Significance of topoisomerase IIIβ expression in breast ductal carcinomas: strong associations with disease-specific survival and metastasis.
Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase IIIβ, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase IIIβ in breast cancer and its relationships with clinicopathologic features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase IIIβ, estrogen receptor, progesterone receptor, HER-2, BRCA-1, p53, and Ki67. Immunostaining for topoisomerase IIIβ was found in 33.9% of breast carcinomas, and immunopositivity was correlated with distant metastasis (P = .036) and death (P = .006). Decreased expression of topoisomerase IIIβ correlated with low expression of Ki67 (P < .001) and negativity for HER-2 (P < .001), BRCA-1 (P = .001), and p53 (P < .001). In the multivariate analysis, topoisomerase IIIβ expression was a significant predictor of survival (hazard ratio, 3.006 [95% confidence interval, 1.582-5.715]; P = .001). In conclusion, topoisomerase IIIβ expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival.
Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil.
João Paulo
JP
Oliveira-Costa
Juliana
J
Zanetti
Lucinei Roberto
LR
Oliveira
Fernando Augusto
FA
Soares
Leandra Zambelli
LZ
Ramalho
Fernando
F
Silva Ramalho
Sérgio Britto
SB
Garcia
Alfredo
A
Ribeiro-Silva
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001938:Brazil / Q000453:epidemiology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D003131:Combined Modality Therapy; D020732:Cytogenetic Analysis; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D055815:Young Adult
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D004264:DNA Topoisomerases, Type I