**5.6 Prostatic neoplasia**

Prostatic adenocarcinomas are a rare condition, affecting both castrated and non-castrated animals. They present a prevalence of 0.2–0.6% and have a predilection for animals with more advanced age, and the average age of an animal diagnosed with prostatic neoplasia is around 10 years [19]. Castrated dogs may present a greater chance of developing prostatic adenocarcinoma, being up to 2.38 times greater than non-castrated dogs [19]. In addition, prostatic carcinoma in dogs is androgen independent so castration is not a therapeutic possibility, except in cases associated with PH [16].

In the author's experience, intact dogs present a higher prevalence of prostate cancer (PC), and this can be related to our dog population. Usually, castration is not performed in male dogs. Thus, we have a majority population of intact dogs. In a previous study of our research group [20], we have described a tumor phenotype in 90 canines with PC, and all dogs (90/90) were intact. We did not find any PC in a castrated dog, probably because in our dog population, castration is not routinely performed.

The clinical signs associated with prostatic carcinoma are dysuria, tenesmus, hematuria, anorexia, and weight loss. In addition, through transrectal palpation, the prostate is most often enlarged and asymmetric, and the animal may or may not present pain [16]. Complementary tests such as ultrasound and X-ray should always be required to assess the extent of the neoplasm in both the prostate and possible metastasis. Common radiographic findings are prostatic enlargement, prostatic mineralization, sublumbar lymphadenopathy, axial skeletal metastasis, pulmonary metastasis, and appendicular skeletal metastasis [19].

In ultrasonography, the most common findings are prostatic enlargement, prostatic tissue mineralization, diffuse areas presenting hyperechogenicity, and irregular prostatic contour [19]. Areas of metastasis of prostatic carcinoma in descending order of incidence include the lungs, regional lymph nodes, liver, urethra, spleen, colon, rectum, urinary bladder, bones, heart, liver, and distal and adrenal lymph nodes [16].

The definitive diagnosis of prostatic carcinoma is made by means of cytology or prostate biopsy. Both techniques can be performed transabdominally with the aid of ultrasonography. There are different histological subtypes of prostatic adenocarcinoma, and the major challenge is the differentiation between urothelial and luminal origins of the undifferentiated subtypes. The castrated dogs are more prone to develop the most undifferentiated kinds of neoplasms and seem difficult

#### **Figure 5.**

*Canine prostate cancer. (A) Low-grade canine prostate cancer (Gleason score 6) composed by small glandular proliferation with tubules showing more than two layers with evident nucleoli. Hematoxylin and eosin (H&E) staining, 10×. (B) High-grade prostate cancer (Gleason score 8), showing moderate anisokaryosis, evident nucleoli, and mitosis. Hematoxylin and eosin (H&E) staining, 40×.*

**95**

**Figure 7.**

*Anatomy, Histology, and Physiology of the Canine Prostate Gland*

*Gross morphology of two canine prostate cancers. (A) Infiltrative prostate cancer, with the prostate gland showing a heterogeneous parenchyma, cystic areas, and necrosis. (B) A serial section of a prostate gland with a* 

*Protein-protein interaction (PPI) analysis using the canine data (copy number alteration provided by Amorim et al. [27]) and the human prostate cancer data from The Cancer Genome Atlas (TCGA). It is possible to evaluate the connectivity degree between gene alterations in human and dogs (triangles). Genes with deletion frequency higher than 30% (red triangles) and genes with developed drug targets are also observed.*

*DOI: http://dx.doi.org/10.5772/intechopen.81410*

*canine prostate cancer showing a well-delimited mass (arrows).*

**Figure 6.**

*Anatomy, Histology, and Physiology of the Canine Prostate Gland DOI: http://dx.doi.org/10.5772/intechopen.81410*

#### **Figure 6.**

*Veterinary Anatomy and Physiology*

Prostatic adenocarcinomas are a rare condition, affecting both castrated and non-castrated animals. They present a prevalence of 0.2–0.6% and have a predilection for animals with more advanced age, and the average age of an animal diagnosed with prostatic neoplasia is around 10 years [19]. Castrated dogs may present a greater chance of developing prostatic adenocarcinoma, being up to 2.38 times greater than non-castrated dogs [19]. In addition, prostatic carcinoma in dogs is androgen independent so castration is not a therapeutic possibility, except in cases

In the author's experience, intact dogs present a higher prevalence of prostate cancer (PC), and this can be related to our dog population. Usually, castration is not performed in male dogs. Thus, we have a majority population of intact dogs. In a previous study of our research group [20], we have described a tumor phenotype in 90 canines with PC, and all dogs (90/90) were intact. We did not find any PC in a castrated dog, probably because in our dog population, castration is not routinely

