrating lymphocyte marker, and CXCR4 expression on activated Tregs were conducted in a series of 31 conjunctival SCC cases. The objective was to investigate the immunoreactive response in tumor cells and stromal cells in the cancer microenvironment. The stroma ratio in tumor cells was investigated by monitoring α-smooth muscle actine (SMA) expression between carcinoma in situ (Tis) and advanced carcinoma (Tadv) (P<0.01). No significant change in PD-L1 expression was observed in this study (P = 0.15). Staining patterns of FOXP3, CD8, and CXCR4 were examined separately between tumor cells and stromal cells in SCC tumors. Differences in staining of FOXP3 in Tregs and CD8 in tumor-infiltrating lymphocytes in tumor stroma in the Tis group were observed compared with the Tadv group (each P<0.01). In addition, double immunostaining of CXCR4/FOXP3 was correlated with progression-free survival (P = 0.049). Double immunostaining of CXCR4/FOXP3 correlated with American Joint Committee on Cancer T-stage, independent of age or Ki67 index (P<0.01). Our results show that FOXP3 and the CXCR4/FOXP3 axis are important pathologic and prognostic factors of ocular surface neoplasia, including SCC. The tumor microenvironment of conjunctival SCC should be considered in the future development of treatment options.

show abstract

Section: Discussionsupporting

confidence: 75%

“…Expression of mRNA for CXCR4 , HIF-1α , IL-6 , NFKB1 , and ROCK1 differed significantly ( P <0.05) between the Tis and Tadv groups. We have already published some of these results [ 24 ]. the multiple correction test was also performed by the Benjamini-Yekutieli method, however in that case were no significant difference (P <0.05).…”

Section: Resultsmentioning

confidence: 99%

FOXP3 and CXCR4-positive regulatory T cells in the tumor stroma as indicators of tumor immunity in the conjunctival squamous cell carcinoma microenvironment

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“… 17 In an East Asian cohort of 31 patients, transcriptomic comparison between carcinoma in situ and advanced disease revealed significant differences in the expression of 45 genes, with thrombospondin-1 ( THBS1 ) being the most biologically important. 18 In a study of 41 Ugandan patients, TP53 codon 72 polymorphisms were found to be an independent risk factor for high-grade conjunctival intraepithelial neoplasia and invasive conjSCC, regardless of HIV status. 19 In a report from Saudi Arabia, TP53 overexpression was found in 14 of 23 (61%) conjSCCs and correlated with poor clinical outcome.…”

mentioning

confidence: 99%

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden

Gleber-Netto,

Nagarajan,

Sagiv

et al. 2024

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies. Methods We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas. Results Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. Conclusions Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.

show abstract

Conjunctiva

Yanoff,

Sassani

2025

Ocular Pathology

View full text Add to dashboard Cite

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

Cited by 4 publications

References 29 publications

FOXP3 and CXCR4-positive regulatory T cells in the tumor stroma as indicators of tumor immunity in the conjunctival squamous cell carcinoma microenvironment

FOXP3 and CXCR4-positive regulatory T cells in the tumor stroma as indicators of tumor immunity in the conjunctival squamous cell carcinoma microenvironment

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden

Conjunctiva

Contact Info

Product

Resources

About