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Human Papillomavirus (HPV) related Multiphenotypic Sinonasal Carcinoma (HMSC) is a rare tumor with features of both atypical squamous cell and adenoid cystic carcinoma, making diagnosis challenging. Approximately 80% of HMSC cases carries HPV type 33 followed by type 35. We present a patient with HMSC. Pathological classification was aided by immunohistochemistry (IHC). The presence of HPV-DNA was tested using PCR and HPV E6/E7 expression by RNA in situ hybridization (RNA ISH). Whole exome sequencing (WES) was used to identify somatic gene mutations and copy number alterations. A 55-year-old male presented with an HMSC in the right nostril. Histological examination showed a solid basaloid subtype with mucinous spaces and ductal structures. IHC showed positive staining for SOX-10, SMA, p40, p63, PanCK, CK8 and MYB. Diffuse positive staining for p16 was observed and PCR and RNA ISH indicated the presence of HPV type 35. The patient was treated with endoscopic surgery and radiotherapy and is currently alive and recurrence-free after 16 months of followup. WES revealed 38 somatic sequence variants and several chromosomal regions with copy number alterations, including a copy number gain at 6q23 where MYB is located. EP300, ZNF22, ZNF609 and LRIG3 are some of the genes whose mutations were indicated as probably pathogenic. We did not find mutations predictive for drug response according to the ESMO Scale for Clinical Actionability of Molecular Targets database. This is the first report of WES analysis of an HMSC, in this case associated with HPV type 35. The detected mutation in EP300 and the overexpression of MYB may serve as molecular targets for personalized therapy. [ABSTRACT FROM AUTHOR]

Objective: To determine the usefulness of specific and reliable serum biomarkers to predict cervical lymph node metastasis. Methods: A cross-sectional study of cases and controls. Thirty-nine serum samples of head and neck squamous cell carcinoma were collected from patients during neoplasm resection. Another 10 serum samples were collected from healthy individuals as a control group. Selected serum biomarkers were E-cadherin, MMP-2, MMP-9, active MMP-13, and p53 autoantibodies. Results: We found a correlation between active MMP-13 (>685 pg/mL; ROC curve analysis 95% CI for sensitivity 79.6-99.3; specificity 49.2-95.1; positive predictive value 65-100; and negative predictive value 36-100) as well as the presence of p53 autoantibodies and lymph node metastasis. Multimarker analysis using MMP-13 and p53 autoantibodies together provided better sensitivity (76%) and specificity (100%). Conclusions: The combined determination of active MMP-13 and p53 autoantibodies could improve diagnosis of lymphatic metastasis in head and neck squamous cell carcinoma and aid therapeutic decision making. [Copyright &y& Elsevier]

Monocyte-derived dendritic cells (mDC) are increasingly used as cancer vaccines. However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naïve T lymphocytes to secrete higher levels of IL-4 than DC derived from regular CD14highCD16− monocytes (16−mDC). Th1-type responses have been associated with effective antitumor responses, thus the use of mDC containing 16+mDC as cancer vaccines might be disadvantageous. Here, we evaluate the primary and memory immune response elicited in vitro by 16+mDC and 16−mDC in five patients with metastatic renal cell carcinoma vaccinated with autologous mDC pulsed with tumor lysates (TuLy) and keyhole limpet hemocyanin (KLH). After therapy, three of the five patients had stable disease. Surprisingly, patients with longer survival showed the highest amount of peripheral blood CD16+ monocytes. Analysis of KLH-specific antibodies revealed high titers of IgG2 in patients with longer survival. CD4+ T lymphocyte proliferation against KLH and TuLy increased after treatment, and some patients showed an augmented rate of CD4+ T lymphocyte proliferation against KLH (3/5) and TuLy (2/3) when 16+mDC were used as antigen presenting cells (APC). Before treatment, the IFN-γ/IL-4 ratio against TuLy and KLH was higher when using 16−mDC as APC, but after vaccination four of five patients had an increased ratio for TuLy with 16+mDC. These results suggest that the immune response elicited by 16−mDC and 16+mDC is modified when memory or naïve T cells are stimulated, and 16+mDC could favor a stronger and more beneficial antitumoral Th1 memory response in vivo. [ABSTRACT FROM AUTHOR]