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KIT genetic alterations in anorectal melanomas
  1. Raffaella Santi1,
  2. Lisa Simi2,
  3. Rossella Fucci2,
  4. Milena Paglierani1,
  5. Monica Pepi1,
  6. Pamela Pinzani2,
  7. Barbara Merelli3,
  8. Marco Santucci1,
  9. Gerardo Botti4,
  10. Carmelo Urso5,
  11. Daniela Massi1
  1. 1Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
  2. 2Clinical Biochemistry Unit, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
  3. 3Department of Oncology and Haematology, Papa Giovanni XXIII Hospital, Bergamo, Italy
  4. 4Department of Pathology, National Cancer Institute “Fondazione G. Pascale”, Naples, Italy
  5. 5Dermatopathology Section, S.M. Annunziata Hospital, ASL 10, Florence, Italy
  1. Correspondence to Raffaella Santi, Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Largo Brambilla, 3, Florence I-50134, Italy; raffaella.santi{at}


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.

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