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Melanoma

P41: Whole Transcriptome Profiling of Patients with In Transit Melanoma

Introduction: In transit melanoma (ITM) is a type of locoregional melanoma with heterogeneous presentation, disease progression, and outcomes. Herein, we aimed to profile gene expression among patients with ITM and identify those associated with favorable overall survival (OS).

Methods: Our institutional registry was queried for patients with ITM diagnosed from 1990-2020. Patients with at least one tissue block available were included in a tissue microarray (TMA). Each sample was a unique region of interest. The TMA underwent Nanostring GeoMx whole transcriptome analysis. Differential gene expression and Gene Set Enrichment was compared among patient groups by OS (< 3 years vs > 3 years), as well as those with acral and non-acral melanoma.

Results: Altogether, 184 patients with ITM were identified; 111 patients had available tissue; and 66 patients’ samples in the TMA met quality control standards for analysis. Median age at diagnosis was 61 years (IQR 52, 71) and 44% were female. Median Breslow depth of the primary tumor was 2.5 mm (IQR 2.0, 4.0) and 36% were ulcerated. Nearly 30% of patients had a positive sentinel lymph node, while 44% ultimately developed nodal disease. Median time to ITM was 17 months (IQR 10.5, 29.8). Median follow-up from ITM diagnosis was 3.7 years (IQR 2.0, 7.0) and median survival was 5.7 years (95% CI 3.7-10.2). In the TMA, there were 128 total samples across the 66 unique patients: 87 ITM, 31 lymph nodes, 9 distant metastases, and 1 primary tumor. Among all 66 patients, the hallmark gene sets comprising immune pathways, including interferon-gamma signaling, were suppressed in patients with OS < 3 years compared to > 3 years.  By grouping patients by acral melanoma status, we found that TGF-beta and DNA repair pathways were down regulated in patients with acral compared to non-acral patients. Several individual genes were also differentially upregulated in acral compared to non-acral patients.

Conclusions:

Whole transcriptome analysis of patients with ITM reveals that enrichment of immunologic pathways is associated with favorable survival. Further work is needed to elucidate differences in acral patients who develop ITM.

Learning Objectives:

  • Upon completion, participant will be able to describe in transit melanoma
  • Upon completion, participant will recognize the heterogeneity of presentation and outcomes for patients with in transit melanoma
  • Upon completion participant will be able to recognize genomic signatures associated with better prognosis for in transit melanoma