HER2 Overexpression and Cytogenetical Patterns in Canine Mammary Carcinomas.

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.

Pathological spectrum in recurrences of glioblastoma multiforme.

INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant brain tumour. Despite advances in treatment its prognosis remains poor. Histological features of GBM are well known. On the contrary histological description of recurrences is still not available. The aim of this study was to describe the morphological, immunohistochemical and molecular features of recurrent GBMs. METHODS: 25 recurrent GBMs, diagnosed after 2005, were collected. All patients had undergone an adjuvant treatment regimen (temozolomide and/or radiotherapy). All cases were immunostained using anti-GFAP, Olig2 and Nogo-A antisera. MGMT and IDH1 status was reassessed. Features of the recurrences were compared with those of primary GBMs, time of recurrence and survival. RESULTS: Recurrences were divided morphologically into three groups: 1) recurrences displaying the same features of primary GBM, were highly cellular, had the fastest progression and the worst prognosis; 2) recurrences changing dramatically morphological appearance, had a slightly longer survival, 3) poorly cellular recurrences, with sparse neoplastic cells intermingled with reactive and necrotic tissue, displayed the slowest progression and longer survival. MGMT and IDH1 status remained unchanged between primary tumours and recurrences. DISCUSSION: GBM histological subtypes display different reactions to adjuvant treatments, offering a possible role in predicting different recurrence and survival time.