A direct relationship has been firmly established between cyclooxygenase-2 (COX-2) expression and malignant behavior in human melanoma. This report examines the relationship between COX-2 expression and tumor location, mitotic and proliferative indices, degree of T CD3 þ lymphocyte infiltration, overall survival, and frequency of recurrence and metastasis of 57 melanocytic tumors (25 oral and 32 cutaneous). COX-2 was highly or moderately expressed in 88% of oral neoplasms (22 of 25), whereas for their cutaneous counterparts, COX-2 expression was low or insignificant in 75% of cases (24 of 32). High and moderate COX-2 expression levels were observed in 73% of melanocytic tumors with a mitotic index ! 3 per 10 high-power fields (26 of 36), whereas in 81% of tumors with a mitotic index < 3 (17 of 21), expression was mild or absent. There were 41 cases with known clinical outcomes; of those showing high, moderate, and mild COX-2 expression, 83.3% (10 of 12), 37.5% (3 of 8), and 25% (2 of 8) died, respectively, whereas 100% of animals showing no COX-2 expression (13 of 13) were still alive at the last follow-up. COX-2 expression was statistically correlated with tumor location, mitotic and percentage Ki-67 proliferative indices, and overall survival, frequency of neoplastic recurrence and metastasis. Regression analysis also showed disease-specific predictive value for COX-2 expression for subjects with melanocytic neoplasms. Additionally, only high COX-2 expression showed significant differences in overall survival, in comparison with moderate, mild, or absent expression. These results suggest that high COX-2 expression may be considered a prognostic biomarker and potentially as a target for therapeutic and preventive strategies in canine melanocytic neoplasms. Keywords cyclooxygenase-2, canine, melanoma, prognosisCanine melanocytic neoplasms occur most frequently in the skin and oral cavity. Classically, body location is one criterion used to establish a prognosis of these tumors. 1,7,10,36 In the skin, melanocytic neoplasms account for 4 to 20% of all cutaneous neoplasms, of which fewer than 5% are malignant. 16,32 Yet canine oral melanomas account for 30 to 40% of all neoplasms in the head and are considered malignant, 36 with poorer prognosis and lower survival rates than their cutaneous melanocytic counterparts. The reasons for this more aggressive behavior are not clear. Recent data suggest that this malignancy may be due to a higher atypia and proliferation rate observed in oral melanomas.27,37 However, several reports suggest a lack of correlation between tumor location and clinical course. 6,20 Of the extensive number of factors used in human pathology to establish an accurate prognosis of melanocytic neoplasms, 40 the mitotic index and Ki-67 proliferation index are the factors that have shown the best correlation with clinical outcome of canine melanocytic neoplasms. 27,[34][35][36][37] Although the mitotic index is considered the most reliable feature for establishing the biological behavior of cu...
Feline mammary carcinomas are highly aggressive neoplasms. Several mechanisms are thought to be involved in their progression, including the loss of epithelial adhesion molecules. The present study was carried out on 21 adenomas and 139 mammary carcinomas. Of the carcinomas, 66 were not reported to have metastasized, while the remaining 73 had evidence of regional lymph node metastasis at the moment of diagnosis. The relationship was examined between the expression of the E-cadherin-b-catenin complex and basal (CK5/6, CK14) and luminal (CK8/18) cytokeratin expression. In the medical literature, carcinomas expressing basal cytokeratins are reported as having a poor prognosis in human breast cancer. Results revealed that preservation of the expression of E-cadherin and b-catenin is a significant feature of carcinomas without metastasis, whereas carcinomas with metastasis reveal the loss of one or both adhesion molecules. Additionally, basal cytokeratin expression was statistically associated with the presence of regional metastasis. Furthermore, the expression of E-cadherin-b-catenin was significantly correlated with the high expression of CK18 and low expression of CK5/6. Keywords feline mammary carcinoma, immunohistochemistry, E-cadherin, b-catenin, basal cytokeratinsMammary neoplasia is the third-most-common tumor type affecting female cats, following hemopoietic neoplasms and skin tumors. Malignancy is frequently reported and presents with local and distant metastases and high mortality rates. 42 Based on age, incidence, risk factors, histopathology, prognostic aspects, metastatic pattern, and response to therapy, feline mammary carcinomas have been proposed as a good model for human breast cancer. 2,42 Similar to reports in women, many veterinary studies describe regional lymph node involvement as one of the most important prognostic factors for feline mammary tumors. 11,16
The cadherin family of adhesion molecules regulates cell-cell interactions. N-cadherin is expressed by neural and fibroblast cells but not by normal epithelial cells. In human medicine, the role of N-cadherin in breast cancer remains controversial, but some studies have described the switch from E-cadherin to N-cadherin as a critical step in the malignant progression of neoplastic cells. The present study was carried out on 160 feline mammary tumors (21 adenomas and 139 carcinomas). The relationship between the immunohistochemical expression of N-cadherin in neoplastic epithelial cells and 2 established prognostic factors such as regional metastasis and tumor grade was examined. The results of the study showed a statistically significant relation between the expression of N-cadherin and the 2 prognostic factors, and also a reduced expression of E-cadherin in tumors that expressed N-cadherin.
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