P53, Bcl-2, PCNA expression and apoptotic rates during cervical tumorigenesis

Abstract

5068 Background: In order to estimate the apoptotic rates during the development of cervical cancer, we investigated apoptosis by morphological criteria and by the TUNEL assay, as well as by the expression of proteins related to this process such as p53, Bcl-2 and PCNA in lesions of all phases of tumor progression in the cervical epithelium. Methods: The expression of p53, Bcl-2 and PCNA proteins were immunohistochemically examined using 31 normal cervical epithelium, 10 low grade squamous lesions (CIN I), 28 high grade squamous lesions (CIN II/III) and 36 invasive squamous cell carcinomas (ISCC). The same samples were used for TUNEL assays and HPV detection by polymerase chain reaction (PCR) and sequence. Results:Human papillomavirus (HPV) presence is necessary but not sufficient for cervical cancer development, suggesting that cellular genes participate in tumor progression. PCNA protein expression was significantly increased as the grade of cervical lesion becomes higher from normal epithelium to ISCC. Surprisingly, p53 levels also increased with lesion degree. Apoptosis as determined by TUNEL assay, and PCNA protein expression show a significant positive correlation with increasing histological abnormality. Statistical analysis showed a positive correlation between p53 and PCNA expression in CIN I (r=0.378, P=0.016). A similar correlation was found between p53 and Bcl-2 expression in CIN II/III (r=0.385, P=0.023). A total of 76 of 105 (71.4%) cervical samples were HPV positive, with HPV 16 being the most common high-risk type detected (72.4%). Conclusions:Our results suggest that p53 protein overexpression during cervical tumorigenesis could be playing a pivotal role in cervical tumor progression as a late event. Although a stronger p53 than Bcl-2 expression in CIN II/III was detected, the up-regulation of Bcl-2 in ISCC suggests that protection against apoptosis is important for maintaining cervical neoplasia. PCNA protein expression increase may be a useful marker for diagnosis of various dysplasia grades and cervical cancer. No significant financial relationships to disclose.