Microphthalmia transcription factor analysis in posterior uveal melanomas.
OBJECTIVE
The protein encoded by the Microphthalmia gene (MITF) is a transcription factor essential for the development and survival of melanocytes. It serves as a master regulator in modulating extracellular signals. Because of its central role in melanocytes survival and to assess its potential use as a histopathological marker for melanoma, MITF expression was examined in human choroidal melanomas.


METHODS
Fifty-seven paraffin-embedded sections of choroidal melanoma specimens and 1 choroidal melanoma cell line were analyzed using immunochemistry and RT-PCR. Normal choroids and normal choroidal melanocyte cells were used as control.


RESULTS
Sixty-five percent of the tumoral specimens stained positively for MITF with a predominant nuclear pattern of reactivity. MITF-M and MITF-A isoforms were detected by RT-PCR in all specimens examined. Using a chimeric protein resulting from the fusion of each Mitf protein with the GFP, Mitf-M exhibited an exclusive nuclear staining whereas Mitf-A exhibited a mixed nuclear and cytoplasmic staining. No correlation between MITF-positivity and parameters such as cell type, largest tumor diameter, sclera invasion, mitotic figures was observed. In contrast, a significant negative association was found between MITF staining and the pigmentation (p=0.02) and a positive correlation between MITF staining and the proliferative marker Ki67 was found (p=0.02).


CONCLUSIONS
MITF may be implicated in choroidal melanoma pigmentation and proliferation. Further analysis should provide new insights into the mechanisms underlying the molecular and cellular changes of choroidal melanomas.
Service d'ophtalmologie, Centre Hopitalier de Lens, Route de La Bassée, Lens 62307, France. fmouriaux@ch-lens.fr
Frédéric
F
Mouriaux
Sylvie
S
Vincent
Zoulika
Z
Kherrouche
Claude Alain
CA
Maurage
Nathalie
N
Planque
Didier
D
Monté
Pierre
P
Labalette
Simon
S
Saule
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002830:Choroid Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor; D008875:Middle Aged; D010858:Pigmentation; D020033:Protein Isoforms / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D015415:Biomarkers; D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D020033:Protein Isoforms; D014157:Transcription Factors