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Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations


Schoenewolf, N L; Bull, C; Belloni, B; Holzmann, D; Tonolla, S; Lang, R; Mihic-Probst, D; Andres, C; Dummer, R (2012). Sinonasal, genital and acrolentiginous melanomas show distinct characteristics of KIT expression and mutations. European Journal of Cancer, 48(12):1842-1852.

Abstract

KIT aberrations predict the outcome of targeted therapies in acrolentiginous (ALM) and mucosal (MM) melanoma patients. KIT immunoreactivity and mutation status was assessed in 41 ALM and 25 MM patients. Of these, 19 ALM and 15 MM patients had matched primary and metastatic lesions. P-ERK was investigated in a subset of 9 ALM and 7 MM matched primary/metastatic pairs by immunohistochemistry. Heterogeneous KIT immunoreactivity was observed in both primary and metastatic lesions. Mutations were present in four of 41 ALM (10%) and five of 25 MM (20%) patients. Only vulvar mucosal samples carried KIT mutations in contrast to sinonasal lesions (p=0.0109). In KIT-mutated tumours, the mutations were present in KIT expressing as well as KIT negative cells, as shown by Laser Capture Microdissection (LCM). P-ERK expression was preferentially found in metastases. KIT mutations predict treatment outcome with KIT inhibitors. Therefore, especially vulvar melanoma patients should be screened for activating KIT mutations.

Abstract

KIT aberrations predict the outcome of targeted therapies in acrolentiginous (ALM) and mucosal (MM) melanoma patients. KIT immunoreactivity and mutation status was assessed in 41 ALM and 25 MM patients. Of these, 19 ALM and 15 MM patients had matched primary and metastatic lesions. P-ERK was investigated in a subset of 9 ALM and 7 MM matched primary/metastatic pairs by immunohistochemistry. Heterogeneous KIT immunoreactivity was observed in both primary and metastatic lesions. Mutations were present in four of 41 ALM (10%) and five of 25 MM (20%) patients. Only vulvar mucosal samples carried KIT mutations in contrast to sinonasal lesions (p=0.0109). In KIT-mutated tumours, the mutations were present in KIT expressing as well as KIT negative cells, as shown by Laser Capture Microdissection (LCM). P-ERK expression was preferentially found in metastases. KIT mutations predict treatment outcome with KIT inhibitors. Therefore, especially vulvar melanoma patients should be screened for activating KIT mutations.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Otorhinolaryngology
04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:19 Apr 2012 08:08
Last Modified:05 Apr 2016 15:46
Publisher:Elsevier
ISSN:0959-8049
Publisher DOI:https://doi.org/10.1016/j.ejca.2012.02.049
PubMed ID:22464346

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