MUC1 Expression in Papillary Thyroid Carcinoma Is Associated with BRAF Mutation and Lymph Node Metastasis;the Latter is the Most Important Risk Factor of Relapse

Abstract

Background:

The incidence of papillary thyroid carcinoma (PTC) has increased over the past 30 years in Western countries. PTC is usually associated with a good prognosis, but there is a wide range of aggressiveness, and some patients develop distant metastasis and/or resistance to standard treatment. Early identification of these high-risk tumors is a current challenge for appropriate patient management. MUC1 expression has been studied previously in thyroid cancer, but its prognostic value remains controversial. Here, we correlated MUC1 expression in PTC with clinical and pathological features and with the presence of the BRAF ^V600E mutation.

Methods:

We performed a clinical and morphological analysis of 190 thyroid tumors (95 PTCs and 95 adenomas). MUC1 immunohistochemistry was carried out on a tissue microarray using different antibodies. The presence of the BRAF ^V600E mutation was investigated by pyrosequencing. MUC1 mRNA levels were assessed by quantitative reverse transcription polymerase chain reaction on a subset of PTC.

Results:

MUC1 expression was observed in 49% of PTCs and was found to correlate with the presence of papillary architecture, a stromal lymphoid infiltrate, aggressive histological subtypes, extrathyroidal extension, lymph node metastasis, nuclear pseudoinclusions, lymphovascular invasion, and the presence of the BRAF ^V600E mutation (p<0.0001). MUC1 was abundant in nuclear pseudoinclusions. Multivariate analysis showed a strong association of MUC1 expression with the presence of the BRAF ^V600E mutation and lymph node metastasis (p<0.0001). Lymph node metastasis was the most important risk factor of relapse.

Conclusions:

Our study shows an association between MUC1 expression and the presence of the BRAF ^V600E mutation in PTC. Analysis of MUC1 expression could improve the risk stratification of PTCs.