Analysis and clinical implications of p53 gene mutations and human papillomavirus type 16 and 18 infection in primary adenocarcinoma of the uterine cervix.
Mutant p53 is frequently detected in endometrial and ovarian carcinoma, but it is rare in cervical cancers. Previous reports focused on cervical squamous cell carcinoma, whereas cervical adenocarcinoma was given little attention. We searched for p53 gene mutations in 74 primary cervical adenocarcinomas with known human papillomavirus (HPV) status. Our aim was to evaluate the prevalence of p53 mutations and to investigate their possible role as an independent prognostic factor. We found mutations in 13.5% with a high rate of G:C --> A:T transitions as observed in endometrial adenocarcinoma. As p53 mutations are more frequently detected in malignancies of high grade, high stage, and large size, this molecular event seems to play a role in the progression rather than in the induction of cervical adenocarcinoma. In our series, patients with HPV-negative tumors and patients with mutated neoplasms, irrespective of HPV infection, had a shorter survival. Yet the absence of HPV infection and presence of p53 mutations are not independent risk factors for tumor-related death after adjustment for clinicopathological confounders. The only significant and independent predictors of survival are age of patient, stage of disease, tumor grade, and presence of lymph node metastases.
Tenti
P
P
Department of Human Pathology, University of Pavia and Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Italy. tentiap@ipv36.unipv.it
Pavanello
S
S
Padovan
L
L
Spinillo
A
A
Vesentini
N
N
Zappatore
R
R
Migliora
P
P
Zara
C
C
Ranzani
G N
GN
Carnevali
L
L
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016158:Genes, p53; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics / Q000401:mortality / Q000821:virology; D011379:Prognosis; D016019:Survival Analysis; D014412:Tumor Virus Infections / Q000235:genetics / Q000401:mortality / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000821:virology*
D004279:DNA, Viral