Underexpression of p27/Kip in thyroid papillary microcarcinomas with gross metastatic disease.
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).


CONCLUSIONS
Our results suggest that p27 immunohistochemical analysis may be a valuable diagnostic tool in predicting aggressive potential in PMCs.
Khoo
Mark L C
ML
Department of Pathology, University Health Network, 610 University Ave, Suite 4-302, Toronto, Ontario, Canada M5G 2M9.
Freeman
Jeremy L
JL
Witterick
Ian J
IJ
Irish
Jonathan C
JC
Rotstein
Lorne E
LE
Gullane
Patrick J
PJ
Asa
Sylvia L
SL
D034961:Antigens, Nuclear; D002291:Carcinoma, Papillary / Q000737:chemistry* / Q000175:diagnosis; D029721:Drosophila Proteins; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000175:diagnosis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D034961:Antigens, Nuclear; D029721:Drosophila Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila