The expression of TRMT2A, a novel cell cycle regulated protein, identifies a subset of breast cancer patients with HER2 over-expression that are at an increased risk of recurrence

BMC Cancer

Research Article

Brian Z Ring¹  Yanling Wang¹  Douglas T Ross¹  Rodney A Beck²  Robert S Seitz²  Noel C Estopinal³  Marshall T Schreeder³  Raymond Tubbs⁴  Brian J Yoder⁴  G Thomas Budd⁴  Thaer Khoury⁵  Daniel Dim⁵  David G Hicks⁵  Swati A Kulkarni⁵  Ramya Vardarajan⁵  Bagi R Janarthanan⁵ 

[1] Clarient Inc, Aliso Veijo, California, USA;Clarient Inc, Huntsville, Alabama, USA;Clearview Cancer Center, Huntsville, Alabama, USA;The Cleveland Clinic Foundation, Cleveland, Ohio, USA;University of Rochester, Rochester, New York, USA;

关键词: Breast Cancer;    Trastuzumab;    Tissue Array;    Rabbit Monoclonal Antibody;    Progesterone Receptor Expression;   

DOI  :  10.1186/1471-2407-10-108

 received in 2009-03-27, accepted in 2010-03-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundOver-expression of HER2 in a subset of breast cancers (HER2+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of HER2+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients.MethodsA single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in HER2+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in HER2+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI).ResultsTRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 HER2+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 HER2+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts.ConclusionsStudies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in HER2+ breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with HER2 targeted therapy.

【 授权许可】

Unknown   
© Hicks et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.