Universität zu Köln

Breyer, Johannes, Wirtz, Ralph Markus, Otto, Wolfgang, Laible, Mark, Schlombs, Kornelia, Erben, Philipp ORCID: 0000-0002-8279-7636, Kriegmair, Maximilian Christian, Stoehr, Robert, Eidt, Sebastian, Denzinger, Stefan, Burger, Maximilian and Hartmann, Arndt (2017). Predictive value of molecular subtyping in NMIBC by RT-qPCR of ERBB2, ESR1, PGR and MKI67 from formalin fixed TUR biopsies. Oncotarget, 8 (40). S. 67684 - 67696. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Expression of ESR1, PGR, HER2 and Ki67 is important for risk stratification and therapy in breast cancer. Hormone receptor expression can also be found in MIBC, reflecting luminal and basal subtypes of breast cancer. Thus the purpose was to investigate on the mRNA expression of the aforementioned markers and their prognostic value in pT1 bladder cancer. Retrospective analysis of clinical data and Formalin-Fixed Paraffin-Embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder was performed. mRNA expression was measured by single step RT-qPCR. Relative gene expression was determined by normalization to two housekeeping genes (CALM2, B2M) using the 40-Delta Delta CT method. Correlation of mRNA expression with outcome was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis. From overall 302 patients, 255 samples could be analyzed with valid measurements. Subtype distribution was Luminal-A in 11.4%, Luminal-B in 38.8%, triple negative in 36.9% and ERBB2 in 12.9%, respectively. Kaplan-Meier analysis revealed molecular subtyping being statistical significant for RFS (p=0.0408) and PFS (p=0.0039). Luminal-A patients did have the best RFS and PFS. Multivariate analysis revealed molecular subtyping to be significant for PFS (L-R Chi(2) of 11.89, p=0.0078). Elevated expression of HER2 was statistically significant for PFS (p=0.0025) and discriminated among G3 tumors a high risk group (60% PFS) from a low risk risk group (90% PFS) after 5 year follow-up (p<0.001). Expression of ESR1, PGR and HER2 has predictive value in stage pT1 NMIBC and reveals potential therapeutic targets.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Breyer, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Ralph Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Otto, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Laible, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlombs, Kornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Erben, Philipp UNSPECIFIED orcid.org/0000-0002-8279-7636 UNSPECIFIED Kriegmair, Maximilian Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoehr, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Eidt, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Denzinger, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Burger, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Arndt UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-217653
Journal or Publication Title:	Oncotarget
Volume:	8
Number:	40
Page Range:	S. 67684 - 67696
Date:	2017
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BACILLUS-CALMETTE-GUERIN; INVASIVE BLADDER-CANCER; BREAST-CANCER; UROTHELIAL CARCINOMA; RISK STRATIFICATION; LUMINAL SUBTYPES; PROGNOSTIC VALUE; STAGE; PROGRESSION; MARKERS Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21765