Association of Aromatase With Bladder Cancer Stage and Long-Term Survival: New Insights Into the Hormonal Paradigm in Bladder Cancer

Nguyen, Daniel P.; O’Malley, Padraic; Furrer, Marc-Alain; Mongan, Nigel P.; Robinson, Brian D.; Wang, Gerald; Scherr, Douglas S.

doi:10.1016/j.clgc.2016.05.017

Cited by 13 publications

(22 citation statements)

References 26 publications

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“…This finding is consisted with the description of TE expression pattern in previous aromatase study in BCa. 21 There was no significant association of TE staining with pT stage or pN stage in our study. In addition, we did not find a significant association of high aromatase expression in TE with overall survival.…”

Section: Discussioncontrasting

confidence: 64%

“…10 Moreover, several studies have shown that expression of aromatase is correlated with tumorigenesis and/or progression in gender-related tumor types including breast cancer, 14 endometrial cancer, 15 cervical cancer, 16 ovarian cancer, 17 prostate cancer, 18 as well as tumors which may be sex hormone-related types including lung cancer, 19 colon cancer 20 and BCa. 21 The prognostic role of aromatase expression in TE has been discussed in breast cancer, endometrial cancer, lung cancer, BCa and prostate cancer, however this remains controversial. 18,[21][22][23][24] In addition, studies also highlighted the predictive and prognostic importance of intratumoral aromatase expression in TS in breast cancer, endometrial cancer and prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

“…21 The prognostic role of aromatase expression in TE has been discussed in breast cancer, endometrial cancer, lung cancer, BCa and prostate cancer, however this remains controversial. 18,[21][22][23][24] In addition, studies also highlighted the predictive and prognostic importance of intratumoral aromatase expression in TS in breast cancer, endometrial cancer and prostate cancer. 18,22,25 Aromatase inhibitor (AI), which can abolish tumor estrogen production and enhance androgenic activity, is customarily used as firstline treatment for advanced breast cancer.…”

Section: Introductionmentioning

confidence: 99%

“…26 A recent study revealed that aromatase expression in TE was positively correlated with pathologic stage and inversely correlated with cancer-specific survival in a cohort of BCa patients. 21 However, limited knowledge of aromatase activity in BCa was understood. In the present study, we aimed to examine the expression pattern of aromatase in BCa tissues, and to investigate its clinical significance in BCa malignancy.…”

Section: Introductionmentioning

confidence: 99%

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Expression of aromatase in tumor related stroma is associated with human bladder cancer progression

Wang

et al. 2018

Cancer Biology & Therapy

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Putative gender differences in bladder cancer (BCa) have been proposed to result from sex hormone influence. Aromatase is the key enzyme catalyzing the conversion of androgens to estrogens which may result in an intratumoral microenviroment with increased estrogen production. In this study, we investigated the expression pattern of aromatase and its association with BCa progression. Tissue samples from 88 BCa patients who underwent cystectomy were obtained. Using immunohistochemistry (IHC), expression of aromatase in tumor epithelium (TE) and tumor related stroma (TS) were evaluated separately, and the association of aromatase expression status with pathologic variables and overall survival (OS) outcome was examined. High aromatase expression was found in 33/88 (37.5%) of TE and in 65/88 (73.9%) of TS. Increased aromatase expression in TE had a trend to correlate with male gender. Increased aromatase in TS was significantly associated with adverse pathologic variables including higher pathologic pT, positive lymph node metastasis (pN), lymphovascular invasion (LVI), and distant metastasis. In univariate analysis, high aromatase expression in TS was significantly associated with poorer overall survival (p = 0.014), but this association was not significant (p = 0.163) in multivariate cox analysis adjusted for independent factors including age at surgery and pN. These results demonstrate that aromatase expression in TS but not TE may play a critical role in BCa progression. Our findings provide direct evidence of aromatase involvement in BCa and suggest endocrine therapy may have a potential role in the treatment of BCa.

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Section: Discussioncontrasting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of aromatase in tumor related stroma is associated with human bladder cancer progression

Wang

et al. 2018

Cancer Biology & Therapy

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“…SNPs located in the 3′-UTRs of genes may affect the expression of the gene by reinforcing, weakening or disrupting the miRNA-mRNA interaction, and thereby confer the individual's disease risk (21). Nguyen DP et al found that Aromatase expression was signi cantly associated with bladder cancer tumor stage, and Cox regression analysis demonstrated that aromatase expression was associated with a more than 2-fold risk of cancer recurrence (HR = 2.37) (13). After this, Shulin Wu et al also found that in 88 bladder cancer cases examined, high aromatase expression was present in 37.5% and 73.9% of Tumor epithelium (TE) and tumor related stroma (TS) respectively, and high aromatase expression in TS was signi cantly associated with poorer overall survival (22).…”

Section: Discussionmentioning

confidence: 99%

The correlation between Aromatase (CYP19A1) and Bladder cancer in Chinese Han Population

Zhang

Wen

et al. 2020

Preprint

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BackgroundSeveral P450 metabolic enzymes genes have been discovered that affect the genetic susceptibility of bladder cancer. While, there is no report about CYP19A1 gene polymorphism on the susceptibility of bladder cancer. So, we performed a case–control study to investigate the association between polymorphisms in CYP19A1 gene and the susceptibility to bladder cancer in Chinese Han population.Materials:Five SNPs were selected and genotyped in 217 patients and 550 healthy controls. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression adjusted for age and gender.ResultsWe found that CYP19A1 rs4646 “A” allele and rs17601876 “GA” genotype added the risk of bladder cancer (rs4646: OR = 1.28, 95%CI: 1.01 - 1.62, p = 0.043; rs17601876: OR= 1.64, 95%CI: 1.17 – 2.29, p = 0.004 ), while with rs6493487 “G” and rs1062033 “G” allele in CYP19A1 gene reduced the risk of bladder cancer (rs6493487: OR = 0.68, 95%CI: 0.51 - 0.89, p = 0.005; rs1062033: OR = 0.36, 95%CI: 0.28 - 0.47, p = 9.09E-16). WHO grade stratified analysis shown that rs6493487 (OR =0.42, 95%CI: 0.23 – 0.76, p = 0.004) and rs17601876 (OR =0.44, 95%CI: 0.23 – 0.85, p = 0.015) reduced the risk of bladder cancer with WHO III-IV, when compared with the bladder cancer with WHO I-II. Age stratified analysis shown that rs4646 “A”, rs6493487 “G”, and rs1062033 “G” allele were associated with bladder cancer risk.ConclusionOur results suggested that the Aromatase CYP19A1 gene has potential roles in the genetic susceptibility to bladder cancer.

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The Importance of CYP19A1 in Estrogen Receptor-Positive Cholangiocarcinoma

et al. 2018

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Association of Aromatase With Bladder Cancer Stage and Long-Term Survival: New Insights Into the Hormonal Paradigm in Bladder Cancer

Cited by 13 publications

References 26 publications

Expression of aromatase in tumor related stroma is associated with human bladder cancer progression

Expression of aromatase in tumor related stroma is associated with human bladder cancer progression

The correlation between Aromatase (CYP19A1) and Bladder cancer in Chinese Han Population

The Importance of CYP19A1 in Estrogen Receptor-Positive Cholangiocarcinoma

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