The clinical signs associated with prostatic carcinoma are dysuria, tenesmus, hematuria, anorexia, and weight loss. In addition, through transrectal palpation, the prostate is most often enlarged and asymmetric, and the animal may or may not present pain [16]. Complementary tests such as ultrasound and X-ray should always be required to assess the extent of the neoplasm in both the prostate and possible metastasis. Common radiographic findings are prostatic enlargement, prostatic mineralization, sublumbar lymphadenopathy, axial skeletal metastasis, pulmonary

In ultrasonography, the most common findings are prostatic enlargement, prostatic tissue mineralization, diffuse areas presenting hyperechogenicity, and irregular prostatic contour [19]. Areas of metastasis of prostatic carcinoma in descending order of incidence include the lungs, regional lymph nodes, liver, urethra, spleen, colon, rectum, urinary bladder, bones, heart, liver, and distal and adrenal lymph nodes [16]. The definitive diagnosis of prostatic carcinoma is made by means of cytology or prostate biopsy. Both techniques can be performed transabdominally with the aid of ultrasonography. There are different histological subtypes of prostatic adenocarcinoma, and the major challenge is the differentiation between urothelial and luminal origins of the undifferentiated subtypes. The castrated dogs are more prone to develop the most undifferentiated kinds of neoplasms and seem difficult

*Canine prostate cancer. (A) Low-grade canine prostate cancer (Gleason score 6) composed by small glandular proliferation with tubules showing more than two layers with evident nucleoli. Hematoxylin and eosin (H&E) staining, 10×. (B) High-grade prostate cancer (Gleason score 8), showing moderate anisokaryosis, evident* 

metastasis, and appendicular skeletal metastasis [19].

*nucleoli, and mitosis. Hematoxylin and eosin (H&E) staining, 40×.*

**5.6 Prostatic neoplasia**

associated with PH [16].

performed.

**94**

**Figure 5.**

*Gross morphology of two canine prostate cancers. (A) Infiltrative prostate cancer, with the prostate gland showing a heterogeneous parenchyma, cystic areas, and necrosis. (B) A serial section of a prostate gland with a canine prostate cancer showing a well-delimited mass (arrows).*

#### **Figure 7.**

*Protein-protein interaction (PPI) analysis using the canine data (copy number alteration provided by Amorim et al. [27]) and the human prostate cancer data from The Cancer Genome Atlas (TCGA). It is possible to evaluate the connectivity degree between gene alterations in human and dogs (triangles). Genes with deletion frequency higher than 30% (red triangles) and genes with developed drug targets are also observed.*

to differentiate an undifferentiated prostatic adenocarcinoma from an undifferentiated prostatic urothelial carcinoma [21]. Recently, the Gleason score was also proposed in canine prostatic pathology (**Figure 5**) [22].

Morphologically, canine PC can present an infiltrative growth pattern or form a prostatic mass (**Figure 6**). The infiltrative pattern can be difficult to differentiate from other prostatic diseases such as prostatitis and PH. Thus, in these cases, ultrasound examination can be challenging.

The treatment of prostatic adenocarcinoma is most often ineffective, making it palliative rather than curative. In addition, in most cases the diagnosis is made only at an advanced stage of the disease, making the prognosis even more reserved [1]. The results of chemotherapy and surgical protocols in cases of prostatic adenocarcinoma are unsatisfactory, not prolonging the life expectancy of the patient. Radiotherapy may be an option in cases where increased prostatic volume due to the tumoral mass is a problem for the animal, since this therapeutic option can cause reduction of the prostate volume but without increase in life expectancy [8].

Another important point to consider is if the animal is neutered or not. Castration or the use of finasteride may help in reducing the prostatic volume but

#### **Figure 8.**

*Ingenuity pathway analysis (IPA) of the canine copy number alteration data published by Amorim et al. [27]. Disruption of the ILK signaling pathway. Genes in green present a significant copy number loss compared to normal tissue.*

**97**

provided the original work is properly cited.

University—UNESP, Botucatu, Brazil

*Anatomy, Histology, and Physiology of the Canine Prostate Gland*

usually euthanasia must be taken into consideration [1].

without influence on the tumor mass. Due to the poor prognosis of this condition,

evaluated the genomic of transcriptomic alterations in canine PC. In human, the molecular subtype of the PC is very important for the patient prognosis. The recurrent *SPOP*, FOXA1, and IDH1 mutations, genic fusions (*ERG*, *ETV1/4*, and FLI1), activated PI3K/AKT/mTOR and MAPK pathway mutations, and germ line or somatic DNA-repair gene mutations (including *BRCA1/2*, *CDK12*, *ATM*, *FANCD2*, and *RAD51C*) (~20% of primary PC) represent different subtypes of human PC [23].

