Prognostic evaluation of feline mammary carcinomas: a review of the literature.

A large number of studies have investigated feline mammary tumors in an attempt to identify prognostic markers and generate comparative analyses with human breast cancer. Nevertheless, a retrospective base of assessments and the lack of standardization in methodology and study design have caused weakness in study results, making comparison difficult. We examined feline mammary tumor publications and evaluated postulated prognostic parameters according to the recently published "Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology." Using these criteria, we determined with statistically significant reliability that prognostic parameters for feline mammary tumors are tumor grading and lymph node/lymphovascular invasion. Furthermore, tumor subtype, size, and staging are worthy of further standardized investigation. We present statistical significance for each studied parameter as well as its relevance to disease progression and survival. Our evaluation suggests that marker expression (ie, Ki67, HER2, ER) may provide relevant information applicable for therapeutic predictions; however, consensus efforts and protocol standardization are needed. We identify and discuss major points of concern--such as sample preservation and selection, standardization of immunohistochemical protocols, and evaluation of results--to provide support for subsequent reliable analyses.

The dog as a natural animal model for study of the mammary myoepithelial basal cell lineage and its role in mammary carcinogenesis.

Basal-like tumours constitute 2-18% of all human breast cancers (HBCs). These tumours have a basal myoepithelial phenotype and it has been hypothesized that they originate from either myoepithelial cells or mammary progenitor cells. They are heterogeneous in morphology, clinical presentation, outcome and response to therapy. Canine mammary carcinomas (CMCs) have epidemiological and biological similarities to HBCs, are frequently biphasic and are composed of two distinct neoplastic populations (epithelial and myoepithelial). The present study evaluates the potential of CMCs as a natural model for basal-like HBCs. Single and double immunohistochemistry was performed on serial sections of 10 normal canine mammary glands and 65 CMCs to evaluate expression of cytokeratin (CK) 8/18, CK5, CK14, α-smooth muscle actin (SMA), calponin (CALP), p63 and vimentin (VIM). The tumours were also evaluated for Ki67 and human epidermal growth factor receptor (HER)-2 expression. A hierarchical model of cell differentiation was established, similar to that for the human breast. We hypothesized that progenitor cells (CK5(+), CK14(+), p63(+) and VIM(+)) differentiate into terminally-differentiated luminal glandular (CK8/18(+)) and myoepithelial (CALP(+), SMA(+) and VIM(+)) cells via intermediary luminal glandular cells (CK5(+), CK14(+) and CK8/CK18(+)) and intermediary myoepithelial cells (CK5(+), CK14(+), p63(+), SMA(+), CALP(+) and VIM(+)). Neoplastic myoepithelial cells in canine complex carcinomas had labelling similar to that of terminally-differentiated myoepithelial cells, while those of carcinomas-and-malignant myoepitheliomas with a more aggressive biological behaviour (i.e. higher frequency of vascular/lymph node invasion and visceral metastases and higher risk of tumour-related death) were comparable with intermediary myoepithelial cells and had significantly higher Ki67 expression. The majority of CMCs examined were negative for expression of HER-2. The biphasic appearance of CMCs with involvement of the myoepithelial component in different stages of cell differentiation may help to define the role of myoepithelial cells in the mammary carcinogenetic process and the heterogeneous nature of basal-like HBCs.

Proposed classification of the feline "complex" mammary tumors as ductal and intraductal papillary mammary tumors.

When compared with the canine species, feline mammary tumors (FMTs) are much less heterogeneous, with a predominance of simple malignant neoplasm. Benign FMTs are rare, and it is unclear if complex and mixed tumors exist in the feline. In this study, we selected for immunohistochemical analyses 12 FMTs that had unusual histologic features. A group of 8 (2 benign and 6 malignant) FMTs showed a biphasic epithelial/myoepithelial population and a very regular cord-like distribution in a "Chinese lettering" pattern, within ectatic ducts. A second group (2 benign and 2 malignant) had an intraductal epithelial papillary growth pattern with a basally located monolayer of myoepithelial cells and a supporting fibrovascular stroma. The myoepithelial component always produced a standard immunohistochemical signature. All malignancies were grade I, and the subjects were all alive at 1 year postdiagnosis. On the basis of their morphology, we propose that they be classified as feline ductal adenoma/carcinoma and feline intraductal papillary adenoma/carcinoma, respectively. They overlap with their canine counterparts and lack the typical myoepithelial differentiation patterns seen in canine complex neoplasms, and therefore, the term complex should be avoided in felines. This study will add new information on FMT classification and be useful for prognostic studies.

Immunohistochemical expression of E-cadherin and ß-catenin in feline mammary tumours.

