An unusual variant of prostate adenocarcinoma (PC) expressing nuclear p63 in secretory cells instead of the typical basal expression has been reported in men. Nevertheless, the biological behavior and clinical significance of this phenomenon is unknown. In dogs, this unusual PC subtype has not been described. In this study, p63 immunoexpression was investigated in 90 canine PCs and 20 normal prostate tissues (NT). The p63 expression pattern in luminal or basal cells was confirmed in a selected group of 26 PCs and 20 NT by immunohistochemistry and/or Western blotting assays. Eleven canine PC samples aberrantly expressing p63 (p63+) in secretory cells were compared with 15 p63 negative (p63-) cases in the context of several molecular markers (high molecular weight cytokeratin-HMWC, CK8/18, CK5, AR, PSA, chromogranin, NKX3.1, PTEN, AKT and C-MYC). P63+ samples were positive for CK5, HMWC and CK8/18 and negative for PSA, NKX3.1, PTEN and chromogranin. Five p63+ PCs were negative for AR, and the remaining six samples had low AR expression. In contrast, p63- PC showed AR and PSA positive expression in all 15 samples. Only five p63- PCs were positive for CK5. Both p63+ and p63- PC samples showed higher cytoplasmic AKT expression and nuclear C-MYC staining in comparison with normal tissues. Metastatic (N = 12) and non-metastatic (N = 14) PCs showed similar immunoexpression for all markers tested. In contrast to human PC, canine PC aberrantly expressing p63 showed higher expression levels of HMWC and CK5 and lower levels of NKX3.1. Canine p63+ PC is a very rare PC group showing a distinct phenotype compared to typical canine PC, including AR and PSA negative expression. Although in a limited number of cases, p63 expression was not associated with metastasis in canine PC, and cytoplasmic p63 expression was observed in animals with shorter survival time, similar to human PC cases.

The PTEN, AR, MDM2 and p53 protein network plays a central role in the development of many human cancers, thus eliciting the development of targeted cancer therapeutics. Dogs spontaneously develop tumours, and they are considered a good model for comparative oncology initiatives. Due to the limited information on these proteins in canine tumours, this study aimed to investigate gene and protein alterations in PTEN, AR, MDM2 and p53 in canine prostate cancer (PC). Protein expression was evaluated by immunohistochemistry (15 normal, 22 proliferative inflammatory atrophy (PIA) and 19 PC samples) and Western blotting (2 normal prostate tissue, 2 BPH, 2 PIA samples and 2 PC samples) and gene expression by RT-qPCR (10 normal, 10 PIA and 15 PC samples) of formalin-fixed tissue. We identified nuclear and cytoplasmic expression of PTEN and p53 in all samples, with only nuclear staining found for MDM2 and AR. Our results revealed high expression of MDM2 in PC and PIA samples compared to normal samples, whereas PTEN, P53 and AR expression was down-regulated in PC compared to normal tissue. All tumour samples (n=19) showed loss of nuclear PTEN expression, and all cancer mimickers showed positive nuclear staining. Therefore, nuclear PTEN staining could be a good diagnostic marker for differentiating between malignant lesions and mimickers. Canine prostate carcinogenesis involves increased expression of MDM2 in association with decreased expression of PTEN, p53 and AR, such as occurs in hormone refractory PC in men. Thus, dogs may be an important model for studying advanced stage PC.

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Backgroundc-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines.ResultsEleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive.ConclusionThe present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer.Electronic supplementary materialThe online version of this article (10.1186/s12917-017-1304-0) contains supplementary material, which is available to authorized users.