Expression of VEGF-A/C, VEGF-R2, PDGF-α/Β, c-kit, EGFR, Her-2/Neu, Mcl-1 and Bmi-1 in Merkel cell carcinoma

Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus

“…In addition, we did not detect any mutations in 4 MCC cell lines that contain MCPyV. Consistent with previous studies, we did not find activating muta tions in PDGFRA or KIT (23,(35)(36)(37)(38). We did identify 3 tumors with p53 point substitutions, most notably in 2 specimens with absent expression of MCPyV large T antigen.…”

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

“…Evaluation of immune cell infiltrates in 21 MCC tumors, found that nearly all of the macrophages present within MCC stained positive for CD163, a marker often used to identify M2 macrophages. Immunohistochemical analysis of MCC tumor samples from 29 patients indicated that VEGF-A, VEGF-C as well as the VEGFreceptor-2 (VEGF-R2) are highly expressed (>75%) within MCC tumors (Figure 2: process 'G'), suggesting that angiogenesis via VEGF-VEGF-R ligation may be occurring in this disease [77]. Importantly, CD163 expression alone is likely insufficient to fully identify M2 macrophages [78], therefore a more detailed analysis including additional markers could more definitively characterize macrophage phenotypes in this disease.…”

Merkel Cell Carcinoma of the Gluteal Region with Ipsilateral Metastasis into the Pancreatic Graft of a Patient after Combined Kidney-Pancreas Transplantation

“…The tumour is typicallylocatedinskinregionsthatarechronicallyexposed tosun.Whenpresentonthetrunkorintheglutealregion,the tumour can appear as a deep subcutaneous skin-coloured cyst-like nodule [4], and this seemingly benign appearance candelaydiagnosisorincreasetheriskofinsufficienttumour patientswithregionallymphnodemetastases.Postoperative adjuvant chemotherapy at this stage of disease is usually indicated in high-risk patients -extensive lymph node involvement, extra-nodal expansion, and recurrence following previoustherapy [26,27].Thesecasescanalsobeextendedto includeradiotherapy [28].Mostexperiencehasbeenobtained from the use of protocols containing etoposide and carboplatinusedinthefirstlinetreatmentofsmall-celllungcarcinoma [29,27].Chemotherapyisthemainstayoftreatmentin stageIIIdiseaseandisoftencombinedwithpalliativeradiotherapy and surgical intervention when possible [22]. This treatmentisreportedtobeeffectivein60-75%ofcases,but themedianofsurvivalismeasuredinmonths [30].Therefore, therapeuticsuccessappearstodependonthedevelopmentof newtherapeuticmodalities.Inthisrespect,anumberofantibodiesagainstsurfacereceptorsoftheproteinkinasesignalling network [31,32] have been tested, as well as methods of inhibition of genes expressed in the tumour cells and responsibleforcellularproliferationandapoptosis,usingantisense oligonucleotides or microRNAs [33]. The anti-tumour effect of IFN-alpha [34] remains to be confirmed, as well as whetherAtonalhomolog1functionsasatumoursuppressor geneinMerkelcellsandthewaysinwhichitsregulationcould beutilisedforanti-cancertherapy [35].Inthefuture,prophylaxiswithvaccinationagainstMCPyVhopefullywillbepossibleinimmunosuppressedpatientswhohavenotbeenpreviouslyinfectedwithMCPyV [36].…”