Alterations of C-MYC, NKX3.1, and E-cadherin expression in canine prostate carcinogenesis

Abstract

The dog (canis lupus familiaris) is the only other species besides humans that develop spontaneous prostatic carcinomas (PCa) at a high frequency. The canine model is primarily utilized for the study of the PCa molecular mechanisms and provides a natural animal model for the study of potential therapies. In humans, the PCa frequently exhibits mutations in the C-MYC and a reduced expression of the E-cadherin and NKX3.1 proteins. This study's objective was to evaluate the NKX3.1, C-MYC, and E-cadherin expression in the canine normal prostate, benign prostatic hyperplasia (BPH), proliferative inflammatory atrophy (PIA) and PCa and to verify differences in expression and subcellular localization of these proteins in the prostatic carcinogenesis. A tissue microarray (TMA) slide was constructed, and immunohistochemistry with antibodies raised against C-MYC, NKX3.1, E-cadherin and p63 was performed using the peroxidase and DAB methods. The C-MYC protein expression was elevated in the cytoplasm and nuclei of the canine PCa and PIA compared with the normal prostate (P = 0.004. The NKX3.1 protein expression was reduced in 94.75% of the PCa and 100% of the PIA compared with the normal prostate (P = 0.0022). In fact, the expression of E-cadherin trended towards a decrease in carcinomas when compared to normal prostate and PIA. By immunohistochemistry, more p63-positive basal cells were observed in the PCa and PIA when compared with the normal prostate (P = 0.0002). This study has demonstrated that the carcinogenesis of canine prostatic tissue may be related to basal cell proliferation, the gain of C-MYC function and the loss of NKX3.1 protein expression.

Nectin‐4 and p63 immunohistochemical expression in canine prostate tumourigenesis

“…17 The expression of both p63 isoforms is dysregulated in several human and canine tumours including prostate cancer. [18][19][20] In this respect, several studies have investigated p63 expression in canine prostate carcinomas (PCs), [19][20][21][22][23] revealing that p63+ canine PCs represent a very rare PC group showing a distinct phenotype compared to typical canine PCs. 20 At the molecular lever, Nectin-4 and p63 are regulated by and regulate Interferon Regulatory Factor 6 (IRF6) protein in differentiated keratinocytes.…”

Electrochemotherapy with bleomycin associated with doxorubicin induces tumor regression and decreases the proliferative index in canine cutaneous squamous cell carcinomas

“…The immunoexpression levels of BAX, Bcl-2 and Ki67 were established by counting the number of stained cells and considering the number of positive cells in relation to the total number of cells inside the ocular grid per five random high-power fields (400x). The samples were classified as 0 (absence of stained cells), 1 (< 10% stained cells), 2 (10-25% stained cells), 3 (26-50% stained cells) and 4 (> 50% stained cells) according to Fonseca-Alves et al [44]. For the evaluation of the scores, cytoplasmic staining for BAX and Bcl-2 and nuclear staining for Ki67 were considered.…”

Co-localization of PTEN and E-cadherin in canine mammary hyperplasias and benign and malignant mammary tumors

“…Abnormal E-cadherin expression has been detected in several human carcinomas, such as digestive tract (Yun et al, 2014), urogenital (Li et al, 2011;Keck et al, 2013;Chang et al, 2014), lung (Bremnes et al, 2002) and cervical (Li et al, 2011) carcinomas. In canine oncology, E-cadherin expression has been investigated in several cancers and particularly in colorectal (Aresu et al, 2010), Merkel cell (Gil da Costa et al, 2010), testicular (Ciaputa et al, 2014), prostate (Fonseca-Alves et al, 2013) oral squaqmous cell (Mestrinho et al, 2014) and thyroid (Campos et al, 2014) carcinomas and tumors, in mammary tumours (Brunetti et al, 2003, Gama andSchmitt 2012;Yoshida et al, 2014), These reports confirmed E-cadherin membranous immunolocalization as the normal expression (Sarli et al, 2004), while cytoplasmic and nuclear location are linked to a downregulation of its tumor suppressor role (Chetty and Serra, 2008).…”