S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid.
The detection of papillary microcarcinomas of the thyroid is increasing due to frequent use of ultrasound and fine-needle aspiration biopsy. Although most of the papillary microcarcinomas remain quiescent and follow an indolent clinical course, some behave aggressively and metastasize early, giving rise to clinically significant disease. There have been few studies concerning factors predictive of lymph node metastasis in papillary microcarcinomas. We analyzed the expression of S100A4, cyclin D1, p27 and MUC1, the presence of the BRAF V600E mutation and the clinicopathological features of the tumors, including patient age, tumor size (>or=5 vs <5 mm), extrathyroidal extension, multifocality, histological subtype, sclerosis and encapsulation, in a series of 198 papillary microcarcinomas in relation to lymph node metastasis to determine the predictive factors of lymph node metastasis. On univariate analysis, tumor size of 5 mm or more, extrathyroidal extension, multifocality, sclerosis and the expression of S100A4 and cyclin D1 predicted lymph node metastasis, whereas patient age, expression of p27 and MUC1 and the BRAF V600E mutation did not. Moreover, tumor size 5 mm or more, multifocality and expression of S100A4, especially its strong expression in the invasive fronts, were significantly associated with macrometastasis and lateral node metastasis. On multivariate analysis, multifocality and expression of S100A4 were found to be common independent predictive factors of lymph node metastasis, macrometastases, and lateral node metastasis. In conclusion, S100A4 expression in papillary microcarcinomas may indicate the presence of nodal metastasis. Thus, S100A4 immunohistochemistry may be valuable for predicting metastatic potential in papillary microcarcinomas.
Min
Hye Sook
HS
Department of Pathology, National Cancer Center, Goyang, Gyenggi, Korea.
Choe
Gheeyoung
G
Kim
Sung-Won
SW
Park
Young Joo
YJ
Park
Do Joon
DJ
Youn
Yeo-Kyu
YK
Park
Seong Hoe
SH
Cho
Bo Youn
BY
Park
So Yeon
SY
D000231:Adenocarcinoma, Papillary / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D019938:Cyclin D1 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D018396:Mucin-1; D018809:Proliferating Cell Nuclear Antigen; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C413374:p27 antigen; D019938:Cyclin D1; C077591:S100A4 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf