Down Regulation of Estrogen Receptor Expression is an Early Event in Human Papillomavirus Infected Cervical Dysplasia

Purpose: To study the alterations in hormonal sensitivity in relation to proliferative activity during the development of cervical dysplasia in women infected with high-risk human papillomavirus (hr-HPV).

Methods: Three to five biopsies of the cervix of eight patients were taken at colposcopy. Dysplasia was detected in 22 of the 32 biopsies, and 20 of these 22 biopsies contained hr-HPV. The labeling index (LI) as well as the intensity of staining of the MIB-1-, estrogen receptor (ER)-, and progesterone receptor (PR)-expression was assessed in each biopsy, including normal epithelium directly adjacent to the dysplastic lesions.

Results: Statistical analysis showed a significant increase in the MIB-1 LI with increasing severity of the dysplasia. The ER LI and ER intensity of staining in dysplastic lesions, as well as in morphologically normal epithelium directly adjacent to the dysplasia, showed a significant inverse relation with the severity of the dysplasia. The PR LI and intensity of staining did not differ between normal epithelium and dysplasia. The ER/MIB-1 ratio (including the ER LI and ER intensity of staining), and the PR/MIB-1 ratio (intensity of staining only) in dysplastic lesions showed a significant inverse relation with the severity of the dysplasia, while no alterations in these ratios were observed in morphologically normal epithelium adjacent to the dysplasia.

Conclusion: Down regulation of ER expression may be the first alteration to take place in normal epithelium during the development of cervical dysplasia in women infected with hr-HPV. The significant decrease in the ER/MIB-1-, and PR/MIB-1-ratio in progressively dysplastic lesions indicates a loss of normal growth control by sex steroid hormones, which is not observed in normal epithelium.