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Underexpression of p27/Kip in thyroid papillary microcarcinomas with gross metastatic disease
Mark L C Khoo1, Jeremy L Freeman, Ian J Witterick
1Department of Pathology, University Health Network, 610 University Ave, Suite 4-302, Toronto, Ontario, Canada M5G 2M9.
Objective:
Papillary microcarcinomas (PMCs) of the thyroid (measuring less than 1 cm in maximum dimension) are extremely common incidental histologic findings, and most of these tumors are not considered clinically significant. However, rare PMCs behave aggressively and metastasize early, giving rise to clinically significant metastatic disease. We hypothesized that p27 and MIB-1/Ki-67 immunoreactivity would allow us to identify this small subgroup of PMCs that have the potential to behave aggressively.
Methods:
We reviewed the histopathology reports of 2000 patients who underwent thyroid surgery at our institution between 1995 and 1999 and identified 22 patients who presented with gross regional metastases from a primary PMC. The primary and metastatic tumors were stained for ret, p53, p27, and MIB-1 using the avidin-biotin-peroxidase complex technique. A control group of 33 nonmetastasizing PMCs was also analyzed.
Results:
Immunoreactivity for ret, p53, and MIB-1 showed no difference between metastasizing and nonmetastasizing PMCs. In most tumors, ret was present, while p53 immunoreactivity was absent in all tumors. MIB-1 staining was present in a small number of cells in both groups of tumors. Immunoreactivity for p27 was quantitated by the intensity of expression as well as the distribution of positive cells within each tumor. All tumors showed lower p27 expression than normal thyroid tissue. However, metastasizing PMCs demonstrated a significantly lower expression of p27 than nonmetastasizing PMCs (P<.001).
Conclusion:
Our results suggest that p27 immunohistochemical analysis may be a valuable diagnostic tool in predicting aggressive potential in PMCs.
Insights
Papillary microcarcinomas (PMCs) are common thyroid tumors. Lower p27 expression in PMCs indicates a higher risk of aggressive behavior and metastasis, aiding in risk stratification.
Area of Science:
- Endocrinology
- Oncology
- Pathology
Background:
- Papillary microcarcinomas (PMCs) are small thyroid tumors, often found incidentally.
- While generally indolent, a subset of PMCs exhibit aggressive behavior and metastasize.
- Identifying aggressive PMCs is crucial for appropriate clinical management.
Purpose of the Study:
- To investigate the utility of p27 and MIB-1/Ki-67 immunoreactivity in distinguishing aggressive PMCs.
- To determine if these markers can predict the metastatic potential of PMCs.
Main Methods:
- Histopathology reports of 2000 thyroid surgery patients were reviewed.
- 22 patients with metastatic PMCs and 33 with non-metastasizing PMCs were identified.
- Tumors were analyzed for ret, p53, p27, and MIB-1 expression using immunohistochemistry.
Main Results:
- No significant difference in ret, p53, or MIB-1 expression between metastasizing and non-metastasizing PMCs.
- All PMCs showed lower p27 expression than normal thyroid tissue.
- Metastasizing PMCs exhibited significantly lower p27 expression compared to non-metastasizing PMCs (P<.001).
Conclusions:
- Reduced p27 expression is associated with aggressive behavior in PMCs.
- Immunohistochemical analysis of p27 may serve as a predictive marker for PMC aggressiveness.
- This finding could improve the diagnostic capability for identifying high-risk PMCs.