Differential Expression of Androgen Receptor in Type I and Type II Endometrial Carcinomas: A Clinicopathological Analysis and Correlation with Outcome

Abstract

Objectives: Endometrial carcinomas (EC) are the most common gynecological malignancies and are conventionally divided into type I and type II due to diagnostic and prognostic considerations. Female hormone expression in EC is extensively studied; however, data about androgen receptor (AR) expression in EC are sparse. We aimed to study AR expression in different types of EC at our institute and whether it had an impact on patient outcomes.

Methods: A retrospective analysis of EC cases diagnosed and treated from 2010-2019. AR immunohistochemical expression was tested in 52 EC cases (type I = 40; type II = 12). Histological typing was verified according to conventional diagnostic criteria. Only primary EC were included without neoadjuvant therapy. Histologic score was calculated as: stain intensity (graded 0-3) × positive cells percentage (graded 0-4). Level of expression was scored from 0 to 12.

Results: The mean age of the selected patients was 60.3 years (range = 31-88 ± 12.6). Recurrence was detected in 11 (21.2%) patients. The outcome was 40 patients were alive without disease, eight alive with disease, three dead of disease, and one dead of other causes. About 62.5% of type I-EC and 25.0% of type II-EC were AR positive. AR expression was analyzed against different clinicopathological parameters including: type (p = 0.005), histotype (p = 0.044); grade (p = 0.035); age group (p = 0.207); menopause (p = 0.086); estrogen receptor (ER) expression (p = 0.284); atypical complex hyperplasia (p = 0.594); tumor stage (p = 0.994); tumor recurrence (p = 0.530); node status (p = 0.110); and outcome (p = 0.202).

Conclusion: AR expression was higher in type I EC, endometrial endometrioid carcinoma histotype, and with a lower grade. AR expression was not significantly correlated with age, stage, ER, atypical hyperplasia, recurrence, node status, or outcome. Results agree with recent literature that AR expression is associated with better-differentiated EC and may be a potential hormonal therapeutic tool.

Keywords: Adenocarcinoma, Clear Cell; Androgen Receptor; Carcinoma, Endometrioid; Cystadenocarcinoma, Serous; Endometrial Cancer.

Figure 1

AR expression patterns in different types of endometrial cancer. Upper panel representative cases: (a) EEC: endometrial endometrioid carcinoma; (b) ECCC: endometrial clear cell carcinoma; (c), (d) Endometrial serous carcinoma (ESC) 1 and 2: two different cases of endometrial serous carcinoma (hematoxylin and eosin stain, magnification = 100 ×). (e-h) Lower panel displays corresponding AR expression by immunohistochemical stain, positivity indicated by the brown color (anti-AR, magnification = 100 ×).

Figure 2

Relationship between androgen receptor (AR) expression and level of expression with endometrial cancer (EC) grade.

Figure 3

Relationship between androgen receptor (AR) expression and histologic score with the type of endometrial carcinomas (EC).