The genomic profiling of canine PC is poorly explored. Few previous studies have

Canine molecular alteration in E-cadherin, Caveolin-1, APC and β-catenin [24], NKX3.1 and c-Myc [3], c-KIT [25] and PTEN, TP53, MDM2, and AR expression [26] was previously described in literature. However, these studies have evaluated only gene expression. A recent study from our research group investigated the copy number alterations in canine PC [27]. We identified copy number loss in TP53 and PTEN and gain of MDM2, indicating the role of the TP53 pathway in the development of canine PC. Moreover, we identified many drug targets in canine PC, including VEGF and HER-2 (**Figure 7**) and imbalances in ILK signaling

The authors would like to thank Fundação de Amparo à Pesquisa do Estado de

São Paulo (FAPESP) for its financial support (#2015/25400-7).

Antonio Fernando Leis-Filho and Carlos E. Fonseca-Alves\*

School of Veterinary Medicine and Animal Science, Sao Paulo State

\*Address all correspondence to: carloseduardofa@hotmail.com

The authors have no conflict of interests.

*DOI: http://dx.doi.org/10.5772/intechopen.81410*

pathway (**Figure 8**).

**Acknowledgements**

**Conflict of interest**

**Author details**

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Anatomy, Histology, and Physiology of the Canine Prostate Gland DOI: http://dx.doi.org/10.5772/intechopen.81410*

without influence on the tumor mass. Due to the poor prognosis of this condition, usually euthanasia must be taken into consideration [1].

The genomic profiling of canine PC is poorly explored. Few previous studies have evaluated the genomic of transcriptomic alterations in canine PC. In human, the molecular subtype of the PC is very important for the patient prognosis. The recurrent *SPOP*, FOXA1, and IDH1 mutations, genic fusions (*ERG*, *ETV1/4*, and FLI1), activated PI3K/AKT/mTOR and MAPK pathway mutations, and germ line or somatic DNA-repair gene mutations (including *BRCA1/2*, *CDK12*, *ATM*, *FANCD2*, and *RAD51C*) (~20% of primary PC) represent different subtypes of human PC [23].

Canine molecular alteration in E-cadherin, Caveolin-1, APC and β-catenin [24], NKX3.1 and c-Myc [3], c-KIT [25] and PTEN, TP53, MDM2, and AR expression [26] was previously described in literature. However, these studies have evaluated only gene expression. A recent study from our research group investigated the copy number alterations in canine PC [27]. We identified copy number loss in TP53 and PTEN and gain of MDM2, indicating the role of the TP53 pathway in the development of canine PC. Moreover, we identified many drug targets in canine PC, including VEGF and HER-2 (**Figure 7**) and imbalances in ILK signaling pathway (**Figure 8**).

## **Acknowledgements**

*Veterinary Anatomy and Physiology*

to differentiate an undifferentiated prostatic adenocarcinoma from an undifferentiated prostatic urothelial carcinoma [21]. Recently, the Gleason score was also

Morphologically, canine PC can present an infiltrative growth pattern or form a prostatic mass (**Figure 6**). The infiltrative pattern can be difficult to differentiate from other prostatic diseases such as prostatitis and PH. Thus, in these cases,

The treatment of prostatic adenocarcinoma is most often ineffective, making it palliative rather than curative. In addition, in most cases the diagnosis is made only at an advanced stage of the disease, making the prognosis even more reserved [1]. The results of chemotherapy and surgical protocols in cases of prostatic adenocarcinoma are unsatisfactory, not prolonging the life expectancy of the patient. Radiotherapy may be an option in cases where increased prostatic volume due to the tumoral mass is a problem for the animal, since this therapeutic option can cause reduction of the prostate volume but without increase in life expectancy [8]. Another important point to consider is if the animal is neutered or not. Castration or the use of finasteride may help in reducing the prostatic volume but

*Ingenuity pathway analysis (IPA) of the canine copy number alteration data published by Amorim et al. [27]. Disruption of the ILK signaling pathway. Genes in green present a significant copy number loss compared to* 

proposed in canine prostatic pathology (**Figure 5**) [22].

ultrasound examination can be challenging.

**96**

**Figure 8.**

*normal tissue.*

The authors would like to thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for its financial support (#2015/25400-7).

### **Conflict of interest**

The authors have no conflict of interests.

### **Author details**

Antonio Fernando Leis-Filho and Carlos E. Fonseca-Alves\* School of Veterinary Medicine and Animal Science, Sao Paulo State University—UNESP, Botucatu, Brazil

\*Address all correspondence to: carloseduardofa@hotmail.com

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
