The possible role of bcl–2 expression in the progression of tumors of the uterine cervix

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Abstract
Background. A close link between human papillomavirus (HPV) and the development of uterine cervical neoplasias has been proposed. However, other cofactors also are required for malignant transformation. Methods. Forty‐six cervical intraepithelial neoplasias (CIN) I/II, 75 CIN III, and 60 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl‐2 protein (bcl‐2), bax protein (Bax), estrogen receptor (ER), and progesterone receptor (PR). The presence of HPV‐DNA was examined using the polymerase chain reaction assay. Results. bcl‐2 immunoreactivity was found in 17 of 46 (37%) CIN I/II, 48 of 75 (64%) CIN III, and 12 of 60 (20%) ISCC, the positivity in CIN III being significantly higher than in CIN I/II or ISCC (P < 0.004, P=0.0001). The bcl‐2 immunostaining pattern could be subdivided into two groups, basal type and diffuse type, with the incidence of the latter being clearly increased, in line with tumor progression. In the Bax or HPV‐DNA positive groups, bcl‐2 positive cases in CIN I/II were in the minority, whereas in CIN III they constituted the majority. In ISCC, bcl‐2 positive was significantly lower than negative cases, not being associated with Bax and HPV‐DNA. Estrogen receptor and PR immunoreactivity were rare. Conclusions. These results indicate that bcl‐2 may play an important role in a relatively early stage of cervical tumorigenesis, in association with Bax expression and HPV infection. Cancer 1995; 76:2297–303.