Detection of estrogen receptor α and β in a relevant model of human invasive urinary bladder cancer.

Abstract

e15160 Background: Each year in the US, >14,000 people die from invasive urinary bladder cancer (transitional cell carcinoma, InvTCC). Defining effective means to prevent InvTCC development and growth is crucial. Estrogen receptors (ERs) are present in InvTCC, but their role in InvTCC progression and potential value as targets for intervention are not clearly defined. Naturally occurring canine InvTCC closely mimics human InvTCC in molecular features and biological behavior. Gender and neuter status affect InvTCC risk in dogs. Canine InvTCC may offer a relevant in vivo system to study the role of ERs. ERα and β expression in canine InvTCC, with comparison to human InvTCC, were studied as an initial step to determine the role of ERs in InvTCC. Methods: ERα and β expression were determined by immunohistochemistry in canine and human InvTCC samples and normal bladder tissues. The majority of tissues were obtained from patients that had received previous treatment. Antibodies for ERα (SC-7207) and ERβ (SC-8974) were obtained from Santa Cruz Biotechnology, Santa Cruz, CA. The percentages of immunoreactive tumor cells and staining intensity in 10 HPFs were recorded by 2 independent reviewers. Tissues with immunoreactivity in greater than 10% of tumor cells were considered positive for ER expression. Results: Results of immunohistochemistry are outlined in the table. Paired tissues from primary and metastatic InvTCC in 17 dogs were evaluated. The ER expression between sites correlated in 17 of 17 cases for ERα, and in 12 of 17 cases for ERβ. ERα and β expression was similar between tissues from males and females analyzed to date. Conclusions: ERα and β were expressed in canine InvTCC, similar to that in human InvTCC. Canine InvTCC offers a relevant system to define the role of ERs in InvTCC development and progression. ERα immunostaining ERβ immunostaining Canine InvTCC 34/39 (87%) 29/39 (74%) Human InvTCC 7/15 (47%) 11/15 (73%) Canine lung metastases 12/14 (86%) 8/14 (57%) Canine lymph node metastases 9/11 (82%) 9/11 (82%) Canine normal bladder 7/7 (100%) 4/6 (67%) Human normal bladder 12/14 (86%) 9/14 (64%)