Nectin‐4 and p63 immunohistochemical expression in canine prostate tumourigenesis

Abstract

Nectin‐4 is an E‐cadherin‐based adherens junction protein of normal epithelial cells, as well as a potent mediator of anchorage‐independent cancer colony formation. It is considered a tumour‐associated histological and serological marker in various human cancers. The transcription factor p63 is a basal cell marker in the normal prostate, involved in cell adhesion, as well as in the formation and survival of circulating tumour cell clusters. The aim of this study was to evaluate Nectin‐4 and p63 immunohistochemical expression in 42 canine prostate tissues including 2 normal prostates, 10 benign prostatic hyperplasias (BPHs), 30 prostatic carcinomas (PCs), 1 pulmonary and 1 lymph node metastasis. From normal to neoplastic tissues, Nectin‐4 showed a progressive switching from membranous (m‐Nectin‐4) to cytoplasmic (c‐Nectin‐4), regardless of the histological subtypes, except for lack of expression in solid PCs. Metastatic cells exhibited both strong membranous and cytoplasmic positivity. c‐Nectin‐4 expression was significantly (P < 0.0001) increased in PCs/metastasis compared to BPHs cases and a decrease (P < 0.05) of nuclear p63 immunostaining was also detected in the two groups. Furthermore, data showed a significant association (P < 0.05) between p63 and m‐Nectin‐4 distribution, although their colocalization was detected only in scattered cells by double immunofluorescence. Our results suggest the involvement of m‐Nectin‐4 in canine prostate tumourigenesis and metastatic potential, while the exact role of c‐Nectin‐4 expression detectable in primary PCs requires further investigations.

miR‐497 induces apoptosis by the IRAK2/NF‐κB axis in the canine mammary tumour

“…The results of HE staining and IHC experiments showed that the canine mammary tumours, especially invasive breast cancers, had different cell sizes and a large degree of atypia, and lower ERα‐ and p63‐positive rates and higher Ki67‐ and HK2‐positive rates were found in the CMT samples compared to control samples (Figure 1). Altogether, these data suggest that the epidemiological and pathological features of CMTs are similar to previous studies about CMT 1,28 …”

Histological and immunohistochemical investigation of canine prostate carcinoma with identification of common intraductal carcinoma component

“…In the few available canine studies which evaluated p63 in PCa, the tumours were characterized by rare or absent expression of p63, 19–21 with the exception of a very rare subtype of glandular PCa, which aberrantly expresses p63 21 . In the canine cases of the present study, p63 expression was limited to rare (<5%) cells in most (90%) PCa, which is in agreement with previous studies 20 . The remaining four cases, consisting of two PCa with squamous differentiation and two well differentiated, suspected UC, were characterized by strong expression of p63.…”

“…In benign, that is, normal as well as hyperplastic, canine prostates examined in the present study, basal cell staining confirmed the previously reported discontinuous basal cell layer in dogs 18–20 . In contrast to p63 and CK5/6, IHC for CK14 revealed only rare staining of basal cells.…”

“…When combining the basal cell markers (p63, HMWCK) and UPIII staining, most PCa were either triple negative or weakly positive in the present study. In triple negative PCa, UC cannot be excluded with certainty since these markers have limited sensitivities and because poorly differentiated human and canine urothelial or non‐urothelial, PCa are known to have only rare or absent expression of these markers 19,20,64 . Considering the known high specificity of UPIII, it can be assumed that UPIII positive tumours or tumour areas correspond to urothelial differentiation.…”

“… 13 , 14 , 15 , 16 , 17 This however cannot be applied to dogs since the canine prostate basal cell layer is discontinuous even in the benign gland. 18 , 19 In most PCa of men and dogs, the expression of basal cell markers is either absent or restricted to a low number of neoplastic cells, 19 , 20 , 21 with the exception of one rare subtype of p63 positive PCa. 19 , 21 P63 and HMWCK are also used as urothelial markers, and may, ideally together with additional prostate glandular (PSA, PSAP, NKX3.1) and urothelial (GATA3, CK7, CK20) markers, help to distinguish poorly differentiated human glandular prostatic from urothelial carcinoma (UC).…”