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


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


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.


CONCLUSIONS
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.
Department of Otorhinolaryngology Head & Neck Surgery and Audiology, Rigshospitalet, Copenhagen, Denmark.|Department of Otorhinolaryngology and Maxillofacial Surgery, Køge University Hospital, Køge, Denmark.|University of Copenhagen, Copenhagen, Denmark.
Simon
http://orcid.org/0000-0002-1528-4988
S
Andreasen
Department of Pathology, Rigshospitalet, Copenhagen, Denmark.|Department of Ophthalmology, Righospitalet-Glostrup, Copenhagen, Denmark.
Steffen
S
Heegaard
Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
Morten
M
Grauslund
Department of Otorhinolaryngology and Maxillofacial Surgery, Køge University Hospital, Køge, Denmark.|University of Copenhagen, Copenhagen, Denmark.
Preben
P
Homøe
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008949:Adenoma, Pleomorphic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D005134:Eye Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D007766:Lacrimal Apparatus Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053612:Janus Kinases

JAK
; Interleukin-6; STAT3; carcinoma ex pleomorphic adenoma; lacrimal gland; pleomorphic adenoma