Comparative evaluation of nm23 and p16 expression as biomarkers of high-risk human papillomavirus infection and cervical intraepithelial neoplasia 2(+) lesions of the uterine cervix.
OBJECTIVE
To investigate the clinical role of nm23 expression in identifying both high-risk human papillomavirus (HR-HPV) and high-grade cervical lesions or carcinomas [cervical intraepithelial neoplasia 2(+) (CIN2(+) )], and to compare it with p16 overexpression, as this latter biomarker has already been reported widely in HR-HPV infected cervical lesions.


RESULTS
Immunohistochemical evaluation of nm23 and p16 in 143 cervical biopsy specimens including negative, low- and high-grade lesions and squamous carcinomas (SC). HR-HPV testing by Digene hybrid capture 2 (HC2) and polymerase chain reaction (PCR) on the cervico-vaginal samples of the same patients. In detecting CIN2(+) , p16 was significantly more sensitive and specific than nm23 (96.3% versus 81.8% and 66% versus 36.4%, respectively, both P < 0.0001). Concerning HR-HPV detection by HC2, p16 showed a significantly higher specificity than nm23 (82% versus 47%, P <0.0001), although the sensitivities were comparable (71% versus 76%). We found a significantly direct correlation between nm23 and HC2 findings. However, nm23 expression did not correlate with HPV16/18 infection. In contrast, we observed a significant association between p16 overexpression and HPV16/18 genotypes.


CONCLUSIONS
We confirm the diagnostic value of p16 overexpression. Moreover, despite in vitro data regarding the interaction with the HPV-E7 protein, nm23 does not appear to be a more useful biomarker than p16 in identifying CIN2(+) or HR-HPV infection.
Benevolo
Maria
M
Departments of Pathology Epidemiology Scientific Direction Oncologic Gynecology, Regina Elena Cancer Institute, Rome, Italy. benevolo@ifo.it
Terrenato
Irene
I
Mottolese
Marcella
M
Marandino
Ferdinando
F
Muti
Paola
P
Carosi
Mariantonia
M
Rollo
Francesca
F
Ronchetti
Livia
L
Mariani
Luciano
L
Vocaturo
Giuseppe
G
Vocaturo
Amina
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases / Q000032:analysis* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000032:analysis* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000473:pathology* / Q000821:virology
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins; C517938:NME1 protein, human