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
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
收藏
页码:678 / 682
页数:5
相关论文
共 36 条
[11]   Intratumoral heterogeneity of HER2/neu in breast cancer -: A rare event [J].
Hanna, Wedad ;
Nofech-Mozes, Sharon ;
Kahn, Harriette J. .
BREAST JOURNAL, 2007, 13 (02) :122-129
[12]   HER2+breast cancer [J].
Hicks, David G. ;
Kulkarni, Swati .
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2008, 129 (02) :263-273
[13]   Central HER2 IHC and FISH analysis in a trastuzumab (Herceptin) phase II monotherapy study:: assessment of test sensitivity and impact of chromosome 17 polysomy [J].
Hofmann, M. ;
Stoss, O. ;
Gaiser, T. ;
Kneitz, H. ;
Heinmoeller, P. ;
Gutjahr, T. ;
Kaufmann, M. ;
Henkel, T. ;
Rueschoff, J. .
JOURNAL OF CLINICAL PATHOLOGY, 2008, 61 (01) :89-94
[14]   The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer [J].
Hyun, C. L. ;
Lee, H. E. ;
Kim, K. S. ;
Kim, S-W ;
Kim, J. H. ;
Choe, G. ;
Park, S. Y. .
JOURNAL OF CLINICAL PATHOLOGY, 2008, 61 (03) :317-321
[15]   HER-2 testing in breast cancer using immunohistochemical analysis and fluorescence in situ hybridization - A single-institution experience of 2,279 cases and comparison of dual-color and single-color scoring [J].
Lal, P ;
Salazar, PA ;
Hudis, CA ;
Ladanyi, M ;
Chen, BY .
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2004, 121 (05) :631-636
[16]   Impact of polysomy 17 on HER-2/neu immunohistochemistry in breast carcinomas without HER-2/neu gene amplification [J].
Lal, P ;
Salazar, PA ;
Ladanyi, M ;
Chen, BY .
JOURNAL OF MOLECULAR DIAGNOSTICS, 2003, 5 (03) :155-159
[17]   Polysomy 17 in HER-2/neu status elaboration in breast cancer: Effect on daily practice [J].
Ma, Y ;
Lespagnard, L ;
Durbecq, V ;
Paesmans, M ;
Desmedt, C ;
Gomez-Galdon, M ;
Veys, I ;
Cardoso, F ;
Sotiriou, C ;
Di Leo, A ;
Piccart, MJ ;
Larsimont, D .
CLINICAL CANCER RESEARCH, 2005, 11 (12) :4393-4399
[18]   Response to cyclophosphamide, methotrexate, and fluorouracil in lymph node-positive breast cancer according to HER2 overexpression and other tumor biologic variables [J].
Ménard, S ;
Valagussa, P ;
Pilotti, S ;
Gianni, L ;
Biganzoli, E ;
Boracchi, P ;
Tomasic, G ;
Casalini, P ;
Marubini, E ;
Colnaghi, MI ;
Cascinelli, N ;
Bonadonna, G .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (02) :329-335
[19]   Quantitative justification of the change from 10% to 30% for human epidermal growth factor receptor 2 scoring in the American society of clinical Oncology/College of American pathologists guidelines:: tumor heterogeneity in breast cancer and its implications for tissue Microarray based assessment of outcome [J].
Moeder, Christopher B. ;
Giltnane, Jennifer M. ;
Harigopal, Malini ;
Molinaro, Annette ;
Robinson, Andrew ;
Gelmon, Karen ;
Huntsman, David ;
Camp, Robert L. ;
Rimm, David L. .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (34) :5418-5425
[20]   HER2 status and benefit from adjuvant trastuzumab in breast cancer [J].
Paik, Soonmyung ;
Kim, Chungyeul ;
Wolmark, Norman .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (13) :1409-1411