PMID- 28752092 OWN - NLM STAT- MEDLINE DCOM- 20180405 LR - 20181113 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2017 DP - 2017 TI - Automated Image Analysis of HER2 Fluorescence In Situ Hybridization to Refine Definitions of Genetic Heterogeneity in Breast Cancer Tissue. PG - 2321916 LID - 10.1155/2017/2321916 [doi] LID - 2321916 AB - Human epidermal growth factor receptor 2 gene- (HER2-) targeted therapy for breast cancer relies primarily on HER2 overexpression established by immunohistochemistry (IHC) with borderline cases being further tested for amplification by fluorescence in situ hybridization (FISH). Manual interpretation of HER2 FISH is based on a limited number of cells and rather complex definitions of equivocal, polysomic, and genetically heterogeneous (GH) cases. Image analysis (IA) can extract high-capacity data and potentially improve HER2 testing in borderline cases. We investigated statistically derived indicators of HER2 heterogeneity in HER2 FISH data obtained by automated IA of 50 IHC borderline (2+) cases of invasive ductal breast carcinoma. Overall, IA significantly underestimated the conventional HER2, CEP17 counts, and HER2/CEP17 ratio; however, it collected more amplified cells in some cases below the lower limit of GH definition by manual procedure. Indicators for amplification, polysomy, and bimodality were extracted by factor analysis and allowed clustering of the tumors into amplified, nonamplified, and equivocal/polysomy categories. The bimodality indicator provided independent cell diversity characteristics for all clusters. Tumors classified as bimodal only partially coincided with the conventional GH heterogeneity category. We conclude that automated high-capacity nonselective tumor cell assay can generate evidence-based HER2 intratumor heterogeneity indicators to refine GH definitions. FAU - Radziuviene, Gedmante AU - Radziuviene G AD - National Center of Pathology, Affiliate of Vilnius University Hospital Santariskiu Clinics, P. Baublio 5, LT-08406 Vilnius, Lithuania. AD - Faculty of Natural Sciences, Vilnius University, M. K. Ciurlionio 27, LT-03103 Vilnius, Lithuania. FAU - Rasmusson, Allan AU - Rasmusson A AD - National Center of Pathology, Affiliate of Vilnius University Hospital Santariskiu Clinics, P. Baublio 5, LT-08406 Vilnius, Lithuania. FAU - Augulis, Renaldas AU - Augulis R AD - National Center of Pathology, Affiliate of Vilnius University Hospital Santariskiu Clinics, P. Baublio 5, LT-08406 Vilnius, Lithuania. AD - Faculty of Natural Sciences, Vilnius University, M. K. Ciurlionio 27, LT-03103 Vilnius, Lithuania. AD - Faculty of Medicine, Vilnius University, M. K. Ciurlionio 21, LT-03101 Vilnius, Lithuania. FAU - Lesciute-Krilaviciene, Daiva AU - Lesciute-Krilaviciene D AD - National Center of Pathology, Affiliate of Vilnius University Hospital Santariskiu Clinics, P. Baublio 5, LT-08406 Vilnius, Lithuania. AD - Faculty of Natural Sciences, Vilnius University, M. K. Ciurlionio 27, LT-03103 Vilnius, Lithuania. FAU - Laurinaviciene, Aida AU - Laurinaviciene A AD - National Center of Pathology, Affiliate of Vilnius University Hospital Santariskiu Clinics, P. Baublio 5, LT-08406 Vilnius, Lithuania. AD - Faculty of Medicine, Vilnius University, M. K. Ciurlionio 21, LT-03101 Vilnius, Lithuania. FAU - Clim, Eduard AU - Clim E AD - TissueGnostics, Vienna, Austria. FAU - Laurinavicius, Arvydas AU - Laurinavicius A AUID- ORCID: 0000-0001-9232-1730 AD - National Center of Pathology, Affiliate of Vilnius University Hospital Santariskiu Clinics, P. Baublio 5, LT-08406 Vilnius, Lithuania. AD - Faculty of Medicine, Vilnius University, M. K. Ciurlionio 21, LT-03101 Vilnius, Lithuania. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20170528 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - *Automation, Laboratory MH - Breast Neoplasms/*genetics/pathology MH - Carcinoma, Ductal, Breast/*genetics/pathology MH - Female MH - Humans MH - *In Situ Hybridization, Fluorescence/instrumentation/methods MH - Receptor, ErbB-2/*genetics PMC - PMC5511668 EDAT- 2017/07/29 06:00 MHDA- 2018/04/06 06:00 PMCR- 2017/05/28 CRDT- 2017/07/29 06:00 PHST- 2016/12/19 00:00 [received] PHST- 2017/03/20 00:00 [revised] PHST- 2017/04/26 00:00 [accepted] PHST- 2017/07/29 06:00 [entrez] PHST- 2017/07/29 06:00 [pubmed] PHST- 2018/04/06 06:00 [medline] PHST- 2017/05/28 00:00 [pmc-release] AID - 10.1155/2017/2321916 [doi] PST - ppublish SO - Biomed Res Int. 2017;2017:2321916. doi: 10.1155/2017/2321916. Epub 2017 May 28.