Abstract
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.
Highlights
Canine prostate cancer (PC) represents 13% of all prostatic disorders, and its aggressive behavior is associated with a high metastasis rate and poor prognosis [1,2]
Normal luminal human prostatic cells are negative for p63, uroplakin III and high molecular weight cytokeratin (HMWC) and present positivity for prostatic specific antigen (PSA), low weight cytokeratin, NKX3.1 and androgen receptor (AR) expression [6,7]
Among the luminal markers used in human prostatic pathology, we investigated CK8/18, PSA, NKX3.1 and AR protein expression
Summary
Canine prostate cancer (PC) represents 13% of all prostatic disorders, and its aggressive behavior is associated with a high metastasis rate and poor prognosis [1,2]. Human normal prostatic tissues present a continuous basal cell layer positive for p63. During carcinogenesis, the basal cell layer is lost, and typical human PC lacks p63 positive cells [4,5]. Normal luminal human prostatic cells are negative for p63, uroplakin III and high molecular weight cytokeratin (HMWC) and present positivity for prostatic specific antigen (PSA), low weight cytokeratin (cytokeratin 8 and 18), NKX3.1 and androgen receptor (AR) expression [6,7]. In normal canine prostatic tissues, a discontinuous basal cell layer and fewer basal cells [3,8,9] have been reported. Due to the discontinuity of the basal cell layer in normal canine prostate, basal cell markers have not been used for PC diagnosis in veterinary medicine [8]
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