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
<p>Abstract</p> <p>Background</p> <p>Over-expression of <it>HER2 </it>in a subset of breast cancers (<it>HER2</it>+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-03-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/10/108 |
| _version_ | 1818834335786074112 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Tubbs Raymond |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Over-expression of <it>HER2 </it>in a subset of breast cancers (<it>HER2</it>+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of <it>HER2</it>+ 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.</p> <p>Methods</p> <p>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 <it>HER2</it>+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in <it>HER2</it>+ 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).</p> <p>Results</p> <p>TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 <it>HER2</it>+ 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 <it>HER2</it>+ 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.</p> <p>Conclusions</p> <p>Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in <it>HER2+ </it>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 <it>HER2 </it>targeted therapy.</p> |
| first_indexed | 2024-12-19T02:33:11Z |
| format | Article |
| id | doaj.art-6b7dfb14b91241e496011af04e4cd692 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-19T02:33:11Z |
| publishDate | 2010-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-6b7dfb14b91241e496011af04e4cd6922022-12-21T20:39:33ZengBMCBMC Cancer1471-24072010-03-0110110810.1186/1471-2407-10-108The 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 recurrenceTubbs RaymondYoder Brian JBudd GDim DanielKhoury ThaerKulkarni Swati AVardarajan RamyaJanarthanan Bagi RHicks David GSchreeder Marshall TEstopinal Noel CBeck Rodney AWang YanlingRing Brian ZSeitz Robert SRoss Douglas T<p>Abstract</p> <p>Background</p> <p>Over-expression of <it>HER2 </it>in a subset of breast cancers (<it>HER2</it>+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of <it>HER2</it>+ 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.</p> <p>Methods</p> <p>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 <it>HER2</it>+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in <it>HER2</it>+ 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).</p> <p>Results</p> <p>TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 <it>HER2</it>+ 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 <it>HER2</it>+ 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.</p> <p>Conclusions</p> <p>Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in <it>HER2+ </it>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 <it>HER2 </it>targeted therapy.</p>http://www.biomedcentral.com/1471-2407/10/108 |
| spellingShingle | 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 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 BMC Cancer |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://www.biomedcentral.com/1471-2407/10/108 |
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