1. ¹Department of Pathology, National Cancer Center, Goyang, Gyeonggi, Korea
2. ²Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea
3. ³Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
4. ⁴Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea
5. ⁵Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
6. ⁶Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea
7. ⁷Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Correspondence: Dr SY Park, Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea. E-mail: sypmd@snu.ac.kr

Received 9 November 2007; Revised 16 February 2008; Accepted 18 February 2008; Published online 21 March 2008.

Abstract

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 (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, macrometastasis 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.