The clinical significance of c-Kit mutations in metastatic oral mucosal melanoma in China

Abstract

c-Kit mutations are frequently detected in mucosal melanomas, but their clinical significance in metastatic oral mucosal melanomas (OMM) remains unclear. The main purpose of this study was to investigate the clinical and pathological features of metastatic OMMs with c-Kit mutations and the efficiency of the tyrosine kinase inhibitor imatinib in treating metastatic OMMs. We found thatresidual primary lesion and neck lymph nodes could act as independent prognostic factors in metastatic OMM patients. c-Kit mutations were detected in 22 out of 139 (15.8%) metastatic OMM patients. Under chemotherapy, the overall survival (OS) of c-Kit mutant patients was significantly shorter than that of wild-type patients. The Ki67 expression was significantly higher in c-Kit mutant patients than in wild-type patients. In distant metastatic OMM patients with c-Kit mutations, the treatment with c-Kit inhibitor resulted in a better OS. In conclusion, residual primary lesion, cervical lymph nodes and c-Kit mutations act as adverse prognostic factors of metastatic OMMs. The Kit inhibitor imatinib could benefit metastatic OMM patients with c-Kit mutations.

CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway

“…The 4.2% prevalence of KIT mutations in our samples agrees with the minimum value of the range of frequencies previously reported in SNM (4% to 12.5%) but is inferior to the 15% and 27% reported in OM and the 25.9% of other POSNM series . An intriguing finding of this series is the low frequency of KIT mutations (4.2%), despite simultaneously high C‐KIT protein expression.…”

“…Elevated C‐KIT expression (85%) was observed, despite the low incidence of KIT mutations (3.2%), and this phenomenon has been reported in other POSNM series . Protein expression is related to the initial stages of tumour progression, but it has also been observed in the invasive component of KIT mutated tumours upon relapse and in metastatic lesions, correlating the presence of mutation and over‐expression with a high recurrence rate and poor overall survival; so it has been proposed that KIT may have an opposing role in the pathogenesis of melanoma . Although considering that almost all of our samples were invasive neoplasms, we are unable to either confirm the last finding or to correlate immunohistochemistry results with morbidity or survival status.…”

“…The anatomical site of the tumour could partially explain the different frequencies of KIT mutations between mucosal melanomas since higher rates among vulvovaginal cases have been reported compared to POSNM cases . This might be linked with the potential of neural crest cells to differentiate in melanocytes or could also be associated with ethnic origins, as it is found at a higher frequency in mucosal melanomas among Asiatic compared to Caucasian patients …”

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

“…The incidence of melanoma has been rising faster than any other solid tumour . In China, 20,000 new cases of melanoma are diagnosed each year . Malignant melanoma is characterized by high metastatic potential, high resistance to chemotherapy and a poor survival rate.…”

“…In recent years, researchers have made great endeavour to evaluate several chemo‐ and immune‐based therapies for melanoma treatment in clinical trials. However, it is disappointing that most of those therapies had no significant benefits in melanoma patients . Recently, the efficacy of BRAF inhibition and immune checkpoint blockade approaches has been shown in melanoma patients .…”