ABSTRACT
BACKGROUND: Head and neck dermatofibrosarcoma protuberans (HNDFSP) is extremely rare and not entirely understood. OBJECTIVE: To investigate the clinicopathological features of HNDFSP and identify the expression of its clinically relevant indicators, with the expectation of improving the existing treatment strategies. METHODS: A long-term follow-up of patients with HNDFSP who received treatment between 2000 and 2021 at Shanghai Ninth People's Hospital was conducted. The clinical, histological, and immunohistochemical data of the patients were retrieved and analyzed. The endpoint of the study was the incidence of significant disease-related clinical events (recurrences or metastasis). RESULTS: A total of 49 patients with HNDFSP were included in the study, with males (92.7%) predominating than females (7.3%). Eighteen patients developed recurrent disease (36.8%) after surgery, and the median time of recurrence was 48 months (interquartile, 20-74 months). Metastasis occurred in two cases (4.1%). Two patients died during follow-up, both with local recurrence, and one of them with intestinal metastasis. Post-operation radiotherapy was administered to eight patients (16.3%) and the effect in local control was remarkable. Age, tumor size, and negative margins with sufficient safety width were the main independent factors affecting the disease-free survival. Several potential targeted therapeutic indicators, including EZH2 (80.0%), EGFR (91.4%), PDGF (97.1%), PD-L1 (77.1%), and VEGF (77.1%), were positively expressed in most tumor samples. CONCLUSION: HNDFSP is rare, significantly challenging to control locally, and has a worse prognosis with current treatment strategies. Wide local excision and long-term follow-up are needed. Radiotherapy could improve the prognosis of patients with HNDFSP.
ABSTRACT
Understanding the molecular mechanisms regulating tumor dissemination and therapeutic resistance is of central importance for effective cancer therapies. Here, we report that nerve growth factor (NGF) and its receptor TrkA facilitate epithelial-mesenchymal transition (EMT) and EGFR inhibitor resistance via STAT3 activation in head and neck squamous cell carcinoma (HNSCC). Both NGF and TrkA expression were elevated in HNSCC, indicating poor clinical outcomes. NGF was highly expressed in cancer cells and nerves in perineural niche, whereas TrkA expression was higher in cancer cells with perineural invasion. The NGF/TrkA axis could promote HNSCC cell dissemination and trigger EMT via STAT3 activation. Moreover, we discovered that the NGF/TrkA axis conferred resistance to the EGFR inhibitor erlotinib via EMT processes in HNSCC cells. Blocking TrkA signaling markedly reversed EMT and sensitized HNSCC cells to erlotinib in both in vitro and in vivo models. Overall, our results demonstrate novel evidence that the paracrine NGF/TrkA axis favors EMT and confers EGFR-targeted therapeutic resistance in HNSCC.
