Diagnostic implications of L1, p16, and Ki-67 proteins and HPV DNA in low-grade cervical intraepithelial neoplasia

Int J Gynecol Pathol. 2011 Nov;30(6):597-604. doi: 10.1097/PGP.0b013e31821ac4fd.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • Capsid Proteins* / biosynthesis
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Cell Transformation, Neoplastic / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Ki-67 Antigen / biosynthesis*
  • Neoplasm Proteins* / biosynthesis
  • Oncogene Proteins, Viral* / biosynthesis
  • Papillomaviridae
  • Papillomavirus Infections / complications
  • Polymerase Chain Reaction
  • Prognosis
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Capsid Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • HPV L1 protein, Human papillomavirus
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Oncogene Proteins, Viral