High Proliferation Index Is Associated with Reduced Survival in Anorectal Melanomas – An Immunohistochemical and Molecular Study
Dov Hershkovitz, Einav Simon, Edmond Sabo, Judith Sandbank, Gabriel Groisman, Victoria Doviner, Isaac Cohen, Ofer Ben-Izhak. Rambam Health Care Campus, Haifa, Israel; Assaf Harofeh Medical Center, Zerifin, Israel; Hillel Yaffe Medical Center, Hadera, Israel; Hadassah University Hospital, Jerusalem, Israel; Western Galilee Regional Hospital, Nahariya, Israel
Background: Melanoma of the anorectum (ARMM) is a rare yet lethal malignancy. It has worse prognosis compared to cutaneous melanoma (CM), and to date, very little in known about the molecular basis of ARMM and its markers of prognosis. Interestingly, recent studies have indicated some biological and molecular differences in the pathogenesis of ARMM and CM. Understanding the pathogenetic pathways specific for ARMM might allow the development and application of targeted therapies to ARMM patients. Additionally, identification of biological markers in ARMM might also aid determining patients' prognosis.
Design: We collected clinical and prognostic data from 61 cases of ARMM. Tissue samples from these patients' tumors were analyzed using immunohistochemistry for the expression of bcl-2, p53 and Ki67. Additionally, DNA was extracted from 26 samples, which were scrutinized for oncogenic mutations in BRAF and NRAS. We then correlated the immunohistochemical and molecular results with patients' clinical data and prognosis.
Results: The median survival in the group was 13 months. Thirty eight patients (62%) were females and 23 (38%) were males. The median age at diagnosis was 66 years. In the immunohistochemical analysis 32 (52%) were positive for bcl-2, 21 (34%) were positive for p53 and the median proliferation index measured with Ki67 was 44%. The molecular analysis identified NRAS mutations in 5 (19%) of the 26 cases analyzed. No mutations were identified in BRAF. Statistical analysis demonstrated an association between disease stage and patients' survival with 16 months survival in stage II compared to 8 months survival in stage IV (p=0.025). Additionally, high proliferation index was associated with survival (19 months in ≤44% compared to 8 months in >44%, p=0.0008). No association was found between patients' prognosis and other clinical or immunohistochemical variables. The presence of NRAS mutation was not associated with altered prognosis.
Conclusions: Our results indicate that in ARMM disease stage and proliferation index might serve as markers for prognosis. Additionally, we found oncogenic NRAS mutations in 19% of the cases undergoing molecular analysis, and possibly, treatments targeting this molecular pathway might be of benefit in this subset of patients.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 101, Wednesday Morning