Primary Anorectal Melanomas Interest of Targeting C-KIT in Two Cases from a Series of 11 Patients

摘要

Background: The anorectal location of melanomas is extremely rare (1% - 3% of all melanomas), and the prognosis remains poor because of the aggressiveness and the high metastatic potential of those tumors. The discovery that the KIT oncogene may be aberrantly activated in a subset of patients with anorectal melanoma creates a realm of possibility for the development of targeted molecular therapy. Aim: to show the epidemiologic, clinico-radiological, histological features and treatment management especially in patients with over-expression of C-KIT treated by Imatinib. Methods: It is a retrospective study conducted in the department of medical oncology at Hassan II University Hospital between January 2007 and January 2012, including all patients with histologically proven melanoma of the anorectal area. Results: 11 cases were collected, with slight female predominance. Nine patients were metastatic at the moment of diagnosis, and only two with local stage, but evolution was marked by local and distant recurrence less than 12 months after abdo-minoperineal resection. First line of chemotherapy was based mainly on paclitaxel, carboplatine and dacarbazine. Response was modest with only 3 partial responses, 4 patients with disease stability, and 4 patients with disease progression. Two patients, with over expression of C-KIT, received Imatinib as second line of treatment with significant improvement of symptoms and radiological response reaching 50%. Seven patients died with a median survival of 11 months from diagnosis to the date of death. Conclusion: Primary anorectal melanomas are very rare, with high aggressiveness and poor prognosis. Treatment management is still a big challenge given to the modest efficacy of conventional chemotherapy. Better understanding of carcinogenesis and signaling pathways will allow development of new targeted therapies.