Down-regulated nucleoside diphosphate kinase nm23-H1 expression is unrelated to high-risk human papillomavirus but associated with progression of cervical intraepithelial neoplasia and unfavourable prognosis in cervical cancer.
J Clin Pathol
; 59(10): 1044-51, 2006 Oct.
Article
in En
| MEDLINE
| ID: mdl-16537673
OBJECTIVE: One of the factors leading to an invasive phenotype is the nm23 family of metastases-associated genes. Of the six known members, nm23-H1 is the most frequently studied potential anti-metastatic gene in cervical cancer. However, the possible molecular links to oncogenic human papillomavirus (HPV) are completely unexplored as yet. MATERIALS AND METHODS: As a part of the HPV-Pathogen Istituto Superiore di Sanità study, a series of 150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions were examined by immunohistochemical staining for nm23-H1, and tested for HPV by polymerase chain reaction (PCR) with three sets of primers (MY09/11, GP5(+)/GP6(+) and short PCR fragment). Follow-up data were available on all patients with SCC, and 67 CIN lesions were monitored by serial PCR for clearance or persistence of HPV after cone treatment. RESULTS: A linear decrease (p = 0.001) was observed in nm23-H1 expression, starting from CIN1 (85% with normal expression), with the most dramatic down regulation on transition from CIN2 (70% normal) to CIN3 (39%) and further to SCC (25%). Reduced expression was associated with CIN3 or cancer at an odds ratio 8.72 (95% confidence interval 4.13 to 18.41). Nm23-H1 was of no use as a marker of the high-risk human papillomavirus (HR-HPV) type, and it did not predict clearance or persistence of HR-HPV after treatment of CIN. Importantly, nm23-H1 expression was a significant prognostic factor in cervical cancer, reduced expression being associated with lower survival (p = 0.022) in univariate analysis. In the multivariate (Cox) regression model, however, only the International Federation of Gynecology and Obstetrics stage (p = 0.001) and age (p = 0.011) remained independent prognostic predictors. CONCLUSIONS: Down-regulated nm23-H1 expression is markedly associated with progression from CIN2 to CIN3, and predicts poor prognosis in cervical cancer. Nm23-H1 down regulation is probably orchestrated by mechanisms independent of HR-HPV oncoproteins and is possibly related to the emergence of a proteolytic phenotype.
Full text:
1
Database:
MEDLINE
Main subject:
Papillomaviridae
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Uterine Cervical Dysplasia
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Uterine Cervical Neoplasms
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Nucleoside-Diphosphate Kinase
/
Papillomavirus Infections
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
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Adult
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Aged
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Aged80
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Female
/
Humans
/
Middle aged
Language:
En
Journal:
J Clin Pathol
Year:
2006
Type:
Article
Affiliation country:
Italy