title: Diagnostic implications of L1, p16, and Ki-67 proteins and HPV DNA in low-grade cervical intraepithelial neoplasia.
abstract: 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<0.05). In contrast, L1 expression was inversely correlated with malignant transformation. Patients with CIN1 were divided into 4 groups: L1p16, L1p16, L1p16, and L1p16, 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 L1p16 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 L1p16 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.
authors: Second Department of Pathology, School of Medicine, University of Brescia, Spedali Civili 1, Brescia, Italy. l.benerini@virgilio.it
authors: Luisa Benerini
authors: LB
authors: Gatta
authors: Angiola
authors: A
authors: Berenzi
authors: Piera
authors: P
authors: Balzarini
authors: Enrico
authors: E
authors: Dessy
authors: Francesca
authors: F
authors: Angiero
authors: Giulio
authors: G
authors: Alessandri
authors: Angela
authors: A
authors: Gambino
authors: Piergiovanni
authors: P
authors: Grigolato
authors: Anna
authors: A
authors: Benetti
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D036022:Capsid Proteins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000473:pathology / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D036022:Capsid Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; C114580:HPV L1 protein, Human papillomavirus; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral