nm23-H1 expression defines a high-risk subpopulation of patients with early-stage epithelial ovarian carcinoma.
The role of the nm23 gene in human ovarian cancer is still controversial. We studied the expression of the nm23-H1 gene in 247 human epithelial ovarian carcinomas. The patients were followed-up until their death, or for a minimum of 5 years if they survived. The expression of the gene was studied by means of immunohistochemistry and a semiquantitative scoring system considering the staining intensity and the number of reactive tumour cells. Patients carrying tumours with higher expression scores (4-6 on a scale from 0 to 6) had a significantly lower survival (P = 0.01) than the rest. Further stratified statistical analysis revealed that this effect was mainly attributable to the subgroup of patients with early-stage (I and II), well- and moderately differentiated tumours. In fact, a multivariate analysis carried out for this subset of patients showed nm23-overexpression to be the only significant independent predictor of an ominous prognosis. The association of nm23-overexpression with a worse prognosis was most probably not due to mutation of the nm23 gene, since mutational analysis in 60 tumours by means of single-strand conformational polymorphism and direct sequencing disclosed only one mutation, which was located outside the open reading frame. Our results seem to indicate that nm23 expression is associated with a significantly worse prognosis in early-stage, well-differentiated epithelial ovarian carcinoma, a finding with important clinical implications, considering that many patients with ovarian cancers showing these features do not undergo any further treatment beyond surgical staging. If confirmed, they could help in tailoring the treatment of these patients in the future.
Schneider
J
J
Universidad del País Vasco, Departamento de Especialidades Médico-Quirúgicas, Bilbao, Spain.
Pollán
M
M
Jiménez
E
E
Marenbach
K
K
Martínez
N
N
Volm
M
M
Marx
D
D
Meden
H
H
D000368:Aged; D000704:Analysis of Variance; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins