title: Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix.
abstract: The prognostic effect of c-myc oncogene overexpression was assessed in a multivariate analysis of 93 patients with invasive carcinoma of the cervix, stage Ib, IIa, and IIb proximal. The treatment was based on the association of brachytherapy-colpohysterectomy and lymphadenectomy. Analysis of c-myc gene expression was done using Northern and slot blot hybridization techniques. Overexpression of c-myc (ie, levels at least three times the mean observed in normal tissues) was present in 33% of the tumors. The proportion of carcinomas with c-myc overexpression significantly increased with the size of the primary tumor (P = .04). No relationship was found between c-myc overexpression and the other clinical and histologic parameters, including the nodal status. The relative risk of relapse (overall, pelvic failure, distant metastases) was analyzed in a Cox's proportional hazards model. Three factors were significantly related to the risk of overall relapse when the multivariate analysis was performed, namely, the tumor size, the nodal status, and c-myc expression. A combination of c-myc expression and the nodal status provided a very accurate indication of the risk of relapse. Indeed, patients with negative nodes had a 3-year disease-free survival rate of 93% (95% confidence interval [Cl], 79% to 98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% Cl, 26% to 63%) when c-myc was overexpressed (log-rank test, P = .02). In addition, in the subgroup of patients with positive nodes, this rate was 44% (95% Cl, 25% to 77%) and 15% (95% Cl, 4% to 49%) when c-myc gene was expressed at normal level, or overexpressed, respectively. Finally, c-myc gene overexpression was, in the multivariate analysis, the first factor selected by the model regarding the risk of distant metastases.
authors.affiliation: Département de Statistiques, INSERM U 287, Institut Gustave Roussy, Villejuif, France.
authors.forename: J
authors.initials: J
authors.lastname: Bourhis
authors.forename: M G
authors.initials: MG
authors.lastname: Le
authors.forename: M
authors.initials: M
authors.lastname: Barrois
authors.forename: A
authors.initials: A
authors.lastname: Gerbaulet
authors.forename: D
authors.initials: D
authors.lastname: Jeannel
authors.forename: P
authors.initials: P
authors.lastname: Duvillard
authors.forename: V
authors.initials: V
authors.lastname: Le Doussal
authors.forename: D
authors.initials: D
authors.lastname: Chassagne
authors.forename: G
authors.initials: G
authors.lastname: Riou
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc