Background To retrospectively evaluate outcomes in patients with cutaneous angiosarcoma of the face/scalp treated curatively with surgery, radiation therapy (RT), or a combination of surgery and RT. Methods 70 patients with non-metastatic angiosarcoma underwent surgery, RT, or combined-modality therapy. Of these, 20 (29%) were treated with surgery alone, 27 (39%) with RT alone, and 23 (33%) with combined-modality therapy. 44 patients received chemotherapy, either neo-adjuvantly or adjuvantly or both. Results Median follow-up was 2.1 years. The overall survival (OS) rate was 43% at 5 years, and disease specific survival was 46% at 5 years. Tumor size > 5 cm and satellitosis were prognostic for inferior OS and DSS. Combined-modality therapy (vs. surgery alone or RT alone) was associated with improved OS, DSS, and local control (LC). Conclusion Primary local therapy with combined-modality therapy was associated with improved LC, OS, and DSS for patients with angiosarcoma of the face/scalp.

BRAK/CXCL14 is a CXC chemokine constitutively expressed at the mRNA level in certain normal tissues but absent from many established tumor cell lines and human cancers. Although multiple investigators cloned BRAK, little is known regarding the physiologic function of BRAK or the reason for decreased expression in cancer. To understand the possible significance associated with loss of BRAK mRNA in tumors, we examined the pattern of BRAK protein expression in normal and tumor specimens from patients with squamous cell carcinoma (SCC) of the tongue and used recombinant BRAK (rBRAK) to investigate potential biological functions. Using a peptide-specific antiserum, abundant expression of BRAK protein was found in suprabasal layers of normal tongue mucosa but consistently was absent in tongue SCC. Consistent with previous in situ mRNA studies, BRAK protein also was expressed strongly by stromal cells adjacent to tumors. In the rat corneal micropocket assay, BRAK was a potent inhibitor of in vivo angiogenesis stimulated by multiple angiogenic factors, including interleukin 8, basic fibroblast growth factor, and vascular endothelial growth factor. In vitro, rBRAK blocked endothelial cell chemotaxis at concentrations as low as 1 nmol/L, suggesting this was a major mechanism for angiogenesis inhibition. Although only low affinity receptors for BRAK could be found on endothelial cells, human immature monocyte-derived dendritic cells (iDCs) bound rBRAK with high affinity (i.e., K d , ϳ2 nmol/L). Furthermore, rBRAK was chemotactic for iDCs at concentrations ranging from 1 to 10 nmol/L. Our findings support a hypothesis that loss of BRAK expression from tumors may facilitate neovascularization and possibly contributes to immunologic escape.

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Purpose: Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, usually possesses BRAF mutation or rearranged in translation (RET)/PTC rearrangements. PTC usually possesses BRAF mutation or RET/PTC rearrangements. The mutation status of patients with recurrent PTC has never been characterized in a large population. Experimental Design: Mutation status was determined in a cohort of 54 patients with recurrent PTC and analyzed for clinicopathologic relationships. BRAF and ras mutations were determined by PCR and sequencing of genomic DNA. RET/PTC rearrangements were analyzed by reverse transcription-PCR. Results: BRAF mutation in exon 15 (V600E) was found in 42/54 (77.8%) recurrent PTC patients. The RET/PTC rearrangements were detected in 9 of 54 (16.7%) patients. In addition, 5 of 54 (9.3%) recurrent PTC patients had both a BRAF mutation and a RET/PTC rearrangement. The prevalence of tumors with dual mutations found in the recurrent population far exceeds the frequency historically reported for patients with primary PTC. Patients with dual mutations were significantly older (80% older than 45 years) than patients with a BRAF mutation alone (38% older than 45 years). Conclusions: Recurrent PTC is significantly associated with a predominant BRAF mutation. RET/PTC rearrangements, although commonly associated with primary PTCs in younger patients, are uncommonly found in recurrent PTC patients. In addition, the incidence of dual mutations was higher in patients with recurrent PTC than in those primary PTC, as reported by others.Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy accounting for 70% to 80% of thyroid cancer cases (1). In most cases, PTC has a very good prognosis, particularly in patients younger than ages 45 years at the time of diagnosis. However, roughly 5.7% of patients at 5 years and 9.4% of patients at 10 years with primary PTC will experience a recurrence of tumor (2). Recurrence typically occurs in the neck region, either in lymph nodes or in the thyroid bed, and less commonly in distance sites such as lung or bone. Patients who were older than 45 years at the time of initial diagnosis have a much worse prognosis when the cancer recurs. The 15-year mortality rate for this group is f30% for patients with local recurrence in the neck, and roughly 50% for patients with recurrence at distance sites (1,3,4).Several types of genetic alterations have been found in primary PTC, including mutations in BRAF or ras, and rearrangements of the RET or NTRK1 tyrosine kinase receptor. The incidence of BRAF mutations ranges from 29% to 83% depending on the cohort studied (5). The most common type of BRAF mutation found in primary PTC is a T to A substitution at nucleotide 1799 in exon 15, which results in conversion of a valine to glutamic acid at codon 600 (V600E) of the BRAF protein (6, 7). BRAF mutation has been associated with poor prognosis in PTC patients (8-10). The incidence of RET/PTC rearrangements in PTC ranges from 2.5% to 67.0% depending on the coh...