Prognostic significance of the Fas-receptor/Fas-ligand system in cervical squamous cell carcinoma.
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.
Lerma
Enrique
E
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. elerma@santpau.es
Romero
Marisa
M
Gallardo
Alberto
A
Pons
Cristina
C
Muñoz
Josefina
J
Fuentes
Josefina
J
Lloveras
Belen
B
Catasus
Lluis
L
Prat
Jaime
J
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000821:virology; D015344:DNA Probes, HPV; D004279:DNA, Viral / Q000302:isolation & purification; D018572:Disease-Free Survival; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology; D019014:fas Receptor / Q000378:metabolism*
D014408:Biomarkers, Tumor; D015344:DNA Probes, HPV; D004279:DNA, Viral; D053222:Fas Ligand Protein; D019014:fas Receptor