Prognostic significance of topoisomerase II alpha and collagen IV immunoexpression in cervical cancer.
OBJECTIVE
The immunohistochemical (IHC) expression of topoisomerase II alpha and collagen IV was studied in cervical cancer. The results of IHC expression for both markers were compared to the clinical and histological factors predicting the course of disease.


METHODS
In 114 patients with cervical cancer, treated at the Department of Gynecology and Obstetrics, University Medical Centre Ljubljana between 1995 and 1999, the tumor tissue was analyzed using standard IHC staining (IHS) procedures for topoisomerase II alpha and collagen IV. The obtained results were compared to those obtained by clinical, pathomorphological and morphometric prognostic factors, and the impact of the analyzed factors on the outcome of disease was assessed.


RESULTS
A high percentage of IHC expression of topoisomerase II alpha was present in 55.3%, and to collagen IV in 28.1% of cervical cancer patients. In the multivariate analysis the IHS intensity to collagen IV was significantly associated with lymphovascular invasion (OR = 5.906; 95% CI 2.18-15.96). Kaplan-Meier analysis showed a statistically significantly better survival in initial cervical cancer stages (p = 0.001), in tumors with a higher degree of differentiation (p = 0.049), more shallow depth of invasion (p = 0.004), smaller horizontal tumor spread (p = 0.001), in cases with no lymph node metastases (p = 0.001) and no lymphovascular space invasion (p = 0.001), in younger age groups (p = 0.001) and in women with regular menstrual cycles (p = 0.001).


CONCLUSIONS
IHC expression of topoisomerase II alpha and collagen IV was significantly correlated with defense reaction. A negative and weak IHC to collagen IV was a statistically significant independent predictive variable for lymphovascular invasion, related to metastatic spread in the lymph nodes. The two analyzed IHC markers indicate the existence of factors at the molecular level that might complement the assessment of cervical cancer prognosis, resulting in the appropriate choice of type and extent of treatment.
Smrkolj
S
S
Department of Gynecology and Obstetrics, University Medical Centre Ljubljana, Slovenia. spela.smrkolj@mf.uni-lj.si
Erzen
M
M
Rakar
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis*; D024141:Collagen Type IV / Q000032:analysis*; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology
D000951:Antigens, Neoplasm; D024141:Collagen Type IV; D004268:DNA-Binding Proteins; D007797:Laminin; D004250:DNA Topoisomerases, Type II