Abstract: We evaluated intratumoral heterogeneity of 30 ductal breast carcinomas with HER2/neu amplification, scored by the American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) criteria, and 3+ immunoexpression. High-grade (ratio > or =4.0) vs low-grade amplification (ratio >2.2 to <4.0) and chromosome 17 polysomy were also evaluated. On whole tissue sections, 20 tumors (67%) showed high-grade and 10 (33%) showed low-grade HER2/ neu amplification. Of 20 tumors with high-grade amplification, 14 (70%) showed no intratumoral genotypic heterogeneity; 6 (30%) showed at least 1 core with low-grade amplification. Of 10 cases with low-grade amplification, 6 (60%) showed no intratumoral heterogeneity; 4 (40%) showed chromosome 17 polysomy without gene amplification in 2 of 3 cores per case. Of 30 cases with gene amplification, 4 (13%) showed a "not-amplified pattern" in other parts of the tumor. The routine assessment of HER2/neu amplification using the ASCO/CAP criteria on whole tissue sections is not significantly confounded by intratumoral heterogeneity in breast cancer with high-grade amplification; however, genetic heterogeneity exists in a subset of breast carcinomas with low-grade amplification. The clinical relevance and impact on treatment outcome of intratumoral heterogeneity in breast cancer with low-grade HER2/neu amplification or chromosome 17 polysomy need further investigation.

Genotypic Intratumoral Heterogeneity in Breast Carcinoma with HER2/neu Amplification Evaluation According to ASCO/CAP Criteria

BRUNELLI, Matteo;MANFRIN, Erminia;MARTIGNONI, Guido;REMO, Andrea;REGHELLIN, Daniela;BERSANI, Samantha;GOBBO, Stefano;ECCHER, Albino;CHILOSI, Marco;BONETTI, Franco
2009-01-01

Abstract

Abstract: We evaluated intratumoral heterogeneity of 30 ductal breast carcinomas with HER2/neu amplification, scored by the American Society of Clinical Oncology/ College of American Pathologists (ASCO/CAP) criteria, and 3+ immunoexpression. High-grade (ratio > or =4.0) vs low-grade amplification (ratio >2.2 to <4.0) and chromosome 17 polysomy were also evaluated. On whole tissue sections, 20 tumors (67%) showed high-grade and 10 (33%) showed low-grade HER2/ neu amplification. Of 20 tumors with high-grade amplification, 14 (70%) showed no intratumoral genotypic heterogeneity; 6 (30%) showed at least 1 core with low-grade amplification. Of 10 cases with low-grade amplification, 6 (60%) showed no intratumoral heterogeneity; 4 (40%) showed chromosome 17 polysomy without gene amplification in 2 of 3 cores per case. Of 30 cases with gene amplification, 4 (13%) showed a "not-amplified pattern" in other parts of the tumor. The routine assessment of HER2/neu amplification using the ASCO/CAP criteria on whole tissue sections is not significantly confounded by intratumoral heterogeneity in breast cancer with high-grade amplification; however, genetic heterogeneity exists in a subset of breast carcinomas with low-grade amplification. The clinical relevance and impact on treatment outcome of intratumoral heterogeneity in breast cancer with low-grade HER2/neu amplification or chromosome 17 polysomy need further investigation.
breast cancer; Her-2; fluorescence in situ hybridization
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/328775
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