The interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the lacrimal gland

泪腺多形性腺瘤及泪腺多形性腺瘤癌中的白细胞介素-6/Janus 激酶/STAT3 通路

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作者:Simon Andreasen, Steffen Heegaard, Morten Grauslund, Preben Homøe

Conclusion

The IL-6/JAK/STAT3 pathway is overexpressed in PA, and this overexpression was even more pronounced in ca-ex-PA, with a shift in the JAKs mediating STAT3 phosphorylation. Future studies are needed to clarify whether PA and ca-ex-PA could be treated with targeted therapy directed against components of the IL-6/JAK/STAT3 pathway.

Methods

Sixteen PAs and two ca-ex-PAs were examined with immunohistochemistry. Seven PAs were subjected to microdissection and subsequent qPCR.

Purpose

Pleomorphic adenoma (PA) is the most common tumour of the lacrimal gland, but very little is known about its biology. It has a tendency to recur and an ability to transform into the high-grade malignancy carcinoma ex pleomorphic adenoma (ca-ex-PA), which is also largely unexplored. In this study, we examine the expression of the interleukin-6/Janus kinase/STAT3 (IL-6/JAK/STAT3) pathway components in PA and ca-ex-PA.

Results

The IL-6/JAK/STAT3 pathway was overexpressed in PA compared to normal lacrimal gland. Overexpression of phosphorylated JAK1 (p-JAK1) and cyclin D1 was significantly overexpressed in ductal cells compared with myoepithelial cells in PA. A shift from p-JAK1 to p-JAK2 and p-Tyk2 overexpression was seen between PA and ca-ex-PA, combined with a high p-STAT3 expression in the latter.

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