Predicting the outcome of squamous cell carcinoma of the uterine cervix using combinations of individual tumor marker expressions.
OBJECTIVE
To evaluate if combining the individual expression patterns of biomarkers targeting different molecular alterations in tumor development will improve prognosis prediction in invasive squamous cell carcinoma of the uterine cervix.


METHODS
Ten-year follow-up results in 128 women with cervical cancer were compared to the expression of 10 relevant tumor markers, assessed with immunohistochemistry. The markers were selected to represent cell proliferation, tumor suppression, cell-cell adhesion, angiogenesis, apoptosis, inflammation and immune response. All analyses were adjusted for stage.


RESULTS
p53 expression, and low expression of c-myc and COX-2 correlated significantly with survival. In addition CD4+ expression was included in the analyses of combinations. When these four tumor markers were combined, two-by-two, ten combinations correlated significantly with 10-year survival. The overall 10-year survival rate with a low COX-2 and a high CD4+ expression was 76% versus 53% in the remaining women (odds ratio 3.73, 95% CI 1.42-11.0). The survival rate with absent p53 and high COX-2 expression in the tumors was 42% versus 71% (odds ratio 0.25, 95% CI 0.10-0.37), while the corresponding figures for the combination of high COX-2 intensity and expression of c-myc were 27% versus 62% (odds ratio 0.13, 95% CI 0.02-0.52). None of the single markers correlated significantly with outcome in the final Cox regression analyses, while five combinations did.


CONCLUSIONS
Combinations of selected, biologically plausible tumor markers might be more useful for predicting the outcome than using single markers.
Lindström
Annika K
AK
Ventrum Clinic, Bjursås, Sweden. ventrum@telia.com
Stendahl
Ulf
U
Tot
Tibor
T
Lidström
Bo-Marcus
BM
Hellberg
Dan
D
D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000401:mortality*
D014408:Biomarkers, Tumor