KIT genetic alterations in anorectal melanomas.
BACKGROUND
Mucosal melanomas (MM) represent a heterogeneous tumour population that exhibits site-specific molecular profiles.


OBJECTIVE
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.
Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
Raffaella
R
Santi
Clinical Biochemistry Unit, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
Lisa
L
Simi
Clinical Biochemistry Unit, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
Rossella
R
Fucci
Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
Milena
M
Paglierani
Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
Monica
M
Pepi
Clinical Biochemistry Unit, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
Pamela
P
Pinzani
Department of Oncology and Haematology, Papa Giovanni XXIII Hospital, Bergamo, Italy.
Barbara
B
Merelli
Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
Marco
M
Santucci
Department of Pathology, National Cancer Institute "Fondazione G. Pascale", Naples, Italy.
Gerardo
G
Botti
Dermatopathology Section, S.M. Annunziata Hospital, ASL 10, Florence, Italy.
Carmelo
C
Urso
Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
Daniela
D
Massi
D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology; D007558:Italy; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics*; D012004:Rectal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit