Abstract 5260: Genomic gains in prostatic carcinoma and proliferative inflammatory atrophy in dogs

Fonseca-Alves, Carlos Eduardo; Busso, Ariane Fidelis; Silveira, Sara Martoreli; Rogatto, Sílvia Regina; Amorim, Renée Laufer

doi:10.1158/1538-7445.am2012-5260

Cited by 4 publications

(3 citation statements)

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“…Additionally, comparative oncology studies between human and canine methodology standardization is required. We believe that canine carcinogenic process is similar to humans, although dogs show some particularities related with genetic alterations and protein localization (Alves et al 2014).…”

Section: Discussionmentioning

confidence: 83%

Association between decreased expression of estrogen receptor alpha, androgen receptor and phosphatase and tensin homolog immunoexpression in the canine prostate

et al. 2019

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Canine prostate gland is a hormonal dependent organ and its imbalance of estrogen and androgen receptor expressions are directly associated with the development of different diseases. Due to the lack of information regarding the behavior of the aforementioned receptors in canine prostate cancer (PC), this study aimed to identify estrogen receptor alpha (ERα), androgen receptor (AR), Ki67 and phosphatase and tensin homolog (PTEN) protein expressions in canine PC by immunohistochemistry. We found nuclear expression of ERα and AR in the epithelial cells of normal canine samples and a loss of protein expression in PC samples. Normal samples showed Ki67 expression in a few basal cells and the PC samples showed the highest mean of positive cells (253.1). Canine prostate cancer showed a high proliferative index, which was associated with independence of hormonal actuation. PTEN showed positive nuclear and cytoplasmic expression in normal canine samples and a loss in PC. Loss of ERα, AR and PTEN indicated that canine PC exhibits the same immunohistochemical phenotype as in human patients with PC resistant to hormonal therapy. Therefore, canine PC should be considered as a model to study human PC resistant to hormonal therapy.

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Section: Discussionmentioning

confidence: 83%

Association between decreased expression of estrogen receptor alpha, androgen receptor and phosphatase and tensin homolog immunoexpression in the canine prostate

et al. 2019

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“…Loss of E-cadherin expression has also been reported in canine PIA [15]. Normally dividing prostatic epithelial cells can lose E-cadherin during cell division and re-express the same protein after the replication is completed [17]. Thus, all these previous studies suggest the occurrence of several genomic and protein alterations in canine PIA, that favors its potential preneoplastic lesion.…”

Section: Introductionmentioning

confidence: 67%

Morphological and Molecular Characterization of Proliferative Inflammatory Atrophy in Canine Prostatic Samples

Fernandes

Pedrina

Lainetti

et al. 2021

Cancers

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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.

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“…Dogs are the only mammals besides humans that spontaneous develop androgen-independent prostatic carcinoma (PC) at a high frequency, and therefore, dogs are considered a natural model in which to study PC (LeRoy and Northrup, 2009;Ittmann et al, 2013). They may be used in pre-clinical studies of human PC, and research on new prognostic and predictive markers may benefit both species (LeRoy and Northrup, 2009;Alves et al, 2014). In dogs, PC is a disease with highly undifferentiated morphology and an aggressive behaviour associated with a high metastatic rate (Fonseca- Alves et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of NKX3.1 and C-MYC expression in canine prostatic cancer

Fonseca-Alves

Kobayashi

Laufer-Amorim

2018

Research in Veterinary Science

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NKX3.1/C-MYC cross-regulation has been reported in the normal human prostate, and loss of NKX3.1 and gain of C-MYC seem to be important events in prostate cancer development and progression. The dog can be an interesting model for human prostatic disease, and yet only one previous research study has shown deregulation of NKX3.1 and MYC in the canine prostate. To address the expression of NKX3.1 and C-MYC in different canine prostatic lesions, this study verified the gene and protein expression of NKX3.1 and C-MYC in normal canine prostatic tissues. We identified a 26 kDa band that corresponded to the NKX3.1 protein, while C-MYC showed a 50 kDa band on Western blotting analysis of all prostatic tissues. We observed that NKX3.1 protein and transcript were down-regulated in prostate cancer (PC) samples compared with non-neoplastic samples. We also observed that C-MYC protein was overexpressed in PC samples compared with normal (P = .001) and proliferative inflammatory atrophy (PIA) samples (P = .003). We found a positive correlation between NKX3.1 and C-MYC protein expression in normal and PIA samples. Interestingly, a negative correlation (NKX3.1 downregulation and MYC overexpression) was observed between NKX3.1 and MYC transcripts in PC. Thus, samples with higher C-MYC expression also exhibited higher NKX3.1 expression, which indicates the regulation of C-MYC by NKX3.1 protein. As in humans, these two genes and proteins were found to be related to canine prostate cancer. However, in contrast from what is observed in humans, in canine PC samples, the downregulation of NKX3.1 cannot be explained by DNA hypermethylation.

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Abstract 5260: Genomic gains in prostatic carcinoma and proliferative inflammatory atrophy in dogs

Cited by 4 publications

References 0 publications

Association between decreased expression of estrogen receptor alpha, androgen receptor and phosphatase and tensin homolog immunoexpression in the canine prostate

Association between decreased expression of estrogen receptor alpha, androgen receptor and phosphatase and tensin homolog immunoexpression in the canine prostate

Morphological and Molecular Characterization of Proliferative Inflammatory Atrophy in Canine Prostatic Samples

Evaluation of NKX3.1 and C-MYC expression in canine prostatic cancer

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