KIT, EGF-Receptor and HER2/Neu Expression in Malignant Melanomas of the Sinonasal Mucosa. Clues to a Specific Carcinogenic Pathway Different from Cutaneous Melanoma
R Barnoud, PP Bringuier, AB Salin, M Devouassoux-Shisheboran. Hopsices Civils de Lyon, Lyon, France
Background: KIT (CD117), EGFR (Epidermal Growth Factor Receptor) and HER2/neu, are trans-membrane receptor tyrosine kinases which are amplified and/or overexpressed in a variety of human neoplasms, including a subset of cutaneous melanomas. However, KIT expression in sinonasal melanomas, a rare site for that tumor, has been seldom studied. Moreover, EGFR and HER2/neu expression are totally unknown in these tumors.
Design: KIT, EGFR (Epidermal Growth Factor Receptor) and HER2/neu expression were studied in 18 cases, using immunohistochemistry. The grading of the immunostaining was performed on a sliding scale of 1+ to 3+ according to the percentage of reactive cells (0 = 0-5%; 1+= 6%-40%, 2+= 41%-70%; 3+ =71-100%). In addition, c-kit mutation analysis was performed in one of these cases.
Results: KIT overexpression was observed in 15 of the 18 cases (83 %). Immunohistochemistry for CD117 was weakly positive (1+) in one case (6%), moderately positive (2+) in 7 cases (47%), strongly positive (3+) in 7 cases (47%). CD117 immunoexpression persisted in the invasive component. The case tested for mutational analysis was positive for c-kit mutation within exon 17. Interestingly, only one (6%) of the 17 cases show a weak (1+) EGFR immunoreactivity which is in contrast to what is reported for cutaneous and uveal melanomas. No HER2/neu expression could be seen.
Conclusions: Our data indicate that sinonasal melanomas follow a specific carcinogenic pathway characterized by a lack of EGFR expression and a frequent and high level of KIT expression. That latter molecule can even carry activating mutation. Evaluation of the relevance of c-kit as molecular target in sinonasal melanoma warrants further investigation.
Category: Head & Neck
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 162, Wednesday Morning