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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
CYTOLOGIC GRADING OF CANINE AND FELINE SPINDLE-CELL SARCOMAS OF SOFT TISSUES AND ITS CORRELATION WITH HISTOLOGIC GRADING
LXVIII CONVEGNO SISVET, XI CONVEGNO AIPVET E XII CONVEGNO SIRA
214
CYTOLOGIC GRADING OF CANINE AND FELINE SPINDLE-CELL SARCOMAS OF SOFT TISSUES AND ITS
CORRELATION WITH HISTOLOGIC GRADING
Millanta F.*[1], Asproni P.[1], Romano E.[1], Aquino G.[2], Poli A.[1]
[1]Department of Veterinary Science, University of Pisa ~ Pisa, [2]"Ardenza" Veterinary Hospital ~ Livorno
The grading of soft tissue spindle cell sarcomas (STSCS) is considered more useful than histologic histotype
to assign a specific therapy and determine the prognosis in humans (Enzinger et al., 2001). Histologic
grading is considered an important prognostic factor in canine STSCS as it may predict the onset of local
recurrence and metastatic potential. In human pathology and in the veterinary practice, fine needle
aspiration aspiration cytology (FNAC) of soft tissue mass lesions can be an accurate and minimally invasive
method for the initial pathologic diagnosis of soft tissue masses. The aim of our study was to assess the
utility and the accuracy of the cytologic grading on FNAC smears, in comparison to the histologic grading in
STSCS
Over a period of 2 years (2009-2011) 33 cases of cytologically diagnosed STSCS (20 canine and 13 feline)
with a following histological diagnosis were retrospectively separately reviewed. The FNAC smears were
graded without prior knowledge of the histologic grade, using the scheme proposed by Weir et al., (1999),
which is a three-tier system based on nuclear atypia, nuclear overlap, mitosis, and necrosis. The
corresponding histological sections were graded using the Coindre et al.,(1988) criteria in a blind fashion.
The degree of concordance was established using the Cohen’s K coefficient. (Palmer et al., 2001).
In the canine SCSTS there was an overall cytologic and histologic concordance for grading in 12/20 cases
(60%). The concordance was observed in 4/8 (50%) cases of histologic grade 1, in 8/12 (67%) cases of
grade 2, and in 0 cases of grade 3. In the feline species the concordance was 11/13 cases (85%). The
concordance was observed in 5/6 (83%) tumors of histologic grade 1, in 4/4 (100%) tumors of grade 2, and
in 2/3 (66.6%) cases of grade 3. The overall concordance in the entire study population of canine and feline
STSCS was 70%. The gradewise concordance was 65% in grade 1 cases, 75% in grade 2 cases, and 66% in
grade 3 cases.
The overall concordance is quite similar to that reported in human literature. Although a wider population
is required to strengthen our findings, these results suggest that cytologic grading of STSCS obtained by
FNA may be a useful tool for therapeutic approaches and as a prognostic indicator.
Coindre KM, Nguyen BB, Bonichon F, et al. Cancer. 1988; 61:2305-2309
Enzinger FM, Weiss SW, Goldblum JR. Soft tissue tumors, 4th ed. St. Louis, Mosby; 2001: 10-13.
Palmer HE, Mukunyadzi P, Culbreth W, Thomas JR. Diagn Citopathol. 2001; 24(5):307-316
Weir MM, Rosemberg AE, Bell DA. Am J Clin Pathol, 1999; 112:784-790
diagnostic cytopathology, small animal oncology
cytologic grading, soft tissue sarcoma, dog and ca
A mammary gland chondrolipoma in the dog
A 12-year-old intact female dog was submitted to surgery to remove a well-circumscribed mass located near the left inguinal mammary gland. At histological examination, the mass was unencapsulated and composed by lobules of fat cells and scattered isles of cartilaginous tissue. Chondroblasts and chondrocytes showed moderate signs of atypia and often were located singularly or in small clusters within the stroma of the neoplasm. Immunohistochemical analysis revealed that cells were vimentin and S-100 positive, whereas no immunoreactivity was showed for cytokeratin, cytokeratin 5/6, cytokeratin 14, and P63. A diagnosis of chondrolipoma was made based on microscopic findings
A case of feline primary inflammatory mammary carcinoma: clinicopathological and immunohistochemical findings.
