Abstract

Abstract The incidence of malignant melanoma is increasing worldwide. Melanomas are most commonly localized in the skin but can arise anywhere in the body where melanocytes exist. Gastrointestinal melanoma (GM) is a rare form of this disease. The prognosis of GM is poor compared to that of skin melanoma (SM), however GM has not been well characterized. GM is difficult to diagnose at an early stage because of the anatomical location. Furthermore, it is usually challenging for pathologists to diagnose GM, especially given the small amount of biopsy samples usually collected. In the present study, we examined the differences between GM and SM. Design: The clinicopathological characteristics, morphological feature, mitosis rate, expression of melanoma stem cell markers (nestin, SOX2, and ABCB5), and presence of the BRAFV600E mutation were evaluated for 10 cases of GM and 31 of SM. Results: Patients with GM tended to be older than those with SM. Moreover, GMs were more likely to be amelanotic (50% vs. 7%, P=0.001) and to display round cells (70% vs. 23%, P=0.02) than were SMs, and the mitosis rate was higher in GMs than in SMs (P<0.05). The incidence of lymph-node metastasis (60% vs. 32%, P<0.05) and distant metastasis (10% vs. 6.5%, P=0.02) was higher in GMs than in SMs at the point of resection. Expression of stem cell markers did not differ between groups; however, in SM, advanced-stage disease was associated with higher expression of nestin than was early-stage disease (P<0.05). Immunohistochemically, the expression of BRAFV600E was lower in GMs than in SMs (1.0 vs 3.3, P=0.01). Conclusion: Our investigation revealed that, compared to SM patients, GMs were generally older, more likely to display round cells, and be amelanotic. Moreover, they had a lower frequency of BRAFV600E mutations than did SM patients. We believe that identification of these features may aid in the diagnosis of GM and SM and contribute to new targeted therapies for GM. Clinicopathological characteristics of melanomas of the skin and gastrointestinal tractSkinGastrointestinal tractN3110Age66.7 ± 16.875.7 ± 14.9Cell morphologySpidle24 (77.4%)3 (30.0%)Round7 (22.6%)7 (70.0%)MelaninNegative2 (6.5%)5 (50.0%)Positive29 (93.5%)5 (50.0%)Cell proliferation markersMIB-1 index25.6 ± 19.135.0 ± 18.1Stage I,II22.2 ±17.221.7 ±10.4Stage III,IV30.8 ±21.540.7 ±18.1Total mitosis14.5 ± 22.735.8 ± 30.7 *Stage I,II8.6 ± 12.83.8 ± 3.5Stage III,IV23.8 ± 31.349.4 ± 26.2**Immunohistochemical scoreNestin7.6±3.96.7±2.8Stage I,II6.3±3.95.7±2.5Stage III,IV9.6±2.9 **7.1±3.0BRAF3.3±3.31.0±1.5*Stage I,II2.9±3.21.0±1.0Stage III,IV4.1±3.31.0±1.2*P<0.05 vs skin melanoma. **P<0.05 vs stage I, II by student-t test. Citation Format: Michiko Akiyama, Yoko Matsuda, Tomio Arai, Hidehisa Saeki. Aggressive features of gastrointestinal melanoma as compared to skin melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2010.

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