Knockdown of long non-coding HOTAIR enhances the sensitivity to progesterone in endometrial cancer by epigenetic regulation of progesterone receptor isoform B

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in São Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The χ2 test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.

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An immunohistochemical study of estrogen and progesterone receptors in adenocarcinoma of the endometrium and in the adjacent mucosa

International Journal of Gynecological Cancer ◽

10.1046/j.1525-1438.1995.05040275.x ◽

1995 ◽

Vol 5 (4) ◽

pp. 275-281 ◽

Cited By ~ 6

Author(s):

H. Kerner ◽

E. Sabo ◽

M. Friedman ◽

D. Beck ◽

O. Samare ◽

...

Keyword(s):

Estrogen Receptor ◽

Endometrial Cancer ◽

Progesterone Receptor ◽

Estrogen Receptor Status ◽

Endometrial Adenocarcinoma ◽

Progesterone Receptors ◽

Myometrial Invasion ◽

Inverse Correlation ◽

Immunohistochemical Analysis ◽

Receptor Status

The immunoperoxidase stain for estrogen and progesterone receptor content in endometrial adenocarcinoma was correlated with the grade and stage, level of myometrial invasion, age and survival of the patients. Anti-estrogen and anti-progesteone receptor monoclonal antibodies were applied to paraffin-embedded tissue from hysterectomy specimens of 100 patients with adenocarcinoma of the endometrium. In 34 of the cases the receptors were studied in the endometrium adjacent to the tumor and compared to the nuclear receptor content in the carcinoma. There was a high inverse correlation between the estrogen receptor status and the grade of tumor (R= − 0.45,P= 0.006). The estrogen receptor measured in the endometrium near the tumor showed a negative correlation with the grade of the tumor (R= −0.42,P= 0.013). The estrogen, but not the progesterone, receptor content, was positively related to the age of the patient (P< 0.05). No significant correlation of the receptor status with the depth of myometrial invasion was found, despite the obvious interdependence between the grade and myometrial invasion. The progesterone receptor staining index appeared to be a distinct independent prognostic factor in endometrial cancer. The immunohistochemical analysis of the steroid hormone status in endometrial cancer therefore offers an alternative to the quantitative ligand-binding assay.

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