Share This Article:

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

Abstract Full-Text HTML XML Download Download as PDF (Size:305KB) PP. 225-230
DOI: 10.4236/jct.2014.53029    3,029 Downloads   4,196 Views  

ABSTRACT

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.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Oualla, K. , Mellas, N. , El’mrabet, F. , Arifi, S. , Amarti, A. , Taleb, K. , Tizniti, S. and Elmesbahi, O. (2014) Primary Anorectal Melanomas Interest of Targeting C-KIT in Two Cases from a Series of 11 Patients. Journal of Cancer Therapy, 5, 225-230. doi: 10.4236/jct.2014.53029.

References

[1] Chang, A.E., Karnell, L.H. and Menck, H.R. (1998) The National Cancer Data Base Report on Cutaneous and Noncutaneous Melanoma: A Summary of 84,836 Cases from the Past Decade. Cancer, 83, 1664-1678. http://dx.doi.org/10.1002/(SICI)1097-0142(19981015)83:8<1664::AID-CN CR23>3.0.CO;2-G
[2] Balicevic, D., Tomic, K., Bekavac-Beslin 1., M., Kovacevic, I., Mijic, A., Belicza, M, et al. (2006) Synchronous Anorectal Melanoma. World Journal of Gastroenterology, 12, 3453-3455.
[3] van Schaik, P.M., Ernst, M.F., Meijer, H.A. and Bosscha, K. (2008) Melanoma of the Rectum: A Rare Entity. World Journal of Gastroenterology, 14, 1633-1635. http://dx.doi.org/10.3748/wjg.14.1633
[4] Roviello, F., Cioppa, T., Marrelli, D., Nastri, G., De Stefano, A., Hako, L. and Pinto, E. (2003) Primary Ano-Rectal Melanoma: Considerations on a Clinical Case and Review of the Literature. Chirurgia Italiana, 55, 575-580.
[5] Takahashi, T., Velasco, L., Zarate, X., Medina-Franco, H., Cortes, R., de la Garza, L. and Gamboa-Dominguez, A. (2004) Anorectal Melanoma: Report of Three Cases with Extended Follow-Up. Southern Medical Journal, 97, 311-313. http://dx.doi.org/10.1097/01.SMJ.0000091034.77040.AC
[6] Walls, E.W. (1958) Observations on the Microscopic Anatomy of the Human Anal Canal. British Journal of Surgery, 45, 504-512. http://dx.doi.org/10.1002/bjs.18004519317
[7] Fenger, C. and Lyon, H. (1982) Endocrine Cells and Melanin-Containing Cells in the Anal Canal Epithelium. The Histochemical Journal, 14, 631-639. http://dx.doi.org/10.1007/BF01011895
[8] Cagir, B., Whiteford, M.H., Topham, A., Rakinic, J. and Fry, R.D. (1999) Changing Epidemiology of Anorectal Melanoma. Diseases of the Colon & Rectum, 42, 1203-1208. http://dx.doi.org/10.1007/ BF02238576
[9] Goldman, S., Babuche, G. and Pahlman, L. (1990) Anorectal Malignant Melanoma in Sweden: Report of 49 Patients. Diseases of the Colon & Rectum, 33, 847-857. http://dx.doi.org/10.1007/BF02051925
[10] Winburn, G.B. (2001) Anal Carcinoma or “Just Hemorrhoids”? American Surgeon, 67, 1048-1058.
[11] Hillenbrand, A., Barth, T.F.E., Henne-Bruns, D. and Formentini, A. (2007) Anorectal Amelanotic Melanoma. Colorectal Disease, 10, 612-615. http://dx.doi.org/10.1111/j.1463-1318.2007.01400.x
[12] Antonescu, C.R., Busam, K.J., Francone, T.D., et al. (2007) L576P KIT Mutation in Anal Melanomas Correlates with KIT Protein Expression and Is Sensitive to Specific Kinase Inhibition. International Journal of Cancer, 121, 257-264. http://dx.doi.org/10.1002/ijc.22681
[13] Podnos, Y.D., Tsai, N.C., Smith, D. and Joshua, D.I. (2006) Factors Affecting Survival in Patients with Anal Melanoma. American Surgeon, 72, 917-920.
[14] Yeh, J.J., Shia, J., Hwu, W.J., Busam, K.J., Paty, P.B., Guillem, J.G., Coit, D.G., Wong, W.D. and Weiser, M.R. (2006) The Role of Abdominoperineal Resection as Surgical Therapy for Anorectal Melanoma. Annals of Surgery, 244, 1012-1017. http://dx.doi.org/10.1097/01.sla.0000225114.56565.f9
[15] Yap, L.B. and Neary, P. (2004) A Comparison of Wide Local Excision with Abdominoperineal Resection in Anorectal Melanoma. Melanoma Research, 14, 147-150. http://dx.doi.org/10.1097/00008390-200404000-00012
[16] Ballo, M.T., Gershenwald, J.E., Zagars, G.K., Lee, J.E., Mansfield, P.F., Strom, E.A., Bedikian, A.Y., Kim, K.B., Papadopoulos, N.E., Prieto, V.G. and Ross, M.I. (2002) Sphincter-Sparing Local Excision and Adjuvant Radiation for Anal-Rectal Melanoma. Journal of Clinical Oncology, 20, 4555-4558.
http://dx.doi.org/10.1200/JCO.2002.03.002
[17] Davies, H., Bignell, G.R., Cox, C., et al. (2002) Mutations of the BRAF Gene in Human Cancer. Nature, 417, 949-954. http://dx.doi.org/10.1038/nature00766
[18] Curtin, J.A., Busam, K., Pinkel, D. and Bastian, B.C. (2006) Somatic Activation of KIT in Distinct Subtypes of Melanoma. Journal of Clinical Oncology, 24, 4340-4346. http://dx.doi.org/10.1200/JCO. 2006.06.2984
[19] Beadling, C., Jacobson-Dunlop, E., Hodi, F.S., et al. (2008) KIT Gene Mutations and Copy Number in Melanoma Subtypes. Clinical Cancer Research, 14, 6821-6828.
[20] Demetri, G.D., von Mehren, M., Blanke, C.D., et al. (2002) Efficacy and Safety of Imatinib Mesylate in Advanced Gastrointestinal Stromal Tumors. The New England Journal of Medicine, 347, 472-480. http://dx.doi.org/10.1056/NEJMoa020461
[21] Antonescu, C.R., Busam, K.J., Francone, T.D., et al. (2007) L576P KIT Mutation in Anal Melanomas Correlates with KIT Protein Expression and Is Sensitive to Specific Kinase Inhibition. International Journal of Cancer, 121, 257-264. http://dx.doi.org/10.1002/ijc.22681
[22] Jiang, X., Zhou, J., Yuen, N.K., et al. (2008) Imatinib Targeting of KIT-Mutant Oncoprotein in Melanoma. Clinical Cancer Research, 14, 7726-7732. http://dx.doi.org/10.1158/1078-0432.CCR-08-1144
[23] Hodi, F.S., Friedlander, P., Corless, C.L., et al. (2008) Major Response to Imatinib Mesylate in KIT-Mutated Melanoma. Journal of Clinical Oncology, 26, 2046-2051. http://dx.doi.org/10.1200/JCO. 2007.14.0707
[24] Lutzky, J., Bauer, J. and Bastian, B.C. (2008) Dose-Dependent, Complete Response to Imatinib of a Metastatic Mucosal Melanoma with a K642E KIT Mutation. Pigment Cell & Melanoma Research, 21, 492-493. http://dx.doi.org/10.1111/j.1755-148X.2008.00475.x

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.