Correlation of immunohistochemical markers and BRAF mutation status with histological variants of papillary thyroid carcinoma in the Korean population

Abstract

Several pathologic characteristics are associated with an adverse clinical outcome in papillary thyroid carcinoma (PTC), including the histological variant. This study aimed to investigate immunohistochemical expression and BRAF mutation status based on the histological variant and evaluated potential markers of aggressive behavior of PTC in Korean patients. In all, 407 PTC cases were classified to each histological variant, and the 94 representative cases were subjected to immunohistochemistry and BRAF mutation analysis. The classic type, follicular variant (FV) and tall cell variant (TCV) represented 76.9%, 14.2% and 6%, respectively. TCV showed a larger tumor size (P = 0.009), frequent extrathyroidal extension (P = 0.022) and cervical lymph node (LN) metastasis (P = 0.018). TCV and FV showed the reduced expression of galectin-3 (P = 0.003) and HBME1 (P = 0.114). Regardless of histology, PTEN loss and diffuse S100A4 expression were associated with LN metastasis (P = 0.007, P = 0.013). All TCVs harbored BRAF V600E mutation, and FV harbored less BRAF V600E mutation (P = 0.043). Immunohistochemical evaluation showed characteristic patterns in histological variants. PTEN and S100A4 expression are suggested as indicators of regional lymph node metastasis.

Keywords: Histological Variant; Immunohistochemistry; PTEN; S100A4; Thyroid Carcinoma, Papillary.

Fig. 1

Immunohistochemical expression of galectin-3, HBME1, and CK19 in three PTC histological variants. Galectin-3 and HBME1 expression was relatively decreased in both FV and TCV (upper and middle row, ×400), while CK19 expression was decreased only in FV (lower row, ×400). FV, follicular variant; TCV, tall cell variant.

Fig. 2

VEGF, EGFR, c-erbB2, and β-catenin expression in three PTC histological variants. VEGF expression was frequently increased in TCV (score ≥ 1, P = 0.012, first row, ×400) while no EGFR expression was detected in most FV and TCV cases (P = 0.002, second row, ×400). TCV showed reduced c-erbB2 positivity (score = 0, third row, ×400) and the characteristic paranuclear dot-like β-catenin positivity (fourth rows). FV, follicular variant; TCV, tall cell variant.

Fig. 3

PTEN and S100A4 expression in PTC. PTEN expression was detected mainly in the cytoplasm of tumor cells (A, score = 2; B, score = 1, ×400) compared to the case with PTEN loss (C, score = 0). S1004 was expressed in both the nucleus and cytoplasm (D, score = 2; E, score = 1; F, score = 0, ×400).