Prognostic significance of the Fas-receptor/Fas-ligand system in cervical squamous cell carcinoma.

ABSTRACT

We studied whether Fas-receptor (Fas-R; CD95) expression, single-nucleotide polymorphisms (SNPs) in the Fas promoter region, and/or Fas-ligand (Fas-L) production could determine individual susceptibility to cervical cancer progression. The clinicopathologic features of 38 patients with cervical squamous carcinomas (22 stage I, 8 stage II, and 8 stage III+) were reviewed and related with (a) Fas-R expression by immunohistochemistry; (b) Fas-R SNPs at -670 and -1377 locations by restriction fragment length polymorphism and DNA sequencing; and (c) Fas-L expression by immunohistochemistry. Overall and disease-free survival curves showed significant differences in relation to stage (p < 0.001). Fas-R was identified in 20 of 38 (52.6%) tumors without statistical differences in survival, stage, or Fas-L overproduction. Fas-R GG genotype was more common than expected in advanced tumors (p = 0.065). The Fas-R-1377A allele and AA genotype were unrelated with survival, stage, or Fas-R expression. Fas-L overproduction was detected in 20 of 38 (52.6%) tumors; it was more frequent in advanced-stage tumors and was inversely related to survival (p = 0.03) and decrease in host inflammatory response (p = 0.01). Fas-R expression by tumor cells seems unrelated to stage or lymphoid infiltrate. Tumor production of Fas-L may represent an attempt to destroy the host's lymphocytic reaction.