S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid

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 (Z5 vs o5 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.

Prognostic value of cytoplasmic expression of S100A4 protein in endometrial carcinoma

“…Thus, its prognostic value has been suggested (14-16). There are several recent published studies on the correlation between the survival rate and the increased expression of S100A4 in other types of human malignancies (17)(18)(19)(20)(21)(22)(23). These reports suggest that S100A4 is associated with the aggressiveness of cancer and it may play a role in the pathogenesis of advanced-stage cancer.…”

“…It has been reported that the positive cytoplasmic expression of S100A irrespective of its nuclear expression has a prognostic value in many human malignancies (9,11,12,14,16,21,22). Kicuchi et al reported that S100A4 could translocate between the cytoplasm and nucleus in ovarian cancer cells (19).…”

“…S100A4 belongs to the S100 calcium binding protein family and may be characterized as a cytoplasmic protein that promotes cellular motility via direct interaction with myosin-IIA and also has functions in cell cycle progression. Its overexpression has been documented in breast (9)(10)(11)(12), gastric (13), colorectal (14)(15)(16), esophageal squamous cell (17) and gallbladder carcinoma (18), ovarian (19) and bladder cancer (20), papillary thyroid carcinoma (21,22) and non-small cell lung cancer (23). In addition, its upregulation has been associated with disease progression, metastasis and decreased patient survival.…”

Immunogenicity of HLA-A1-restricted peptides derived from S100A4 (metastasin 1) in melanoma patients

“…S100A4 expression has also been described in primary and metastatic melanoma [3,32,39]. Elevated S100A4 levels are associated with a more aggressive phenotype and a poor prognosis [11,18,26,36]. Due to its involvement in disease development and progression and its broad expression in the tumor microenvironment, S100A appears as an attractive target for cancer therapy that should allow the destruction of the tumor directly by targeting the cancer cells themselves and indirectly by destroying the supporting tumor stroma cells.…”

“…S100A4 itself has been implicated in disease development and progression, as it promotes the oncogenic phenotype of tumor cells. Its expression has been described for a variety of cancer entities, e.g., carcinoma of the breast [12,22,30,37,46,54], ovary [25], thyroid [23,36,57], esophagus [38], bladder [1,11], gallbladder [9], colon [53], colorectum [10,19], pancreas [2,40,45] and prostate [17], gastric cancers [14,26,55], lung [27,34], and brain cancers [44,52]. S100A4 expression has also been described in primary and metastatic melanoma [3,32,39].…”