c-erbB-2, p53, and nm23 proteins as prognostic factors in patients with epithelial ovarian carcinoma.
OBJECTIVE
To demonstrate immunohistochemical expression of p53, c-erbB-2, and nm23 proteins in ovarian cancer and to establish their correlation with such predictive factors as clinical stage, grade, and vascular invasion. The effect of protein overexpression on patients' overall survival was also assessed.


METHODS
We performed immunohistochemical analysis of formalin-fixed, paraffin-embedded specimens from 80 ovarian carcinomas, using the anti-nm23, p53, and c-erbB-2 monoclonal antibodies. Immunohistochemical results were scored semiquantitatively. All patients were staged according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO) staging system (I-IV). Carcinomas were graded as low- or high-grade, according to the modified grading system recommended by Shimatzu and Silverberg. For univariate analysis, survival time was analyzed by Kaplan-Meier method, and the log-rank test was used to assess the differences between the groups. For multivariate analysis, Cox proportional hazard regression model was used to examine several parameters simultaneously.


RESULTS
Univariate analysis showed that advanced clinical stage (p<0.001); positive staining for nm23 (p<0.001), p53 (p=0.021), and c-erbB-2 (p=0.003) protein; high histological grade (p<0.001); and vascular invasion (p=0.006) were associated with shorter overall survival. Multivariate analysis revealed only clinical stage as an independent prognostic parameter (p=0.014). Multivariate analysis for early-stage disease showed that only the presence of vascular invasion was significantly associated with shorter survival (p=0.008), whereas none of the parameters analyzed for the advanced-stage disease showed independent predictive value for prognosis.


CONCLUSIONS
The overexpression of p53, nm23, and c-erbB-2 proteins was associated with other parameters characteristic of aggressive tumors, such as advanced clinical stage, high grade, and/or presence of vascular invasion. However, this overexpression had no independent prognostic value either for overall survival or survival corrected by clinical stages.
Tomić
Snjezana
S
Department of Pathology, Split University Hospital Center and School of Medicine, Croatia. snjezana.tomic@st.hinet.hr
Ilić Forko
Jadranka
J
Babić
Damir
D
Sundov
Dinka
D
Kuret
Sendi
S
Andelinović
Simun
S
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002277:Carcinoma / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000032:analysis*; D015999:Multivariate Analysis; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology*; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014157:Transcription Factors / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C517938:NME1 protein, human