| Full text | |
| Author(s): |
de Godoy Fernandes, Giovana
;
Pedrina, Bruna
;
de Faria Lainetti, Patricia
;
Kobayashi, Priscila Emiko
;
Govoni, Veronica Mollica
;
Palmieri, Chiara
;
de Moura, Veridiana Maria Brianezi Dignani
;
Laufer-Amorim, Renee
;
Fonseca-Alves, Carlos Eduardo
Total Authors: 9
|
| Document type: | Journal article |
| Source: | CANCERS; v. 13, n. 8, p. 17-pg., 2021-04-01. |
| Abstract | |
Simple Summary Prostatic diseases are important worldwide, being the prostate cancer (PC) the most common tumor in men. Among the factors associated with PC development, the preneoplastic lesions are well-recognized. Preneoplastic lesions are cellular morphological alterations, induced by different factors and present a potential to progression for PC. In this scenario, dogs are considered spontaneous models. Dogs naturally develops prostatic hyperplasia, preneoplastic lesions and PC. Among the preneoplastic lesions, the proliferative inflammatory atrophy (PIA) develops spontaneously in dogs. PIA is an epithelial lesion induced by prostatic chronic inflammation, leading to a proliferative atrophy of the prostate gland. Thus, this study aimed to perform a full PIA morphological, phenotypical and molecular characterization in dogs. After reviewing the archives of the veterinary pathology service, it was identified 171 dogs containing PIA in the prostate gland, and among the PC cases (N = 84), it was identified PIA lesions surrounding 60.7% of PC cases. Besides that, we identified loss of genes related to the maintenance of prostatic tissue and can predispose to malignant transformation. Moreover, mutations in androgen receptor gene were identified, demonstration alteration in DNA in PIA. Overall, these results support the hypothesis that PIA can be considered a preneoplastic lesion in canine prostate. Proliferative inflammatory atrophy (PIA) is an atrophic lesion of the prostate gland that occurs in men and dogs and is associated with a chronic inflammatory infiltrate. In this study, we retrospectively reviewed canine prostatic samples from intact dogs, identifying 50 normal prostates, 140 cases of prostatic hyperplasia, 171 cases of PIA, 84 with prostate cancer (PC), 14 with prostatic intraepithelial neoplasia (PIN) and 10 with bacterial prostatitis. PIA samples were then selected and classified according to the human classification. The presence of PIA lesions surrounding neoplastic areas was then evaluated to establish a morphological transition from normal to preneoplastic and neoplastic tissue. In addition, the expression of PTEN, P53, MDM2 and nuclear androgen receptor (AR) were analyzed in 20 normal samples and 20 PIA lesions by immunohistochemistry and qPCR. All PIA lesions showed variable degrees of mononuclear cell infiltration around the glands and simple atrophy was the most common histopathological feature. PIA was identified between normal glands and PC in 51 (61%) out of the 84 PC samples. PIA lesions were diffusely positive for molecular weight cytokeratin (HMWC). Decreased PTEN and AR gene and protein expression was found in PIA compared to normal samples. Overall, our results strongly suggest that PIA is a frequent lesion associated with PC. Additionally, this finding corroborates the hypothesis that in dogs, as is the case in humans, PIA is a pre neoplastic lesion that has the potential to progress into PC, indicating an alternative mechanism of prostate cancer development in dogs. (AU) | |
| FAPESP's process: | 12/18426-1 - Epigenetic evaluation of NKX3.1 and CDH1 and immunohistochemistry expression of C-MYC, NKX3.1 and E-cadherin on tissue microarray (TMA) of pre-neoplastic and neoplastic prostate of dogs |
| Grantee: | Carlos Eduardo Fonseca Alves |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 19/00497-9 - Morphological and phenotypic characterization of the canine prostatic carcinoma cells origin |
| Grantee: | Giovana de Godoy Fernandes |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |