{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:20:30Z","timestamp":1789420830031,"version":"build-2803163510"},"reference-count":20,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2011,7,23]]},"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      To determine the frequency of\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma, and to identify clinicopathological features that characterise breast carcinomas with\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      530 invasive breast carcinomas were retrospectively analysed for\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity, and investigated for a potential association of\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity with other\n                      <jats:italic>HER2<\/jats:italic>\n                      FISH findings, clinicopathological parameters, oestrogen\/progesterone receptor expression and DNA cytometric parameters in breast carcinomas with an equivocal (2+) HER2 immunohistochemical score.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The overall frequency of\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity was 14.7% in a cohort of 218 consecutive breast carcinomas.\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity was most frequent in invasive breast carcinomas with an equivocal (2+) HER2 immunohistochemical score. Among the 151 carcinomas lacking\n                      <jats:italic>HER2<\/jats:italic>\n                      amplification, 16.1% showed\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity. In an extended cohort of 345 carcinomas with a (2+) HER2 score, the frequency of\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity was 41%, and was associated with the absence of\n                      <jats:italic>HER2<\/jats:italic>\n                      gene clusters, chromosome 17 polysomy, histological tumour grade, DNA ploidy category and 5c exceeding rate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity according to the ASCO\/CAP definition is frequent in breast carcinoma, and is most often present in carcinomas with an equivocal (2+) HER2 score. Many carcinomas with\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity have a negative\n                      <jats:italic>HER2<\/jats:italic>\n                      amplification status, although they contain a significant number of tumour cells with\n                      <jats:italic>HER2<\/jats:italic>\n                      gene amplification. Single cell scoring of the\n                      <jats:italic>HER2<\/jats:italic>\n                      \/17 centromeric probe (CEP17) ratio is necessary to identify carcinomas with\n                      <jats:italic>HER2<\/jats:italic>\n                      genetic heterogeneity, because they lack specific clinicopathological characteristics.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jclinpath-2011-200265","type":"journal-article","created":{"date-parts":[[2011,10,19]],"date-time":"2011-10-19T20:59:07Z","timestamp":1319057947000},"page":"1112-1116","source":"Crossref","is-referenced-by-count":94,"title":["<i>HER2<\/i>\n                    genetic heterogeneity in breast 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