Abstract
OBJECTIVE
Recent studies have shown that Th-17 related genes are expressed in cutaneous melanomas. Gene mutations of CD117, also known as c-kit, a tyrosine kinase receptor, have also been found in cutaneous and mucosal melanomas. The objective of our study was to study the expression of Th-17-related genes and c-kit in head and neck mucosal melanomas.
METHOD
Thirty-eight paraffin-embedded mucosal melanoma sections from the nasal cavities and paranasal sinuses were analyzed. Nine cases were extracted with TRIzol after deparaffinizing with xylene and first strand cDNA synthesis was performed. PCR for hGAPDH was used as an internal control. Two rounds of nested PCR for IL17A/B/C/D/E/F, RORgammaT, FoxP3, CD27, PLZF, CD70 and CTLA-4 were performed. Twenty-nine cases were stained by automated immunohistochemistry using a pre-diluted monoclonal c-kit antibody (clone 9.7, Ventana Medical Systems, Tucson, AZ) and by a standard avidin-biotin complex utilizing the BenchMark XT system (Ventana Medical Systems, Tucson, AZ).
RESULTS
Expression of Th-17 related genes was detected. We found 2/9 cases positive for CTLA4, IL17C, IL17D, IL17E, RORgamma T and FoxP3; 4/9 for CD27 and IL17A; 6/9 for IL17B; and 1/9 for CD70. No expression was seen for PLZF and IL17F. Increased c-kit expression was identified in 25 of the 29 (86.2%) mucosal melanoma samples. Five tumors were diffusely positive (4+), 9 were positive (3+), 7 were patchy positive (2+), and 4 showed focal and weak (1+) staining.
CONCLUSION
Our results show that Th-17 related genes (CTLA4, IL17C, IL17D, IL17E, RORgamma T, FoxP3 and CD70) are expressed in mucosal melanoma. Furthermore, c-kit expression is also increased in the majority of head and neck mucosal melanoma samples from our study. These findings may help establish the role for targeted therapy such as tyrosine kinase inhibitors (Gleevec) and IL-2 in head and neck mucosal melanomas.