The clinicopathological and immunohistochemical findings of a primary feline mammary tumour with features similar to human and canine primary inflammatory carcinoma are described for the first time. The cat presented to the clinic for the rapid onset of oedema, severe erythema, local pain and warmth of the inguinal region, with a pustular-to-nodular cutaneous lesion in association with an ill-defined underlying mass. An epithelial malignant tumour was diagnosed by cytological investigation. Necropsy revealed a thickening of the skin with oedema of the subcutis in the right inguinal area, and regional and distant metastases. Histology showed an unencapsulated tubulopapillary proliferation of malignant epithelial cells, with a massive embolisation in the dermal lymphatics and a mild inflammatory infiltrate. Through immunohistochemistry, the tumour was found to be oestrogen (ER)-alpha-, androgen (AR)- and progesterone (PR)-negative; neoplastic cells were ER-alpha, AR-negative and focally PR-positive. An irregular, mild and focal HER-2 immunoreactivity was present (score +1, non-HER-2 overexpressing). The neoplastic cells were cyclo-oxygenase-2 and vascular endothelial growth factor positive
Amyloidosis in association with spontaneous Feline Immunodeficiency Virus infection
Tissues from 34 naturally feline immunodeficiency virus (FIV)-infected cats, 13 asymptomatic and 21 with signs of feline acquired immunodeficiency syndrome (F-AIDS), and 35 FIV-seronegative subjects were examined to determine the presence of amyloid deposits. Twenty experimentally FIV-infected cats and five specific pathogen free (SPF) control cats were also included in the study. Paraffin-embedded sections from kidney and other organs were submitted to histological and histochemical analysis and amyloid deposits were identified by a modified Congo Red stain and confirmed by electron microscopy to demonstrate the presence of amyloid fibrils, in amyloid positive glomeruli. In all positive cases, secondary amyloidosis was identified with the potassium permanganate pretreatment and amyloid type was further characterized by immunoistochemistry using primary antibodies against human AA and AL amyloids. Amyloid deposits were present in different tissues of 12/34 (35%) naturally FIV-infected cats (7 presenting FAIDS and 5 in asymptomatic phase) and in 1/30 FIV-seronegative cats. All the experimentally FIV-infected and SPF subjects showed no amyloid deposits. Amyloidosis has been yet reported in lentiviral infections, and the data here reported demonstrate the need, in naturally FIV-infected cats, to consider the presence of amyloidosis in differential diagnosis of hepatic and renal disorders to better assess the prognosis of the disease
A case of feline primary inflammatory mammary carcinoma: clinicopathological and immunohistochemical findings
The clinicopathological and immunohistochemical findings of a primary feline mammary tumour with features similar to human and canine primary inflammatory carcinoma are described for the first time. The cat presented to the clinic for the rapid onset of oedema, severe erythema, local pain and warmth of the inguinal region, with a pustular-to-nodular cutaneous lesion in association with an ill-defined underlying mass. An epithelial malignant tumour was diagnosed by cytological investigation. Necropsy revealed a thickening of the skin with oedema of the subcutis in the right inguinal area, and regional and distant metastases. Histology showed an unencapsulated tubulopapillary proliferation of malignant epithelial cells, with a massive embolisation in the dermal lymphatics and a mild inflammatory infiltrate. Through immunohistochemistry, the tumour was found to be oestrogen (ER)-alpha-, androgen (AR)- and progesterone (PR)-negative; neoplastic cells were ER-alpha, AR-negative and focally PR-positive. An irregular, mild and focal HER-2 immunoreactivity was present (score +1, non-HER-2 overexpressing). The neoplastic cells were cyclo-oxygenase-2 and vascular endothelial growth factor positive
Immunohistochemical expression of COX-2, MPGES-1, and EP-2 receptor in canine healthy and reactive bone tissues and canine osteosarcomas
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