Immunocytochemical study of TOP2A and Ki-67 in cervical smears from women under routine gynecological care.

BACKGROUND

Cervical cancer is one of the most common female cancers and is caused by human papillomavirus (HPV). Viral infection leads to cell cycle deregulation by inactivating p53 and retinoblastoma protein by viral oncoproteins E6 and E7, respectively. Then, nuclear proteins such as DNA topoisomerase type IIa (TOP2A) and Ki-67 show increased expression because of increased cell division. These molecules are used as biomarkers for immunohistochemistry analysis of cervical tissue.

METHODS

In this cross-sectional study, we recruited 110 women receiving regular gynecological surveillance at public health centers in Olinda - PE, Brazil. Cervicovaginal cells were collected to determine the presence of cytological abnormalities and HPV infection. Pap smear slides were used to evaluate the expression of TOP2A and Ki-67 using immunocytochemistry techniques.

RESULTS

Of the 110 women, 75.4 % showed HPV-DNA(+) infection (83/110) and 29.1 % showed cellular abnormalities (32/110). Two atypical cells of undetermined significance, one low-grade squamous intraepithelial lesion, and one high-grade squamous intraepithelial lesion samples showed no HPV-DNA. TOP2A was positive in 71.9 % of samples, while Ki-67 was positive in 81.2 %. Immunocytochemistry results were positive in 4 of 5 atypical cells of undetermined significance samples. In HPV-DNA(+) samples with cytological abnormalities, immunocytochemistry results were positive 96.4 % of samples (p < 0.0001; odds ratio = 28.0). Among the samples infected with HR-HPV, TOP2A(+) was effective in 71 % samples, while and Ki-67(+) was 77.4 %. Ki-67 and TOP2A were positive for all samples infected with HPV6, HPV11, and HPV18. Ki-67 was also positive for all HPV16 samples, except for one negative sample in cytopathology analysis.

CONCLUSIONS

TOP2A and Ki-67 antibodies may be used in combination for cervical cancer screening in immunocytochemistry assays.