Multiple primary melanoma in association with other personal and familial cancers.

BACKGROUND: Multiple primary melanoma (MPM) is known to be associated with familial melanoma. However, the association between MPM and other personal and familial cancers is not well documented. The objective of this study was to evaluate the association between MPM and personal history of other cancers or cancer history among first-degree relatives (FDRs). METHODS: We performed a retrospective case-control study including cases with gender-matched MPM and single primary melanoma (SPM) at a 1:2 ratio from the University of Pittsburgh Cancer Institute Melanoma Center Biological Sample and Nevus Bank. The associations between MPM and other cancers were evaluated using univariable and multivariable logistic regression models. RESULTS: In total, 378 patients (44.2% men; median age 52 years) were enrolled, including 252 with SPM and 126 with MPM. In comparison to patients with SPM, patients with MPM were more likely to have squamous cell carcinoma (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.001-3.79, p = 0.047) and prostate cancer (OR 2.72, 95% CI 1.07-7.01, p = 0.034). FDRs of patients with MPM had higher prevalence of melanoma (OR 2.37, 95% CI 1.31-4.28, p = 0.004) and prostate cancer (OR 2.92, 95% CI 1.47-6.14, p = 0.002) but not other cancers. In multivariable analysis, the association remained significant between MPM and squamous cell carcinoma (OR 2.18, 95% CI 1.08-4.39, p = 0.028), prostate cancer (OR 2.85, 95% CI 1.09-7.54, p = 0.032), FDR history of melanoma (OR 2.37, 95% CI 1.31-4.29, p = 0.004), and FDR history of prostate cancer (OR 3.26, 95% CI 1.59-6.83, p = 0.001). CONCLUSIONS: Patients with MPM have a higher prevalence of personal and FDR histories of nonmelanoma skin cancers and prostate cancer.

Poorer survival outcomes in patients with multiple versus single primary melanoma.

BACKGROUND: Given equivocal results related to overall survival (OS) for patients with multiple primary melanomas (MPMs) compared with those with single primary melanomas (SPMs) in previous reports, the authors sought to determine whether OS differs between these 2 cohorts in their center using their UPCI-96-99 database. Secondary aims were to assess the differences in recurrence-free survival (RFS). In a subset of patients, transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) was performed to assess disease-associated genes of interest. METHODS: This retrospective case-controlled study included patients with MPMs and age-, sex-, and stage-matched controls with SPMs at a 1:1 ratio. Cox regression models were used to evaluate the effect of the presence of MPMs on death and recurrence. NanoString PanCancer Immune Profiling was used to assess peripheral blood immune status in patients. RESULTS: In total, 320 patients were evaluated. The mean patient age was 47 years; 43.8% were male. Patients with MPMs had worse RFS and OS (P = .023 and P = .0019, respectively). The presence of MPMs was associated with an increased risk of death (hazard ratio [HR], 4.52, P = .0006), and increased risk of disease recurrence (HR, 2.17; P = .004) after adjusting for age, sex, and stage. The degree of tumor-infiltrating lymphocytes (TILs) was different between the first melanoma of MPMs and SPMs. Expression of CXCL6 and FOXJ1 was increased in PBMCs isolated from patients with MPMs. CONCLUSIONS: Patients with MPMs had worse RFS and OS compared with patients with SPMs. Immunologic differences were also observed, including TIL content and expression of CXCL6/FOXJ1 in PBMCs of patients with MPMs, which warrant further investigation.