Genotypic Intratumoral Heterogeneity in Breast Carcinoma With HER2/neu Amplification

被引：90

作者：

Brunelli, Matteo ^{[1
]}

Manfrin, Erminia ^{[1
]}

Martignoni, Guido ^{[1
]}

Miller, Keith ^{[2
]}

Remo, Andrea ^{[1
]}

Reghellin, Daniela ^{[1
]}

Bersani, Samantha ^{[1
]}

Gobbo, Stefano ^{[1
]}

Eccher, Albino ^{[1
]}

Chilosi, Marco ^{[1
]}

Bonetti, Franco ^{[1
]}

机构：

[1] Univ Verona, Dipartimento Patol, I-37134 Verona, Italy

[2] UCL, UK Natl External Qual Assessment Scheme, London, England

来源：

AMERICAN JOURNAL OF CLINICAL PATHOLOGY | 2009年 / 131卷 / 05期

关键词：

Breast carcinoma; HER2/neu; Intratumoral heterogeneity; Fluorescence in situ hybridization; FISH; American Society of Clinical Oncology/College of American Pathologists guidelines; IN-SITU HYBRIDIZATION; GENE AMPLIFICATION; CHROMOSOME-17; POLYSOMY; PROTEIN EXPRESSION; HER-2/NEU STATUS; CANCER; FISH; OVEREXPRESSION; TRASTUZUMAB; IMPACT;

D O I：

10.1309/AJCP09VUTZWZXBMJ

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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 >= 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 (700) 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.

引用

页码：678 / 682

页数：5

共 36 条

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