[Show abstract][Hide abstract] ABSTRACT: Purpose:
To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients.
Frequencies of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), serum lactate dehydrogenase (LDH), routine blood counts, and clinical characteristics were assessed in 209 patients. Endpoints were overall survival (OS) and best overall response. Statistical calculations were done by Kaplan-Meier- and Cox-regression-analysis including calibration and discrimination by C-statistics.
Low baseline LDH, absolute monocyte counts (AMC), Lin-CD14+HLA-DR-/low-MDSC frequencies, and high absolute eosinophil counts (AEC), relative lymphocyte counts (RLC), and CD4+CD25+FoxP3+-Treg frequencies were significantly associated with better survival, and were considered in a combination model. 43.5% of patients presenting with the best biomarker signature had a 30% response rate and median survival of 16 months. In contrast, patients with the worst biomarkers (27.5%) had only a 3% response rate and median survival of 4 months. The occurrence of adverse events correlated with neither baseline biomarker signatures nor the clinical benefit of ipilimumab. In another model, limited to the routine parameters LDH, AMC, AEC, and RLC, the number of favorable factors (4 vs. 3 vs. 2-0) was also associated with OS (p<0.001 for all pairwise comparisons) in the main study and additionally in an independent validation cohort.
A baseline signature of low LDH, AMC and MDSCs as well as high AEC, Tregs and RLC is associated with favorable outcome following ipilimumab. Prospective investigation of the predictive impact of these markers following ipilimumab and other treatments, e.g. PD-1 antibodies, is warranted.
No preview · Article · Jan 2016 · Clinical Cancer Research
[Show abstract][Hide abstract] ABSTRACT: Melanomas associated with blue nevi (MABN) or mimicking cellular blue nevi (MMCBN) represent exceptional variants of malignant cutaneous melanocytic tumors. Uveal and leptomeningeal melanomas frequently have somatic mutations of GNAQ or GNA11, which are believed to be early driver mutations. In uveal melanomas, monosomy 3, linked to the BAP1 gene, is an adverse prognostic factor. We have studied the clinical, histologic, BAP1 expression profile, and molecular data of 11 cases of MABN/MMCBN and 24 cellular blue nevi. Most of the cases of MABN/MMCBN occurred on the scalps of adult patients and presented as rapidly growing nodules, typically >1 cm, often arising at the site of a preexisting melanocytic lesion. The MABN/MMCBN were composed of dense nests of large dermal atypical melanocytes, in some cases lying adjacent to a blue nevus. Four patients developed metastatic disease, and 2 died from their disease. A GNA11 mutation was found in 8/11 cases and a GNAQ mutation in 1 case. Seven of 11 cases showed loss of nuclear BAP1 immunohistochemical (IHC) expression in the malignant component, sparing the adjacent nevus. Array comparative genomic hybridization revealed recurrent deletions of chromosomes 1p, 3p, 4q, 6q, 8p, 16q, and 17q and recurrent gains of chromosomes 6p, 8q, and 21q. The 24 cases of cellular blue nevi frequently occurred on the sacrum, had GNAQ mutations, and showed normal positive IHC staining for BAP1. These results underscore overlapping features in all blue-like malignant melanocytic tumors. Loss of BAP1 IHC expression was restricted to melanomas, including all metastatic cases.
No preview · Article · Dec 2015 · The American journal of surgical pathology
[Show abstract][Hide abstract] ABSTRACT: Background:
Acne is a concern in adults, especially in women. The specifications in current acne grading systems are not applicable to this particular population.
To develop and validate a measurement tool (AFAST: adult female acne scoring tool) for acne in women by taking into account the specific locations of adult female acne, and to evaluate the impact of the photographic modalities on rating reproducibility.
Six experts in dermatology rated pictures of 54 women with a phototype from I to IV during two sessions, with an interval of 24 h. They rated the acne severity on the face using the GEA scale (Score 1) together with a new scale to assess acne on the mandibular zone (Score 2). Pictures of 30 women were taken using a standardized photographic device; pictures of the other 24 women were taken by their own dermatologists during daily practice.
At session 1, the inter-rater's reproducibility was good for Score 1 with an ICC of 0.77 [0.72-0.83], and excellent for Score 2 with an ICC of 0.87 [0.82-0.91]. Between sessions 1 and 2, the mean intra-rater's reproducibility was excellent for both scores with an ICC of 0.88 [0.84-0.92] for Score 1, and an ICC of 0.87 [0.78-0.92] for Score 2. Photographic modalities had no significant effect on the inter- and intra-rater's reproducibility.
For the first time, it has been demonstrated that AFAST can accurately rate acne severity in women. It is a promising, easy-to-use tool for both daily practice and clinical investigation.
No preview · Article · Dec 2015 · Journal of the European Academy of Dermatology and Venereology