Diagnostic Implications of L1, p16, and Ki-67Proteins and HPV DNA in Low-grade CervicalIntraepithelial Neoplasia

Summary: 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 (Po0.05). In contrast, L1 expression was inversely
correlated with malignant transformation. Patients with CIN1 were divided into 4 groups:
L1???p16þ, L1þp16???, L1???p16???, and L1þp16þ, 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???p16þ 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/DNAþ was evident in 52%of CIN1 cases, and within the
L1???p16þ 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 highrisk
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. Key Words: Cervix???CIN1???HPV DNA???L1???p16.