Immunohistochemical detection of p53 in cervical epithelial lesions with or without infection of human papillomavirus types 16 and 18.
Using formalin-fixed and paraffin-embedded cervical tissues, we examined infection with human papillomavirus (HPV) types 16 and 18 by Southern blot analysis following polymerase chain reaction (PCR), and the accumulation of p53 protein by immunohistochemistry in 30 cases of normal or metaplastic cervix, 17 cases of cervical intraepithelial neoplasia grade I (CIN I), 20 cases of CIN II, 37 cases of CIN III and 23 cases of invasive squamous cell carcinoma (ISCC). In addition, we examined the ratio of HPV-infected cells by in situ hybridization (ISH) and the alteration of p53 gene using PCR followed by single-strand conformation polymorphism (PCR-SSCP) in 2 cases of CIN III and 12 cases of ISCC, in which overexpression of p53 was immunohistochemically detected. HPV DNA was detected in 5 cases (16.7%) of normal or metaplastic cervix, 5 cases (29.4%) of CIN I, 9 cases (45.0%) of CIN II, 26 cases (70.3%) of CIN III and 15 cases (65.2%) of ISCC. Positivity for HPV in the groups of CIN III and ISCC was significantly higher than in the normal or metaplastic cervix (P < 0.05). The accumulation of p53 was not detected in the normal or metaplastic cervix, CIN I and CIN II. High-level p53 accumulation was identified in basal and suprabasal atypical cells in 27.0% (10/37) of CIN III and in carcinoma cells in 43.5% (10/23) of ISCC cases, and low-level accumulation was identified in atypical cells of 35.1% (13/37) of CIN III and in carcinoma cells in 30.4% (7/23) of ISCC cases. The accumulation of p53 was found to coexist with infection by HPV in 17 (46.0%) of 37 CIN III cases and 12 (52.2%) of 23 ISCC cases, and high-level p53 accumulation was more frequently detected in HPV-positive ISCC cases. Either HPV infection or accumulation of p53 was found in 16.7% (5/30) of the cases of normal or metaplastic cervix, 29.4% (5/17) of CIN I, 45.0% (9/20) of CIN II, 86.5% (32/37) of CIN III and 87.0% (20/23) of ISCC cases. These results suggest that the inactivation of p53 function by HPV infection or alteration of p53 protein itself precedes the development of tumours with a fully malignant and invasive phenotype and plays an important role in tumorigenesis in the uterine cervix. ISH study provided no correlation between the degree of immunohistochemical positivity for p53 and the ratio of HPV-positive cells in the same lesions.(ABSTRACT TRUNCATED AT 400 WORDS)
Akasofu
M
M
Department of Pathology, School of Medicine, Kanazawa University, Ishikawa, Japan.
Oda
Y
Y
D001483:Base Sequence; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002584:Cervix Uteri / Q000737:chemistry; D005260:Female; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008679:Metaplasia / Q000235:genetics; D008969:Molecular Sequence Data; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014412:Tumor Virus Infections / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000821:virology*
D016159:Tumor Suppressor Protein p53