In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 8528-8528
Abstract:
8528 Background: Despite the poor prognosis of patients (pts) with MBM several pts have prolonged survival. We hypothesized that the heterogeneity of BrMM is determined by differences in melanoma biology and its brain microenvironment. Methods: We identified pts who have undergone craniotomy for MBMs. Evaluation entailed complete clinical information, acquisition of archived melanoma brain metastases, histopathologic analysis of hematoxylin and eosin-stained sections (n=101), whole genome expression profiling (WGEP, Illumina DASL) in 29 archived tissues. Results were validated by immunohistochemistry (IHC) or in situ hybridization (ISH). Results: In univariate analysis (log-rank) factors significantly associated with prolonged survival were high immune infiltrate (HII) plus low hemorrhage (hazard ratio, HR, 2.71, p 〈 0.001), present melanin (1.67, p=0.03), and recursive partitioning analysis (RPA) class 1 (0.37, p 〈 0.0001). No association between HII and use of immunotherapy prior to craniotomy was noted. Only RPA class 1 (p=0.029) and HII plus low hemorrhage (p=0.002) remained significant in Cox proportional hazards model analysis. Gene set analysis of WGEP data confirmed that Encarta pathways related with T-cell activation and differentiation were significantly associated with prolonged survival whereas Y branching of actin filaments, presenilin action in Notch and Wnt signaling, G-protein signaling through tubby protein, lissencephaly gene in neuronal migration and development are among the gene categories associated with worse survival. IHC and ISH analysis of tumor sections for various markers (n=40) showed that high peritumoral CD3+ (3.31, p=0.009), high peritumoral CD4+ (4.41, p=0.014), and high peritumoral CD8+ (3.02, p=0.030) are associated with prolonged survival whereas neither CD14+ nor FoxP3+ infiltrate, nor high melanoma expression of antigen presentation molecules are associated with survival. Conclusions: Our study is the first to document that high peritumoral T-cell infiltrates are associated with prolonged survival. High tumor hemorrhage, an adverse prognostic sign, reflects aggressive melanoma cells that migrate and invade in the brain.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.8528
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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