17β-hydroxysteroid dehydrogenase type 1 improves survival in serous epithelial ovarian tumors

Abstract

The incidence of ovarian cancer has been epidemiologically related to female reproductive events and hormone replacement therapy after menopause. This highlights the importance of evaluating the role of sexual steroid hormones in ovarian cancer by the expression of enzymes related to steroid hormone biosynthesis in the tumor cells. This study was aimed to evaluate the presence of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase and estrogen receptor alpha (ERα) in the tumor cells and their association with the overall survival in 111 patients diagnosed with primary ovarian tumors. Positive immunoreactivity for 17β-HSD1 was observed in 74% of the tumors. In the same samples, aromatase and ERα revealed 66% and 47% positivity, respectively. No association was observed of 17β-HSD1 expression with the histological subtypes and clinical stages of the tumor. The overall survival of patients was improved in 17β-HSD1-positive group in Kaplan-Meier analysis (P = 0.028), and 17β-HSD1 expression had a protective effect from multivariate proportional regression evaluation (HR = 0.44; 95% CI 0.24-0.9; P = 0.040). The improved survival was observed in serous epithelial tumors but not in nonserous ovarian tumors. The expression of 17β-HSD1 in the cells of the serous epithelial ovarian tumors was associated with an improved overall survival, whereas aromatase and ERα were not related to a better survival. The evaluation of hazard risk factors demonstrated that age and clinical stage showed worse prognosis, and 17β-HSD1 expression displayed a protective effect with a better survival outcome in patients of epithelial ovarian tumors.

Keywords: 17β-hydroxysteroid dehydrogenase; aromatase; epithelial ovarian tumor; estrogen receptor; ovarian cancer; overall survival.

Figure 1

Immunohistochemistry for 17β-HSD1, aromatase, and ERα in (A–C) high-grade serous carcinoma, (D–F) endometrioid carcinoma, (G–I) mucinous carcinoma, and (J–L) serous borderline tumor. Photomicrographs were obtained from similar regions of triple-positive samples. 17β-HSD1 and aromatase reactivity are detected in the cytoplasm of epithelial cells, ERα is visualized in a nuclear location. Bars represent 50 µm.

Figure 2

Survival curves of patients with epithelial ovarian tumor after Kaplan–Meier analysis according to 17β-HSD1-, ERα-, and aromatase-positive and -negative expression. (A) Whole cohort (n = 111), 17β-HSD1 positive n = 83, negative n = 28; aromatase positive n = 72, negative n = 38; ERα positive n = 51, negative n = 59. (B) Serous epithelial ovarian tumors (n = 62), 17β-HSD1 positive n = 45, negative n = 16; aromatase positive n = 39, negative n = 22; ERα positive n = 30, negative n = 31. (C) Nonserous ovarian tumors (n = 49), 17β-HSD1 positive n = 37, negative n = 12; aromatase positive n = 33, negative n = 16; ERα positive n = 21, negative n = 28. P-values were obtained from log-rank test.

Figure 3

Survival curves for 17β-HSD1 in the whole cohort of epithelial ovarian cancer stratified according to aromatase and ERα expression. (A) Aromatase-positive tumors n = 72, 17β-HSD1-positive arm n = 54, negative arm n = 18; aromatase-negative tumors, n = 38 17β-HSD1-positive arm n = 28, negative arm n = 10; (B) ERα-positive tumors n = , 17β-HSD1 positive arm n = , negative arm n = ; ERα-negative tumors n = 59, 17β-HSD1-positive arm n = 41, negative arm n = 18. P-values were obtained from log-rank test.