Angiosarcoma Of The Scalp And Face:Clinical And Molecular Insights

BackgroundAngiosarcoma is a rare soft tissue neoplasm of high malignancy and dismal outcome.The skin of the scalp and face in elderly patients is the most common primary site.Searching for new molecular biomarkers is of great importance for unveiling its mechanism and investigating new therapy.The mammalian target of rapamycin(mTOR)plays a major role in the regulation of protein synthesis,cell growth,proliferation,survival and angiogenesis.Alterations of the mTOR signaling pathway are implicated in a range of human cancers,and thus mTOR is being actively pursued as a therapeutic target.In recent years,in vitro and animal experiments revealed that deregulation of mTOR signaling pathway was common in angiosarcoma.However,there have been limited studies on the expression of mTOR signaling pathway in human angiosarcoma,especially the cutaneous angiosarcoma of the scalp and face.Objective1.To assess outcomes of patients with angiosarcoma of the scalp or face,as well as to identify factors associated with prognosis.2.To investigate the activation of mTOR signaling pathway in cutaneous angiosarcoma of the scalp and face,and to evaluate its correlation with outcomes.Methods1.Retrospective study of 23 patients diagnosed with cutaneous angiosarcoma localised to the face and scalp between January 1,2010 and December 31,2016 at Peking Union Medical College Hospital.Analysis was performed to assess for factors impacting overall survival(OS).2.Formalin-fixed,paraffin-embedded blocks of these patients were collected.Immunohistochemical staining was performed with phosphorylated(p-)AKT,p-mTOR and p-p70S6K1.Their correlation with OS was analyzed.Results1.The study was comprised of 23 patients.At a median follow-up.of 13 months,8 patients had died,7 patients remained alive,and 8 patients were lost,6 of them was excluded from survival analysis for incomplete data.2.The average age of 23 patients was 68.3 years,and the lesions were common in the forehead,top,temporal,cheek and periorbital skin.3.The overall median survival of 17 patients was 26.0 months.One-year and 3-year OS(95%Cl)were 73.5%(51.0%-96.4%)and 21.8%(0%-57.7%),respectively.4.On univariate analysis,age younger than 70 years(vs>70 years)was associated with higher median survival(33.0 months vs 8.0 months,P=0.001).Tumors larger than 5 cm(vs<5 cm)correlates with lower median survival(13.0 months vs 33.0 months,P=0.02).5.The positive rates of p-AKT at Ser 473,p-AKT at Thr 308,p-mTOR at Ser 2448 and p-p70S6K1 at Thr 421/Ser 424 were 13.0%,78.3%,47.8%and 21.7%,respectively.And their expression was irrelevant to OS.ConclusionsCutaneous angiosarcoma of the scalp and face most commonly affects the forehead,top,temporal,cheek and periorbital skin of elderly patients.The overall prognosis remains poor,while patients who are younger and who have less extensive disease fare better.Constitutive activation of AKT/mTORC1 pathway is common in the disease,while abnormal activation of p70S6K1 is not significant.Besides,overexpression of mTORC2 is present in some cases.Our data support further study of the mTOR pathway as novel molecular targets for the treatment of cutaneous angiosarcoma of the scalp and face.