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Underexpression of p27/Kip in Thyroid Papillary Microcarcinomas With Gross Metastatic Disease
Mark L. C. Khoo, FRCS;
Jeremy L. Freeman, MD;
Ian J. Witterick, MD;
Jonathan C. Irish, MD;
Lorne E. Rotstein, MD;
Patrick J. Gullane, MD;
Sylvia L. Asa, MD, PhD
Arch Otolaryngol Head Neck Surg. 2002;128:253-257.
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.
From the Department of Otolaryngology, Mount Sinai Hospital, Toronto,
Ontario (Drs Khoo, Freeman, and Witterick), and the Departments of Otolaryngology
(Drs Irish and Gullane), Surgery (Dr Rotstein), and Pathology (Dr Asa), University
Health Network, University of Toronto, Ontario.
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