- Previous research suggests that the development and progression of bladder cancer may be sex hormone–related
- In this study of bladder cancer tissue specimens, aromatase was detected in both tumor epithelium and tumor stroma
- In tumor stroma, aromatase expression correlated with factors reflecting aggressive tumor behavior
- High aromatase expression in tumor stroma was associated with significantly worse overall survival
- Endocrine therapy may eventually prove to have a role in the treatment of bladder cancer
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It is known that males have a higher incidence of bladder cancer than females, but are at lower risk of disease recurrence, progression and mortality. These observations suggest that the hormonal axis influences bladder tumor development and progression.
One avenue of inquiry into this issue has been to study aromatase, an enzyme that is critical in the synthesis of estrogens. A recent study of patients with bladder cancer showed that aromatase expression positively correlated with pathologic stage and inversely correlated with cancer-specific survival.
To build on those findings, researchers led by Chin-Lee Wu, MD, PhD, associate pathologist at Massachusetts General Hospital, measured aromatase expression in bladder cancer specimens taken from a tumor bank at Mass General. In Cancer Biology & Therapy, they report direct evidence that aromatase is involved in bladder progression and may be a prognostic factor.
The research team used immunohistochemical staining to evaluate aromatase expression in 88 patients who underwent cystectomy for bladder cancer between 2002 and 2010. There were 68 (77%) males and 20 (23%) females with a median age of 71 years and median overall survival of 21 months.
Aromatase expression was classified as high or low and was evaluated separately in tumor epithelium and tumor stroma. High aromatase expression was present in the samples in the epithelium (38%) and stroma (74%).
In tumor epithelium, high aromatase expression was detected more frequently in males than in females, although the difference was of borderline statistical significance ( = .07). In tumor stroma, high aromatase was not associated with gender, but it was significantly associated with higher pT stage and the presence of lymph node metastasis, lymphovascular invasion or distant metastases.
Overall survival in patients with high aromatase expression in tumor epithelium did not differ significantly from that of patients with low expression—over the entire cohort or when stratified by gender. The research team speculates that aromatase expression in tumor epithelium might be a protective factor in genitourinary malignancies, especially in males.
Patients who had high aromatase expression in tumor stroma had significantly worse overall survival than those with low aromatase expression. On subgroup analysis, the difference was significant only in male patients. In multivariate regression analysis, aromatase expression in tumor stroma was not an independent prognostic indicator.
The researchers believe that an improved understanding of the role of aromatase in bladder cancer may lead to the use of aromatase expression as a predictive biomarker for disease progression. They also envision that, as in breast cancer, aromatase inhibitors may eventually have a role in the treatment of bladder cancer.
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