Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University-UNESP, Botucatu, SP, Brazil.
Department of Morphology, Instituto de Biociências, São Paulo State University-UNESP, Botucatu, SP, Brazil.
PLoS One. 2018 Jun 12;13(6):e0199173. doi: 10.1371/journal.pone.0199173. eCollection 2018.
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.
前列腺腺癌（PC）中存在一种不常见的变体，其分泌细胞中核 p63 的表达不同于典型的基底表达，这种现象已在男性中报道。然而，这种现象的生物学行为和临床意义尚不清楚。在犬中，尚未描述这种不常见的 PC 亚型。在本研究中，研究了 90 例犬前列腺癌和 20 例正常前列腺组织（NT）中的 p63 免疫表达。通过免疫组织化学和/或 Western blot 检测，在选定的 26 例 PC 和 20 例 NT 中证实了 luminal 或基底细胞中 p63 的表达模式。与 15 例 p63 阴性（p63-）病例相比，11 例犬前列腺癌样本中存在分泌细胞中异常表达 p63（p63+）的样本中，研究了几种分子标志物（高分子量细胞角蛋白-HMWC、CK8/18、CK5、AR、PSA、嗜铬粒蛋白、NKX3.1、PTEN、AKT 和 C-MYC）。p63+样本对 CK5、HMWC 和 CK8/18 呈阳性，对 PSA、NKX3.1、PTEN 和嗜铬粒蛋白呈阴性。5 例 p63+PC 对 AR 呈阴性，其余 6 例样本的 AR 表达水平较低。相比之下，p63-PC 在所有 15 例样本中均表现出 AR 和 PSA 的阳性表达。只有 5 例 p63-PC 对 CK5 呈阳性。与正常组织相比，p63+和 p63-PC 样本的细胞质 AKT 表达和核 C-MYC 染色均升高。转移性（N=12）和非转移性（N=14）PC 对所有检测标志物的免疫表达均相似。与人类 PC 不同，犬前列腺癌中异常表达 p63 的 PC 表现出较高的 HMWC 和 CK5 表达水平和较低的 NKX3.1 表达水平。与典型的犬前列腺癌相比，犬 p63+PC 是一种非常罕见的 PC 群体，表现出明显的表型，包括 AR 和 PSA 阴性表达。尽管在有限数量的病例中，p63 的表达与犬前列腺癌的转移无关，但在存活时间较短的动物中观察到细胞质 p63 的表达，这与人类 PC 病例相似。