E-cadherin and ß-catenin have been studied in carcinogenesis and tumour progression and reduced membrane expression of these molecules in canine mammary tumours has been associated with a poor prognosis. The present study investigated immunohistochemically the expression of E-cadherin and ß-catenin in 53 mammary tumours and 48 hyperplastic or dysplastic lesions from 57 queens. E-cadherin and ß-catenin expression was membranous in all samples and there was a significant decrease in expression in malignant tumours and metastases. Cytoplasmic expression of both markers was inversely correlated to the membrane localization. ß-catenin nuclear labelling was detected in one lymph node metastasis (60% positive cells) and in the basal/myoepithelial cells of 6/7 ductal tumours. No correlation with survival was found for either marker. These results confirm the role of these proteins in maintaining tissue architecture and in inhibiting cell invasiveness and potentially indicate the oncogenic potential of the Wnt/ß-catenin transduction pathway in feline mammary tumours. In addition, specific independent expression of ß-catenin in the nuclei of basal/myoepithelial cells might suggest that this molecule is involved in regulation of the mammary stem/pluripotent cell component. Further studies should include more cases of benign mammary neoplasia and further investigate ß-catenin nuclear expression in ductal tumours.

A huge ovarian cyst in a hysterectomized bitch.

A 11-year-old, spayed, female mixed breed-dog was presented with an abdominal mass that was detected 1 month ago. Upon abdominal palpation a large, firm, oval shaped, movable mass was found in the mid-abdominal region. Survey radiograph of the abdomen demonstrated an oval soft tissue dense mass located on the right side of the abdominal cavity. A large, heteregenous and cystic mass with solid components occupying the majority of the abdomen and a small, cystic mass with solid components caudal to the left kidney were identified by transabdominal ultrasonography. Computed tomography scans revealed bilateral ovarian masses, and a small volume of retroperitoneal fluid on the right side. A cystic, but otherwise solid mass located in the right ovary and small retained left ovary encapsulated in the ovarian bursa were excised surgically by midline laparotomy. Histopathological examination of the excised mass from the right side revealed a large cystic structure consistent with an ovarian cyst and multiple corpora lutea and follicles at different maturational stages were detected in the left ovary. The precise origin of the ovarian cyst could not be determined by morphological appearance. Immunohistochemical staining suggested a cyst of surface epithelial origin. At re-examination 6 months after the surgery, the bitch appeared healthy and the clinical findings were all normal. To our knowledge, the cyst described here is the largest reported in an incompletely ovariohysterectomized bitch.

An Immunohistochemical study of HER-2 expression in feline mammary tumours.

The aim of the present study was to evaluate HER-2 expression in feline mammary tumours. Five different immunohistochemical protocols were tested with 73 feline mammary carcinomas (MCs), 10 mammary adenomas and 73 hyperplastic or dysplastic mammary lesions. The histological features of these lesions, clinical follow-up and expression of Ki-67 and p53 were also examined. With an optimized immunohistochemical protocol, HER-2 overexpression was detected in only four of the 73 (5.5%) MCs and did not correlate with histological classification or with the 1 year post-surgical clinical outcome. No correlation was found between the expression of Ki-67 or p53 and HER-2. Five of the 73 (6.8%) hyperplastic or dysplastic lesions and one of the 10 (10%) mammary adenomas were HER-2 positive. These results suggest that HER-2 may not play as significant role in mammary carcinogenesis and prognosis in cats as it does in human patients.

E-cadherin and ß-catenin expression in canine colorectal adenocarcinoma.

E-cadherin and its associated cytoplasmic proteins, including ß-catenin, have been examined as potential oncogenic markers due to the significant correlation between tumour dedifferentiation and the invasive capacity of epithelial tumours. The purpose of this study was to evaluate the expression of E-cadherin and ß-catenin in canine colorectal cancer using immunohistochemistry and to examine the relationship between this expression and various clinicopathological variables. The expression pattern of E-cadherin and ß-catenin was investigated in 44 colorectal canine carcinomas. In the intestinal mucosa of noncancerous areas, epithelial cells demonstrated equally strong membranous expression of E-cadherin and ß-catenin localised to the cell-cell junctions. Reduced expression of E-cadherin and ß-catenin was demonstrated in 75% and 81.8% of the colorectal carcinoma cases, respectively. The down-regulation of both E-cadherin and ß-catenin was correlated with decreased differentiation and increased tumour grade. In addition, the expression of ß-catenin was correlated with tumour size. These results suggest that dysfunction of the E-cadherin-catenin complex starts in the early stages of carcinogenesis and that the disruption of the tissue architecture is progressively associated with the invasion of the tumour.

Systemic fatal type II coronavirus infection in a dog: pathological findings and immunohistochemistry.

A case of fatal systemic coronavirus infection is described in a 53-day-old Pekinese dog. Pathological findings and immunohistochemical identification using a monoclonal anti-canine Coronavirus antibody are included. Visceral lesions consisted of extensive fibrinopurulent bronchopneumonia, multiple renal cortical infarcts, severe coalescing centrilobular hepatic fatty change with minimal random hepatic necrosis, and multifocal splenic haemorrhage with lymphoid depletion. Moderate chronic diffuse enteritis was associated with intraluminal adult ascarids. Identification of type I and type II coronavirus in this subject had been previously confirmed by genotype-specific real-time reverse transcription-polymerase chain reaction (RT-PCR) assays of the intestinal contents, while only Coronavirus type II was detected in visceral organs. This case represents the first description of morphological lesions associated with a type II pantropic fatal coronavirus infection in the dog.