BMC Cancer (Mar 2010)

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

  • Tubbs Raymond,
  • Yoder Brian J,
  • Budd G,
  • Dim Daniel,
  • Khoury Thaer,
  • Kulkarni Swati A,
  • Vardarajan Ramya,
  • Janarthanan Bagi R,
  • Hicks David G,
  • Schreeder Marshall T,
  • Estopinal Noel C,
  • Beck Rodney A,
  • Wang Yanling,
  • Ring Brian Z,
  • Seitz Robert S,
  • Ross Douglas T

DOI
https://doi.org/10.1186/1471-2407-10-108
Journal volume & issue
Vol. 10, no. 1
p. 108

Abstract

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Abstract Background Over-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. Methods A 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). Results TRMT2A 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 HER2+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p Conclusions Studies 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.