ABSTRACT
Gastrointestinal melanoma (GM) is a rare but aggressive type of malignant melanoma arising in the gastrointestinal tract. An anti-programmed cell death protein 1 (PD-1) antibody markedly improves prognosis in patients with melanoma. However, little is known regarding the expression of immune-oncology biomarkers in GM compared with skin melanoma (SM), especially in the Asian population. the present study examined clinicopathological characteristics, PD-L1 and HLA expression, and immune-oncology marker expression in 10 cases of GM and 31 cases of SM. Patients with GM exhibited significantly higher incidences of lymph node and distant metastases than patients with SM (P=0.0448 and P=0.0247, respectively). The infiltration of CD8+ lymphocytes was significantly higher in GM than in SM (P=0.0231). The infiltration of PD-1+ lymphocytes was higher in GM than in SM, but the difference was not significant (P=0.0975). PD-L1-positive melanoma exhibited a higher proportion of BRAFV600E-positive melanoma than PD-L1-negative melanoma (P=0.0317; 39.4 and 0%, respectively). PD-L1-positive melanoma exhibited significantly higher rates of CD8+ and FOXp3+ lymphocyte infiltration than PD-L1-negative melanoma (P=0.0221 and P=0.0463, respectively). By contrast, PD-1+ lymphocytes did not differ between PD-L1-positive and -negative cases. Furthermore, HLA-positive melanoma exhibited higher proportions of PD-1 (P=0.0101; 53.7 and 15.4%) and CD8 than HLA-negative melanoma (P=0.0818; 66.7 and 38.2%). These results provided useful information regarding tumor immunity in GM and SM and may contribute to the development of treatment strategies for GM.
ABSTRACT
The present study examined the differences between gastrointestinal melanoma (GM) and skin melanoma (SM). The clinicopathological characteristics, the expression of melanoma stem cell markers nestin, sex determining region Y-box 2 and ATP-binding cassette sub-family B member 5, and the presence of the BRAFV600E mutation were evaluated in 10 cases of GM and 31 cases of SM. Patients with GM had an increased mean age compared with those with SM (76 vs. 68 years). In addition, GMs were significantly more likely than SMs to be amelanotic (50 vs. 7%; P=0.001) and display round cells (70 vs. 23%; P=0.02). The mitosis rate was also significantly higher in GM compared with SM (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 significantly higher in GMs compared with SMs. The expression of stem cell markers did not differ significantly between groups, however, in the SM group advanced-stage disease was associated with a significantly higher expression of nestin than early-stage disease (P<0.05). Immunohistochemically, the expression of BRAFV600E was significantly lower in GMs compared with in SMs (1.0 vs. 3.3; P=0.01). These findings indicate that the identification of these features may aid in the diagnosis of GM and SM, as well as contribute to the development of novel targeted therapies against GM.
Subject(s)
Cell Proliferation , Intermediate Filament Proteins/antagonists & inhibitors , Melanoma/pathology , Neoplastic Stem Cells/pathology , Nerve Tissue Proteins/antagonists & inhibitors , Skin Neoplasms/pathology , Actins/metabolism , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Humans , In Vitro Techniques , Intermediate Filament Proteins/genetics , Intermediate Filament Proteins/metabolism , Melanoma/metabolism , Mice , Mice, Nude , Mitogen-Activated Protein Kinase Kinases/metabolism , Neoplasm Invasiveness/pathology , Neoplasm Invasiveness/prevention & control , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nestin , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Skin Neoplasms/metabolism , Transfection , Transplantation, HeterologousABSTRACT
Nestin, a class VI intermediate filament protein, was originally described as a neural stem cell/progenitor cell marker. Expression of nestin has been reported to be associated with the migration and metastasis of various types of tumor. In the present study, we examined the expression of nestin in malignant melanomas and nevi. Immunohistochemically, nestin was detected in all compound nevi, but not in the majority of junctional nevi. Nestin was expressed at particularly high levels in nevi with neurotization. In melanoma, nestin was expressed in all T3 and T4 cases, but only in half of the cases of T2 or less severe disease. These results indicate that the expression levels of nestin in melanoma are associated with advanced disease. In conclusion, nestin was expressed in advanced melanoma tissues and neurotized nevi. Nestin may be an important marker of melanocytic neoplasms. Further studies are required to elucidate the regulatory mechanisms of nestin expression and to examine the possibility of nestin-targeted therapy for malignant melanomas.
Subject(s)
Intermediate Filament Proteins/genetics , Melanoma/genetics , Nerve Tissue Proteins/genetics , Nevus/genetics , Skin Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Cell Line, Tumor , Cell Movement/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Melanoma/pathology , Middle Aged , Molecular Targeted Therapy , Neoplasm Staging , Nestin , Neural Stem Cells , Nevus/pathology , Skin Neoplasms/pathologyABSTRACT
Image fusion software can derive a fusion image from single photon emission computed tomography and computed tomography scans. We applied a three-dimensional fusion image to detect sentinel lymph nodes (SLNs) in 3 patients with malignant melanomas of the lumbar, vulvar and head region, respectively. During each operation, we detected SLNs at the expected site, as indicated by the fusion images. The three-dimensional image fusion could thus be confirmed as a simple and helpful method for precisely localizing SLNs in these patients.
