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AN IMMUNOHISTOCHEMICAL STUDY OF THE PTEN/AKT PATHWAY INVOLVEMENT IN CANINE AND FELINE MAMMARY TUMOURS
AN IMMUNOHISTOCHEMICAL STUDY OF THE PTEN/AKT PATHWAY INVOLVEMENT IN CANINE AND FELINE
MAMMARY TUMOURS
Asproni P.[1], Millanta F.[1], Ressel L.[2], Vannozzi I.[1], Poli A.P.*[1]
[1]Università ~ Pisa, [2]Università ~ Liverpool
The PTEN/AKT pathway is strongly involved in cell metabolism, proliferation and survival. Its dysregulation
is implicated in several human cancers. The aim of this study was to investigate the role of this pathway in
canine (CMTs) and feline mammary tumors (FMTs) by immunohistochemistry (IHC).
Fifty CMTs (10 adenomas and 40 carcinomas) and 30 FMTs (30 carcinomas) were submitted to IHC to
evaluate PTEN, phospho-AKT and Rictor expression.
All the canine adenomas (100%), 25 of 40 (63%) canine carcinomas, and 7 of 30 (23%) FMTs were PTENpositive.
In dogs, no adenomas and 15 of 25 (37%) carcinomas expressed phospho-AKT, while 24 of 30
FMTs (82%) were phospho-AKT-positive. One of 10 (10%) canine adenomas (100%), 24 of 40 (60%) canine
carcinomas, and 20 of 30 (67%) FMTs were Rictor-positve. In dogs, PTEN correlated with complex
carcinomas, lower mitotic index, absence of lymphatic invasion and longer survival; phospho-AKT with
simple carcinomas, lymphatic invasion and poorer survival and Rictor with lymphatic invasion. In cats, PTEN
correlated with tubulopapillary carcinomas, lower mitotic index, absence of lymphatic invasion and better
survival, while phospho-AKT and Rictor with poorer survival. In CMTs, phospho-AKT inversely correlated
with PTEN expression and positively with Rictor. In FMTs, PTEN inversely correlated with phospho-AKT and
Rictor while phospho-AKT positively correlated with Rictor expression.
Our data show a strong PTEN/AKT pathway involvement in behavior worsening of CMT and FMTs. This data
could provide a rationale for further studies of this system in veterinary oncology to due prognostic and
therapeutic implications.
Jiang BH, Liu LZ. PI3K/PTEN signaling in angiogenesis and tumorigenesis. Adv Cancer Res. 2009;102:19-65.
Maniscalco L, Iussich S, de Las Mulas JM, et al. Activation of AKT in feline mammary carcinoma: a new
prognostic factor for feline mammary tumours. Vet J. 2012;191(1):65-71.
Ressel L, Millanta F, Caleri E, Innocenti VM, Poli A. Reduced PTEN protein expression and its prognostic
implications in canine and feline mammary tumors. Vet Pathol. 2009;46(5):860-868.
Patologia veterinaria/Oncologia comparata
Dog and cat, Mammary tumours, PTEN/AKT pathwa
Ehlers-Danlos syndrome associated with fatal spontaneous vascular rupture in a dog
A 7-month-old male cross breed dog was presented with hyperextensible skin and atrophic scarring. A diagnosis of Ehlers-Danlos syndrome was made based on clinical signs, histopathology and electron microscopy. Two weeks after presentation, the dog died suddenly. Post-mortem examination revealed haemothorax and rupture of the left subclavian artery. Histological findings, including Goldner's modified Masson's trichrome staining and transmission electron microscopy of the subclavian artery, revealed abnormalities in the structure and arrangement of collagen fibrils, suggesting that the defective collagen formation extended to the vasculature. To the authors' knowledge, this is the first report of Ehlers-Danlos syndrome with vascular involvement in animals
Valutazione di due metodiche per la determinazione delle immunoglobuline nel siero del puledro di asino sorcino crociato dell’Amiata
Studio retrospettivo su 26 casi di tumore delle guaine dei nervi periferici nel cane
Peripheral nerve sheath tumours (PNST) arise from the cells surrounding the axons of peripheral nerves. The term PNST has been proposed to include those neoplasms involving peripheral nerves and nerve roots because of their presumed common cell of origin, the Schwann cell, and similar biological behaviour. Twenty-six cases of canine PNSTs were reviewed. Data on
