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Published on: February 8, 2015
Loss of p27 expression in canine mammary tumors and their metastases
R Klopfleisch1, M Schütze, A D Gruber
1Department of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Strasse 15, 14163 Berlin, Germany. klopfleisch.robert@vetmed.fu-berlin.de
Abstract:
The p27 gene is a member of the cyclin-dependent kinase inhibitors, which arrest G1- to S-phase transition of the cell cycle. We have previously shown a significant reduction of p27 mRNA expression level in laser-microdissected mammary carcinomas and their lymph node metastases when compared to non-neoplastic mammary gland of the same dog. Here, p27 expression was analyzed on the protein level in non-neoplastic mammary gland, primary mammary carcinomas, their lymph node metastases and intravascular tumor cells of 49 dogs, adenomas of 49 dogs and non-neoplastic mammary gland of 98 dogs by immunohistochemistry. A significantly (p0.05) decreased percentage of p27 positive tissue samples was found when normal gland was compared with adenomas, carcinomas and lymph node metastases. Specifically, 91% of normal gland epithelium displayed nuclear p27 expression. In contrast, only 22% of the adenomas, 20% of carcinomas, 12% of lymph node metastases and 32% of intravascular tumor cells had p27 reactivity. Cell cycle control by p27 is therefore lost in the majority of canine mammary tumors. The lack of significant differences between benign and malignant mammary tumors indicates that decreased p27 expression is an early step in carcinogenesis of canine mammary tumors and hinders the use of p27 as a marker of malignancy for this tumor type.
Insights
The cell cycle inhibitor p27 (also known as cyclin-dependent kinase inhibitor 1B) is significantly reduced in canine mammary tumors. This loss of p27 protein expression occurs early in tumor development, suggesting it is not a reliable marker for malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Veterinary Medicine
Background:
- The p27 gene encodes a cyclin-dependent kinase inhibitor crucial for cell cycle regulation, specifically arresting the G1 to S-phase transition.
- Previous studies indicated reduced p27 mRNA levels in canine mammary carcinomas and metastases compared to normal mammary tissue.
- Understanding p27 protein expression is vital for elucidating cell cycle dysregulation in canine mammary tumorigenesis.
Purpose of the Study:
- To investigate p27 protein expression levels in various canine mammary lesions, including normal gland, adenomas, carcinomas, lymph node metastases, and intravascular tumor cells.
- To determine if decreased p27 expression is an early event in canine mammary tumor development.
- To assess the potential of p27 as a biomarker for distinguishing benign from malignant canine mammary tumors.
Main Methods:
- Immunohistochemistry was employed to analyze p27 protein expression.
- Tissue samples included non-neoplastic mammary gland (n=98), adenomas (n=49), primary mammary carcinomas (n=49), lymph node metastases (n=49), and intravascular tumor cells (n=49).
- Quantification of nuclear p27 positivity was performed across all sample types.
Main Results:
- A significant decrease in p27 positive tissue samples was observed in adenomas, carcinomas, and lymph node metastases compared to normal mammary gland.
- Normal mammary gland epithelium showed 91% nuclear p27 expression, contrasting sharply with adenomas (22%), carcinomas (20%), lymph node metastases (12%), and intravascular tumor cells (32%).
- No significant difference in p27 expression was found between benign (adenomas) and malignant (carcinomas, metastases) mammary tumors.
Conclusions:
- Cell cycle control mediated by p27 is compromised in the majority of canine mammary tumors.
- The reduction in p27 expression appears to be an early event in the carcinogenesis of canine mammary tumors.
- p27 is not a reliable marker for distinguishing malignancy in canine mammary tumors due to its decreased expression in both benign and malignant lesions.
