Publications (2)8.86 Total impact
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Article: Genetic heterogeneity of HER2 in breast cancer: impact on HER2 testing and its clinicopathologic significance.
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ABSTRACT: In 2009, ASCO/CAP expanded its human epidermal growth factor receptor type 2 (HER2) testing guideline to define HER2 genetic heterogeneity (GH). However, the clinical significance of GH is unclear. We investigated the impact of HER2 GH on HER2 testing and studied its clinicopathologic significance. Paraffin-embedded tumor tissues of surgical resections of 617 non-consecutive breast carcinoma patients were studied by routine HER2 fluorescence in situ hybridization (FISH). HER2 GH was evaluated, and the results were correlated with HER2 protein expression by immunohistochemistry and HER2 gene amplification by FISH, and with various clinicopathologic parameters. HER2 GH was observed in 15.2 % (94/617) of the patients. It was associated with low-to-middle level of HER2 expression, and with none-to-low level of HER2 gene amplification. Among the 17 patients with equivocal HER2 FISH results, 35.3 % (6/17) of tumors displayed GH. In contrast with HER2-positive tumors without GH, tumors with HER2 GH demonstrated significant association with lower histologic grade, smaller tumor size, and proclivity to hormone receptor expression. HER2 GH is a substantial cause of equivocal HER2 testing results of breast cancer by FISH. Tumors with HER2 GH showed that biologic features resemble more of HER2-negative tumors than HER2-positive tumors without GH. The findings indicate a need of the guidelines to clarify whether tumors with HER2 GH truly benefit from HER2-targeted therapy of breast cancer.Breast Cancer Research and Treatment 04/2012; 134(3):1095-102. · 4.43 Impact Factor -
Article: CD8⁺ cytotoxic T cell and FOXP3⁺ regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes.
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ABSTRACT: The prognostic significance of tumor-associated FOXP3(+) regulatory T cells (Tregs) and CD8(+) cytotoxic T lymphocytes (CTLs) in invasive breast carcinomas is studied. Tregs and CTLs were assessed by immunohistochemistry in 1270 cases of invasive breast carcinoma for their associations with patient survival, histopathologic features, and molecular subtypes. Infiltrates of Tregs and CTLs were observed within tumor bed and in the tissue surrounding tumor. Within tumor bed, increased infiltration of Tregs and CTLs was significantly more common in those with unfavorable histologic features, including high histologic grade and negative ER and PR status. In addition, high density Treg infiltration was also associated with tumor HER2 overexpression, decreased overall survival (OS) and progression-free survival (PFS). In tissue surrounding tumor, in contrast, high CTL/Treg ratio was found to be significantly associated with improved OS and PFS. These prognostic associations were confirmed by multivariate analysis. Furthermore, the density of Treg infiltrates within tumors was inversely correlated with the prognosis of the molecular subtypes of tumors. The ratio of CTL/Treg infiltrates in the surrounding tissue was also significantly higher in luminal than non-luminal subtypes of carcinoma. The prognostic significances of Tregs and CTLs in breast carcinoma depend on their relative density and location. The density of intratumoral Treg infiltrates and the peritumoral CTL/Treg ratio are independent prognostic factors and correlated with the prognosis of the molecular subtypes of breast carcinoma, which may serve as potential target for stratifying immunotherapy to battle against the aggressive subtypes of breast carcinoma.Breast Cancer Research and Treatment 06/2011; 130(2):645-55. · 4.43 Impact Factor
