KIT genetic alterations in anorectal melanomas
| Autor: | Carmelo Urso, Monica Pepi, Barbara Merelli, Daniela Massi, Rossella Fucci, Pamela Pinzani, Raffaella Santi, Lisa Simi, Milena Paglierani, Gerardo Botti, Marco Santucci |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Skin Neoplasms Kit gene Population DNA Mutational Analysis Pathology and Forensic Medicine Exon Predictive Value of Tests Biomarkers Tumor Medicine Mutational status Humans Intestinal Mucosa education Melanoma In Situ Hybridization Fluorescence Aged Retrospective Studies Aged 80 and over education.field_of_study Direct sequencing business.industry Rectal Neoplasms melanoma C-KIT mucosal melanoma General Medicine Middle Aged medicine.disease Anus Neoplasms Immunohistochemistry Proto-Oncogene Proteins c-kit Italy Mutation Female business Immunostaining |
| Popis: | Background Mucosal melanomas (MM) represent a heterogeneous tumour population that exhibits site-specific molecular profiles. Aims In a multicentre retrospective study, we investigated KIT aberrations in primary anorectal (AR) melanomas compared with melanoma metastatic to the gastrointestinal (GI) tract. Methods Primary AR MM (n=31) and GI metastatic melanoma (n=27) were studied for KIT mutations on exons 11, 13, 17 and 18 by high-resolution melting analysis, direct sequencing and c-KIT expression by immunohistochemistry. Selected cases were also investigated for increased KIT gene copy number by fluorescent in situ hybridisation. Results Functional KIT mutations were demonstrated in 11/31 (35.5%) of AR melanomas and in 1/26 (3.8%) of GI melanoma metastases (p=0.004). A significant difference emerged between primary and metastatic MM with regards to KIT-positive immunostaining (p=0.002). Immunohistochemical c- KIT protein overexpression did not correlate with KIT mutational status. Increased KIT copy number was demonstrated in 5/20 AR primary cases. Conclusions The rate of functional mutations in KIT is significantly higher in AR MM than in GI metastatic melanoma. KIT protein overexpression does not correlate with KIT mutations and cannot be used for screening purposes. Recognising the molecular heterogeneity of MM helps to identify patients who require a different therapeutic approach. |
| Databáze: | OpenAIRE |
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