Estrogen and progesterone receptors in human papilloma virus-related cervical neoplasia

Abstract

Estrogen (ER) and progesterone (PR) receptors in the normal uterine cervix, cervical intraepithelial neoplasia and invasive carcinoma were studied in consecutive samples from Hospital do Câncer, São Paulo, between 1996 and 1997. Tissue was collected by removing a fragment of the tumoral area using a 5-mm diameter biopsy punch, followed by removal of a macroscopically normal area as close as possible from the tumor. Histopathological confirmation was obtained for all specimens analyzed. A total of 24 normal tissues, 17 cases of cervical intraepithelial neoplasia and 7 of invasive carcinomas were studied. The ER/PR ratio was determined by immunohistochemistry using monoclonal antibodies specific for each receptor. Adjacent tissue slides were submitted to generic PCR for human papillomavirus (HPV) DNA detection followed by typing by dot blot hybridization. About half (45.8%) of the tumors were HPV DNA positive while 29.1% of the patients were also HPV positive in their respective normal tissue. ER was negative in the tumoral epithelium of 11 HPV-positive patients (P = 0.04).

Functional association of oestrogen receptors with HPV infection in cervical carcinogenesis

“…Zhai and coworkers (Zhai et al 2010) have also observed a loss of ERα expression during CC progression starting from CIN I and CIN II/III and continuing to invasive squamous cell carcinoma with 50, 15 and 3.7% ERα positivity, respectively. In normal cervical tissue, Zhai and coworkers have observed 77% of ERα positivity, which is in line with the pattern observed by Coelho and coworkers (Coelho et al 2004). Zhai and coworkers have also noted that there is no correlation between HPV status or HPV type with the loss of ER expression, which is contrary to Nonogaki and coworkers.…”

“…Masood and coworkers demonstrated ERα (30%) and PR (35%) positivity in adenocarcinoma specimens, and this positive expression status correlated with prolonged patient survival (Masood et al 1993). Contrary to the above statement, the loss of ERα expression was established as an early alteration during the progression of cervical dysplasia to invasive carcinoma (Nonogaki et al 1990, Konishi et al 1991, Coelho et al 2004, Zhai et al 2010, López-Romero et al 2013, Nikolaou et al 2014. The majority of the basal cells in normal cervical tissue stained positive for ERα, whereas the percentage of ERα expression was decreased in CIN and squamous cervical carcinoma to 31% and 11%, respectively (Nikolaou et al 2014).…”

“…In contrast, PR expression tends to increase alongside CC progression with 29% for CIN and 49% for CIN and squamous cervical carcinoma. Indeed, Coelho and coworkers (Coelho et al 2004) observed around 21% of cervical tumour biopsies to be ERα positive in the tumour epithelium. However, around 50% ERα positivity was observed in the epithelium of the adjacent normal cervical tissue.…”

“…Alternatively, PR expression was not detected in either a normal or tumour epithelium of any case studied. Coelho and coworkers concluded that the propensity of ERα distribution in normal tissue to be opposite that of lesions and underlined the importance of viral factors that affect the expression patterns of steroid receptors (Coelho et al 2004). In a study, 93.7% ERα expression was detected in the epithelium of normal cervical tissues but not in invasive cervical carcinomas (0%) (López-Romero et al 2013).…”

“…ERα is expressed in the normal cervical epithelium and expression continues to decline during the various phases of CC progression (Nonogaki et al 1990, Konishi et al 1991, Coelho et al 2004, Zhai et al 2010, López-Romero et al 2013, Nikolaou et al 2014. In contrast to this trend, stromal ERα is expressed in both normal and cervical tumour tissues (Mosny et al 1989, Nonogaki et al 1990, Coelho et al 2004, López-Romero et al 2013).…”