Aberrant P-cadherin expression is associated to aggressive feline mammary carcinomas.

BACKGROUND: Cadherins are calcium-dependent cell-to-cell adhesion glycoproteins playing a critical role in the formation and maintenance of normal tissue architecture. In normal mammary gland, E-cadherin is expressed by luminal epithelial cells, while P-cadherin is restricted to myoepithelial cells. Changes in the expression of classical E- and P-cadherins have been observed in mammary lesions and related to mammary carcinogenesis. P-cadherin and E-cadherin expressions were studied in a series of feline normal mammary glands, hyperplastic/dysplastic lesions, benign and malignant tumours by immunohistochemistry and double-label immunofluorescence. RESULTS: In normal tissue and in the majority of hyperplastic/dysplastic lesions and benign tumours, P-cadherin was restricted to myoepithelial cells, while 80% of the malignant tumours expressed P-cadherin in luminal epithelial cells. P-cadherin expression was significantly related to high histological grade of carcinomas (p <0.0001), tumour necrosis (p = 0.001), infiltrative growth (p = 0.0051), and presence of neoplastic emboli (p = 0.0401). Moreover, P-cadherin positive carcinomas had an eightfold likelihood of developing neoplastic emboli than negative tumours. Cadherins expression profile in high grade and in infiltrative tumours was similar, the majority expressing P-cadherin, regardless of E-cadherin expression status. The two cadherins were found to be co-expressed in carcinomas with aberrant P-cadherin expression and preserved E-cadherin. CONCLUSIONS: The results demonstrate a relationship between P-cadherin expression and aggressive biological behaviour of feline mammary carcinomas, suggesting that P-cadherin may be considered an indicator of poor prognosis in this animal species. Moreover, it indicates that, in queens, the aberrant expression of P-cadherin is a better marker of mammary carcinomas aggressive behaviour than the reduction of E-cadherin expression. Further investigation with follow-up studies in feline species should be conducted in order to evaluate the prognostic value of P-cadherin expression in E-cadherin positive carcinomas.

Nuclear pleomorphism: role in grading and prognosis of canine mammary carcinomas.

Canine mammary tumours are highly heterogeneous in morphology and behaviour and successful clinical management requires robust prognostic factors. Histological grade, determined by the Nottingham nuclear pleomorphism scoring method, has been considered one of these factors. Despite the adoption of this method, it is unknown whether inter-observer agreement exists regarding the assessment of its parameters in canine mammary carcinomas (CMC). In this study, the agreement between two observers in scoring nuclear pleomorphism using the Nottingham method was evaluated in 89 cases of CMC. Histological evidence of vascular invasion and/or lymph node metastases (both early signs of tumour aggressiveness) was recorded. For 48 animals, two years of follow-up data were available. Nuclear pleomorphism was quantitatively assessed using a stereological method that allowed for an unbiased estimation of nuclear size and its variability by determining the volume-weighted mean nuclear volume (v¯v). Differences between the v¯v estimations and nuclear pleomorphism scores were evaluated. Additionally, the prognostic significance of clinicopathological features including nuclear score and v¯v was evaluated. A poor agreement between the two observers was obtained (κ value 0.46). Tumours scored as 1 and 2 presented similar v¯v values and only tumours that scored 3 presented significantly higher estimates. The v¯v value was not associated with vascular invasion and/or lymph node metastases, but was higher in tumours that progressed during follow-up. In multivariable analysis, only tumour size was an independent factor regarding evidence of aggressiveness and an optimal cut-off of 2.9 cm was defined.