tumour location, history, clinical signs, physical and neurogical examination, imaging studies, and surgical treatment were accurately evaluated. All the subjects were included in a 2-years follow-up study to determine the disease free survival intervals, overall survival times, and the causes of death. Tumours were divided into three groups based on the surgeon’s description of tumour location at the time of surgery: tumours involving nerves of brachial or lumbosacral plexus (1° group; n=1); tumours involving nerves distal to the brachial or lumbosacral plexus (2° group; n=11), and tumour with subcutaneous localization (3° group; n=14). Representative portions of examined tumours were submitted to routine histological examination for tumour grading and to determine mitotic index and margin evaluation. Location of the tumor, macroscopic intraoperative observation of tumor’s infiltration along with histopathologic grading, seems to be useful data to predict tumor’s behavior
Espressione di recettori per estrogeno e progesterone nei tumori mammari della cagna e della gatta
Quantitative histologic evaluation reveals different degree of liver atrophy in cachectic and starved dogs
Cases of neglect in dogs are among the forensic cases submitted most commonly for postmortem examination. Starvation is a form of primary protein-energy malnutrition in which the availability of food is severely restricted or absent; cachexia is a form of protein-energy malnutrition secondary to progressive metabolic derangement during chronic diseases. Despite both conditions leading to an emaciated appearance of the cadaver, discrimination between the two is crucial in forensic cases. We hypothesized that among emaciated dogs, the degree of liver atrophy in starved animals is higher than in cachectic ones, and that this can be investigated microscopically, regardless of the degree of cadaver decomposition. We studied 46 animals: 23 starved, 11 cachectic, and 12 control dogs. Portal tracts were identified by the presence of a bile duct and associated vascular structures recognizable by a thin rim of collagen still visible regardless of the degree of cadaver decomposition. The number of portal tracts per lpf (10×) was used as an indirect measure of atrophy. The number of portal tracts in starved dogs was significantly higher (p < 0.01) compared to both cachectic and control dogs, indicating a higher degree of liver atrophy in starvation. Measuring the density of portal tracts offers a reliable additional tool for discrimination between starvation and cachexia
Expression of Vascular Endothelial Growth Factor in Canine Inflammatory and Non-inflammatory Mammary Carcinoma
Inflammatory mammary carcinoma (IMC) is the most aggressive type of mammary tumour in the dog and has been proposed as a model for human inflammatory breast cancer. The aim of this study was to investigate angiogenesis in canine IMC by immunohistochemical assessment of the expression of vascular endothelial growth factor (VEGF). Tissues from 19 cases of IMC were compared with tissues from 27 cases of invasive mammary carcinoma without inflammation (non-IMC). Immunohistochemical expression of oestrogen receptor (ER), progesterone receptor (PR) and HER-2 receptor was also assessed. VEGF was strongly expressed in all IMCs and the percentage of VEGF-immunoreactive tumour cells was significantly higher in IMC than in non-IMC (P=0.02). There was no difference in HER-2 receptor expression between IMC and non-IMC, and no IMC expressed ER or PR. These results suggest that VEGF may contribute to the high angiogenic phenotype of canine IMC and that this expression may underlie the tendency towards local and systemic metastasis of these tumours. (C) 2009 Elsevier Ltd. All rights reserved
Reduced PTEN Protein Expression and Its Prognostic Implications in Canine and Feline Mammary Tumors
Phosphatase and tensin homolog (PTEN) belongs to the group of gatekeeper tumor suppressor genes and is involved in multiple mechanisms leading to cellular defense against neoplastic transformation and progression. Twenty-four dogs and 17 cats were submitted to a 2-year follow-up study, and clinicopathologic features were recorded and compared with immunohistochemical PTEN staining. PTEN-negative status occurred in 33% of canine and 76% of feline mammary carcinomas. In canine mammary carcinomas, there was a significant (P < .05) correlation between loss of PTEN protein expression and simple carcinoma histotype, lymphatic vessel invasion, lymph node metastases, distant organ metastases, tumor dedifferentiation, tumor recurrence, and shorter overall survival. In feline mammary tumors, a significant correlation between loss of PTEN protein expression and lymphatic vessel invasion was found. Loss of PTEN expression could be a useful prognostic marker in canine mammary carcinomas
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