TY - JOUR
T1 - Diagnostic implications of L1, p16, and Ki-67 proteins and HPV DNA in low-grade cervical intraepithelial neoplasia
AU - Gatta, Luisa Benerini
AU - Berenzi, Angiola
AU - Balzarini, Piera
AU - Dessy, Enrico
AU - Angiero, Francesca
AU - Alessandri, Giulio
AU - Gambino, Angela
AU - Grigolato, Piergiovanni
AU - Benetti, Anna
PY - 2011/11
Y1 - 2011/11
N2 - The expressions of p16, Ki-67, and L1 proteins and human papillomavirus DNA were investigated using polymerase chain reaction (HPV/PCR) and catalyzed signal-amplified colorimetric DNA in situ hybridization (CSAC/ISH) as potential molecular markers for the diagnosis and transforming potential of low cervical intraepithelial neoplasia (CIN1). Ki-67 and p16 protein expression increased linearly from control cases to more dysplastic cases (CIN1, CIN2, and CIN3), peaking in squamous cell carcinoma cases (P-p16 +, L1 +p16 -, L1 -p16 -, and L1 +p16 +, and the immunohistochemical results were combined with HPV/PCR, L1/PCR, and high-risk E6/E7 genome and CSAC/ISH data. Malignant transformation correlated with L1 -p16 + patients (100% of CIN2, CIN3, and squamous cell carcinoma cases) and was evident in approximately 23% of CIN1 cases. In addition, the presence of HPV/DNA + was evident in 52% of CIN1 cases, and within the L1 -p16 + group. In 4 of 7 cases, the high-risk E6/E7 HPV genome was present and in 1 case it was integrated into the host DNA, as confirmed using CSAC/ISH. In patients with CIN1, investigating the presence of HPV/DNA using PCR and the presence of the high-risk E6/E7 genome is necessary to distinguish high-risk oncogenic patient groups from low-risk groups. This study highlights the importance of combining immunohistochemical analysis with HPV/PCR and CSAC/ISH to identify patients with CIN1 with a risk of neoplastic progression.
AB - The expressions of p16, Ki-67, and L1 proteins and human papillomavirus DNA were investigated using polymerase chain reaction (HPV/PCR) and catalyzed signal-amplified colorimetric DNA in situ hybridization (CSAC/ISH) as potential molecular markers for the diagnosis and transforming potential of low cervical intraepithelial neoplasia (CIN1). Ki-67 and p16 protein expression increased linearly from control cases to more dysplastic cases (CIN1, CIN2, and CIN3), peaking in squamous cell carcinoma cases (P-p16 +, L1 +p16 -, L1 -p16 -, and L1 +p16 +, and the immunohistochemical results were combined with HPV/PCR, L1/PCR, and high-risk E6/E7 genome and CSAC/ISH data. Malignant transformation correlated with L1 -p16 + patients (100% of CIN2, CIN3, and squamous cell carcinoma cases) and was evident in approximately 23% of CIN1 cases. In addition, the presence of HPV/DNA + was evident in 52% of CIN1 cases, and within the L1 -p16 + group. In 4 of 7 cases, the high-risk E6/E7 HPV genome was present and in 1 case it was integrated into the host DNA, as confirmed using CSAC/ISH. In patients with CIN1, investigating the presence of HPV/DNA using PCR and the presence of the high-risk E6/E7 genome is necessary to distinguish high-risk oncogenic patient groups from low-risk groups. This study highlights the importance of combining immunohistochemical analysis with HPV/PCR and CSAC/ISH to identify patients with CIN1 with a risk of neoplastic progression.
KW - Cervix
KW - CIN1
KW - HPV DNA
KW - L1
KW - p16
UR - http://www.scopus.com/inward/record.url?scp=80053975516&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053975516&partnerID=8YFLogxK
U2 - 10.1097/PGP.0b013e31821ac4fd
DO - 10.1097/PGP.0b013e31821ac4fd
M3 - Article
C2 - 21979598
AN - SCOPUS:80053975516
VL - 30
SP - 597
EP - 604
JO - International Journal of Gynecological Pathology
JF - International Journal of Gynecological Pathology
SN - 0277-1691
IS - 6
ER -