Physician awareness of the spectrum of secondary malignancies associated with BRAF inhibitor treatment will support their early detection and treatment.
Thirty-three samples (7 of 25 primaries, 15 of 25 regional metastases, 5 of 25 nodal metastases, and 6 of 10 distant metastases) harbored the V599EB-RAF mutation (39%), 12 contained a Q61R N-RAS mutation and 5 a Q61K N-RAS mutation.
Therefore, we established a large collection of patient-derived xenografts (PDXs), derived from BRAF(V600E), NRAS(Q61), or BRAF(WT)/NRAS(WT) melanoma metastases prior to treatment with BRAF inhibitor and after resistance had occurred.
In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%).
In this study, the occurrence and percentage of the BRAFV600E mutated allele was not preferentially associated with the development of metastases and the average mutated allele percentage decreased as the tumor progresses from the primary site to the lymph node metastatic sites.
Here we analyse 20 BRAF(V600)-mutant melanoma metastases derived from 10 patients treated with the combination of dabrafenib and trametinib for resistance mechanisms and genetic correlates of response.
The utility of immunohistochemistry (IHC) as an alternative approach for detection of BRAF(V600E) in the thoracic metastases of sporadic mCRC patients has not been evaluated until now.
Discordance in BRAF mutation status was found only in four patients, involving all three patients in whom sentinel lymph node (SLN) metastases were sampled.
Patients were matched according to somatic <i>BRAF</i>V600E mutation (80 BRAF+ and 80 BRAF- patients) and to the presence (LN+, 40 patients each group) or absence (LN, 40 patients each group) of neck lymphnode metastases.
Overall median survival time (MST), stratified for variables, including BRAFV600E mutation and eligibility for treatments with new immunotherapy drugs, was retrospectively assessed in 41 patients with pelvic melanoma loco regional metastases.
In multiple regression analyses, panitumumab treatment, liver-only metastases and WT BRAF status were consistently associated with improved ETS and DpR outcomes.
Mutations of the BRAF gene were correlated to superficial spreading melanoma (odds ratio = 1.31), localization in the torso (odds ratio = 1.42) and presence of metastases.
We therefore analyzed the correlation of BRAFV600E and ERK-activation in 20 malignant melanomas and 21 subsequently evolved, paired metastases of the same donor by BRAF exon 15 DNA sequencing and phospho-specific immunohistochemistry for ERK.
We investigate the effect of radioactive iodine (RAI) therapy on the clinical outcome in PTC patients with the BRAF(V600E) mutation without distant metastases.
Transcriptome profiling revealed that transcription factor HMGA2, previously unrecognized in melanoma pathogenesis, is significantly upregulated in primary melanoma and metastases (P-values=1.2 × 10(-7) and 9 × 10(-5)) compared with N. HMGA2 overexpression is associated with BRAF/NRAS mutations (P=0.0002).
We examined TTF1 nuclear expression in the context of adverse pathological features, disease recurrence, and BRAF status in papillary thyroid carcinomas with (n = 182) and without (n = 303) nodal metastases.
BRAFV600E gene mutation was documented in this lesion, and the patient received vemurafenib, with dramatic improvement noted on positron emission tomography scan after 2 months of treatment, soon followed by development of extensive metastases, including to brain.
Genomic DNA from a total of 749 tumor samples (451 primary tumors and 298 metastases) in 513 consecutively-collected patients with advanced melanoma (AJCC stages III and IV) was screened for mutations in exon 15 of BRAF gene and, at lower extension (354/513; 69%), in the entire coding DNA of NRAS gene by automated direct sequencing.
In the present phase II study we administered intravenously cisplatin (80 mg/mq, day 1), dacarbazine (250 mg/mq/day, days 1-3), vinblastine (2 mg maximum, day 1) every 21 days as first line treatment for patients with unresectable metastases of uveal melanoma and BRAF wild type.