Presence of immune cells, low tumor proliferation and wild type BRAF mutation status is associated with a favourable clinical outcome in stage III cutaneous melanoma

Abstract

BackgroundThe variable prognosis in stage III cutaneous melanoma is partially due to unknown prognostic factors. Improved prognostic tools are required to define patients with an increased risk of developing metastatic disease who might benefit from adjuvant therapies. The aim was to examine if cellular immune markers in association with tumor proliferation rate and BRAF mutation status have an impact on prognosis in stage III melanoma.MethodsWe have used two sets of case series with stage III disease: 23 patients with short survival (≤ 13 months) and 19 patients with long survival (≥ 60 months). Lymph node metastases were analyzed for Ki67, CD8 and FOXP3 protein expression using immunohistochemistry. BRAF mutation status was analyzed in a previous study on the same samples.ResultsLow tumor proliferation rate was significantly associated with a better prognosis (p = 0.013). Presence of FOXP3+ T cells was not correlated to adverse clinical outcome. A highly significant trend for a longer survival was found in the presence of an increasing number of markers; CD8+ and FOXP3+ T cells, low tumor proliferation and BRAF wildtype status (p = 0.003). Presence of at least three of these four markers was found to be an independent favorable prognostic factor (OR 19.4, 95% CI 1.9-197, p = 0.012), when adjusting for ulceration and number of lymph node metastases. Proliferation alone remained significant in multivariate analyses (OR 26.1, 95% CI 2.0-344, p = 0.013) but with a wider confidence interval. This panel still remained independent when also adjusting for a previously identified prognostic glycolytic-pigment panel.ConclusionsWe have demonstrated that presence of immune cells in association with tumor proliferation and BRAF mutation status may further contribute to identify stage III melanoma patients with high risk of relapse.

Patterns of Immune Infiltration in HNC and Their Clinical Implications: A Gene Expression-Based Study

“…Neutrophils and Macrophages M1 are related to radiation therapy. Our data further validated these findings from the previous studies that specific immune cells were related to predicting clinical outcome (35–37).…”

A novel 7 RNA-based signature for prediction of prognosis and therapeutic responses of wild-type BRAF cutaneous melanoma

“…The former up-regulated processes are involved in the enhancement of cell proliferation and are linked to malignancy of cancer [ 33 ], which means the poor survival of WT Bf-CM predicted by this signature might be resulted from the more malignant behavior in cancer biology. This was supported by a retrospective study which concluded that low tumor proliferation rate was significantly associated with a better prognosis [ 45 ]. Moreover, in spite of the removal from sub-classification of thin melanomas in recent the AJCC staging system [ 46 ], mitotic rate can still be a significant prognostic indicator especially for WT Bf-CM.…”

“…To date, immune checkpoint blockage therapy has been recommended for the treatment of advanced WT Bf-CM [ 47 ]. Additionally, the infiltration of immune cells can both serve as the predictor of responses to checkpoint therapy and WT Bf-CM survival [ 45 , 48 , 49 ]. However, little differences in immune infiltration was observed in the WT Bf-CM patients between high- and low- risk groups.…”

A Novel 7 RNA-Based Signature for Prediction of Prognosis and Therapeutic Responses of Wild-Type BRAF Cutaneous Melanoma

“…The former up-regulated processes are involved in the enhancement of cell proliferation and are linked to malignancy of cancer 32 , which means the poor survival of WT Bf-CM predicted by this signature might be resulted from the more malignant behavior in cancer biology. This was supported by a retrospective study which concluded that low tumor proliferation rate was signi cantly associated with a better prognosis 44 . Moreover, in spite of the removal from sub-classi cation of thin melanomas in recent the AJCC staging system 45 , mitotic rate can still be a signi cant prognostic indicator especially for WT Bf-CM.…”

“…To date, immune checkpoint blockage therapy has been recommended for the treatment of advanced WT Bf-CM 46 . Additionally, the in ltration of immune cells can both serve as the predictor of responses to checkpoint therapy and WT Bf-CM survival 44,47,48 . However, little differences in immune in ltration was observed in the WT Bf-CM patients between high-and low-risk groups.…”