Abstract
The p16INK4a is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclin-dependent kinases involved in the phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7 oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16 pathway, leads to p16 upregulation. Although it is widely reported that p16 is overexpressed in a high percentage of preneoplastic lesions and in almost all carcinomas of the uterine cervix, protein upregulation and its correlation with HPV infection in low-grade lesions is still being debated. In this study, we investigated in parallel, p16 expression and HPV infection in 100 cervical biopsies (17 normal tissues, 54 CIN1, 10 CIN2, 11 CIN3, eight invasive squamous cancers). Results obtained demonstrated that none of the 17 normal cervical tissues, evaluated by immunohistochemistry, presented p16 positivity whereas, starting from CIN1 (31%) to CIN2 (90%), CIN3 (100%) and carcinomas (100%), a constant and significant increase of protein overexpression (P <0.0001) was observed. In addition, pi 6 overexpression consistently showed elevated sensitivity (84%) and specificity (98%) in detecting HR-HPV infection with a high positive predictive value (97%) and negative predictive value (86%). Of interest, 93% of the p16-positive CIN1 were also HR-HPV infected. Our findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and further demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade lesions.
| Original language | English |
|---|---|
| Pages (from-to) | 384-391 |
| Number of pages | 8 |
| Journal | Modern Pathology |
| Volume | 19 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2006 |
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Keywords
- Cervical intraepithelial neoplasia
- Human papillomavirus
- p16
- Progression risk
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Immunohistochemical expression of p16INK4a is predictive of HR-HPV infection in cervical low-grade lesions. / Benevolo, Maria; Mottolese, Marcella; Marandino, Ferdinando; Vocaturo, Giuseppe; Sindico, Roberto; Piperno, Giulia; Mariani, Luciano; Sperduti, Isabella; Canalini, Paola; Donnorso, Raffaele P.; Vocaturo, Amina.
In: Modern Pathology, Vol. 19, No. 3, 03.2006, p. 384-391.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunohistochemical expression of p16INK4a is predictive of HR-HPV infection in cervical low-grade lesions
AU - Benevolo, Maria
AU - Mottolese, Marcella
AU - Marandino, Ferdinando
AU - Vocaturo, Giuseppe
AU - Sindico, Roberto
AU - Piperno, Giulia
AU - Mariani, Luciano
AU - Sperduti, Isabella
AU - Canalini, Paola
AU - Donnorso, Raffaele P.
AU - Vocaturo, Amina
PY - 2006/3
Y1 - 2006/3
N2 - The p16INK4a is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclin-dependent kinases involved in the phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7 oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16 pathway, leads to p16 upregulation. Although it is widely reported that p16 is overexpressed in a high percentage of preneoplastic lesions and in almost all carcinomas of the uterine cervix, protein upregulation and its correlation with HPV infection in low-grade lesions is still being debated. In this study, we investigated in parallel, p16 expression and HPV infection in 100 cervical biopsies (17 normal tissues, 54 CIN1, 10 CIN2, 11 CIN3, eight invasive squamous cancers). Results obtained demonstrated that none of the 17 normal cervical tissues, evaluated by immunohistochemistry, presented p16 positivity whereas, starting from CIN1 (31%) to CIN2 (90%), CIN3 (100%) and carcinomas (100%), a constant and significant increase of protein overexpression (P <0.0001) was observed. In addition, pi 6 overexpression consistently showed elevated sensitivity (84%) and specificity (98%) in detecting HR-HPV infection with a high positive predictive value (97%) and negative predictive value (86%). Of interest, 93% of the p16-positive CIN1 were also HR-HPV infected. Our findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and further demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade lesions.
AB - The p16INK4a is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclin-dependent kinases involved in the phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7 oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16 pathway, leads to p16 upregulation. Although it is widely reported that p16 is overexpressed in a high percentage of preneoplastic lesions and in almost all carcinomas of the uterine cervix, protein upregulation and its correlation with HPV infection in low-grade lesions is still being debated. In this study, we investigated in parallel, p16 expression and HPV infection in 100 cervical biopsies (17 normal tissues, 54 CIN1, 10 CIN2, 11 CIN3, eight invasive squamous cancers). Results obtained demonstrated that none of the 17 normal cervical tissues, evaluated by immunohistochemistry, presented p16 positivity whereas, starting from CIN1 (31%) to CIN2 (90%), CIN3 (100%) and carcinomas (100%), a constant and significant increase of protein overexpression (P <0.0001) was observed. In addition, pi 6 overexpression consistently showed elevated sensitivity (84%) and specificity (98%) in detecting HR-HPV infection with a high positive predictive value (97%) and negative predictive value (86%). Of interest, 93% of the p16-positive CIN1 were also HR-HPV infected. Our findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and further demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade lesions.
KW - Cervical intraepithelial neoplasia
KW - Human papillomavirus
KW - p16
KW - Progression risk
UR - http://www.scopus.com/inward/record.url?scp=33244466951&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33244466951&partnerID=8YFLogxK
U2 - 10.1038/modpathol.3800551
DO - 10.1038/modpathol.3800551
M3 - Article
C2 - 16415792
AN - SCOPUS:33244466951
VL - 19
SP - 384
EP - 391
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 3
ER -