PMID- 36356060 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221127 IS - 2306-7381 (Electronic) IS - 2306-7381 (Linking) VI - 9 IP - 11 DP - 2022 Oct 22 TI - HER2 Overexpression and Cytogenetical Patterns in Canine Mammary Carcinomas. LID - 10.3390/vetsci9110583 [doi] LID - 583 AB - Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase receptor that promotes tumor cell growth and is implicated in the pathogenesis of human breast cancer. The role of HER2 in canine mammary carcinomas (CMCs) is not clear. Therefore, this study aimed to examine the protein expression and cytogenetic changes of HER2 and their correlation with other clinical-pathological parameters in CMC. We retrospectively selected 112 CMCs. HER2, ER, and Ki67 were assessed by immunohistochemistry. HER2 antibody validation was investigated by immunoblot on mammary tumor cell lines. Fluorescence in situ hybridization (FISH) was performed with probes for HER2 and CRYBA1 (control gene present on CFA9). HER2 protein overexpression was detected in 15 carcinomas (13.5%). A total of 90 carcinomas were considered technically adequate by FISH, and 8 out of 90 CMC (10%) were HER2 amplified, 3 of which showed a cluster-type pattern. HER2 overexpression was correlated with an increased number of HER2 gene copies (p = 0.01; R = 0.24) and overall survival (p = 0.03), but no correlation with ER, Ki67, grade, metastases, and tumor-specific survival was found. Surprisingly, co-amplification or polysomy was identified in three tumors, characterized by an increased copy number of both HER2 and CRYBA1. A morphological translocation-fusion pattern was recognized in 20 carcinomas (22%), with a co-localized signal of HER2 and CRYBA1. HER2 is not associated with clinical-pathological parameters of increased malignancy in canine mammary tumors, but it is suitable for studying different amplification patterns. FAU - Muscatello, L V AU - Muscatello LV AUID- ORCID: 0000-0003-4653-0624 AD - Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, 40064 Bologna, Italy. FAU - Gobbo, F AU - Gobbo F AUID- ORCID: 0000-0002-4082-4675 AD - Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, 40064 Bologna, Italy. FAU - Di Oto, E AU - Di Oto E AD - OACP IE Ltd., T12H1XY Cork, Ireland. FAU - Sarli, G AU - Sarli G AUID- ORCID: 0000-0001-6405-3484 AD - Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, 40064 Bologna, Italy. FAU - De Maria, R AU - De Maria R AD - Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy. FAU - De Leo, A AU - De Leo A AUID- ORCID: 0000-0002-3761-5135 AD - Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy. AD - Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy. FAU - Tallini, G AU - Tallini G AUID- ORCID: 0000-0003-0113-6682 AD - Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy. AD - Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy. FAU - Brunetti, B AU - Brunetti B AUID- ORCID: 0000-0002-2694-905X AD - Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, 40064 Bologna, Italy. LA - eng GR - RC-2022-2773377/Italian Ministry of Health/ PT - Journal Article DEP - 20221022 PL - Switzerland TA - Vet Sci JT - Veterinary sciences JID - 101680127 PMC - PMC9694975 OTO - NOTNLM OT - HER2 gene amplification OT - Ki67 OT - canine mammary carcinoma OT - estrogen receptor OT - fluorescence in situ hybridization OT - immunohistochemistry OT - tissue microarray COIS- The authors declare no conflicts of interest. EDAT- 2022/11/11 06:00 MHDA- 2022/11/11 06:01 PMCR- 2022/10/22 CRDT- 2022/11/10 14:05 PHST- 2022/08/25 00:00 [received] PHST- 2022/10/14 00:00 [revised] PHST- 2022/10/20 00:00 [accepted] PHST- 2022/11/10 14:05 [entrez] PHST- 2022/11/11 06:00 [pubmed] PHST- 2022/11/11 06:01 [medline] PHST- 2022/10/22 00:00 [pmc-release] AID - vetsci9110583 [pii] AID - vetsci-09-00583 [pii] AID - 10.3390/vetsci9110583 [doi] PST - epublish SO - Vet Sci. 2022 Oct 22;9(11):583. doi: 10.3390/vetsci9110583.