Bcl-2 predicts response to neoadjuvant chemotherapy and is overexpressed in lymph node metastases of urothelial cancer of the bladder

Kiss, Bernhard; Skuginna, Veronika; Fleischmann, Achim; Bell, Robert H; Collins, Colin; Thalmann, George; Seiler, Roland (2015). Bcl-2 predicts response to neoadjuvant chemotherapy and is overexpressed in lymph node metastases of urothelial cancer of the bladder. Urologic oncology - seminars and original investigations, 33(4), 166.e1-166.e8. Elsevier 10.1016/j.urolonc.2014.12.005

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PURPOSE To assess whether Bcl-2, an inhibitor of the apoptotic cascade, can predict response to neoadjuvant chemotherapy in patients with urothelial cancer of the bladder (UCB). METHODS Bcl-2 expression was analyzed in 2 different tissue microarrays (TMAs). One TMA was constructed of primary tumors and their corresponding lymph node (LN) metastases from 152 patients with chemotherapy-naive UCB treated by cystectomy and pelvic lymphadenectomy (chemotherapy-naive TMA cohort). The other TMA was constructed of tumor samples obtained from 55 patients with UCB before neoadjuvant chemotherapy (transurethral resection of the bladder cancer) and after cystectomy with pelvic lymphadenectomy (residual primary tumor [ypT+], n = 38); residual LN metastases [ypN+], n = 24) (prechemotherapy/postchemotherapy TMA cohort). Bcl-2 overexpression was defined as 10% or more cancer cells showing cytoplasmic immunoreactivity. RESULTS In both TMA cohorts, Bcl-2 overexpression was significantly (P<0.05) more frequent in LN metastases than in primary tumors (chemotherapy-naive TMA group: 18/148 [12%] in primary tumors vs. 39/143 [27%] in metastases; postchemotherapy TMA: ypT+7/35 [20%] vs. ypN+11/19 [58%]). In the neoadjuvant setting, patients with Bcl-2 overexpression in transurethral resection of the bladder cancer specimens showed significantly (P = 0.04) higher ypT stages and less regression in their cystectomy specimens than did the control group, and only one-eighth (13%) had complete tumor regression (ypT0 ypN0). In survival analyses, only histopathological parameters added significant prognostic information. CONCLUSIONS Bcl-2 overexpression in chemotherapy-naive primary bladder cancer is related to poor chemotherapy response and might help to select likely nonresponders.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Kiss, Bernhard; Skuginna, Veronika; Fleischmann, Achim; Thalmann, George and Seiler, Roland

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1078-1439

Publisher:

Elsevier

Language:

English

Submitter:

Katharina Morgenegg

Date Deposited:

26 Feb 2015 13:31

Last Modified:

05 Nov 2015 10:33

Publisher DOI:

10.1016/j.urolonc.2014.12.005

PubMed ID:

25596645

Uncontrolled Keywords:

Bladder cancer, Neoadjuvant chemotherapy, Response prediction, Bcl-2

BORIS DOI:

10.7892/boris.63400

URI:

https://boris.unibe.ch/id/eprint/63400

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