Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis.

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1-5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2-CD44-SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.

Reconstruction of a full-thickness upper third defect of the helix ear using a single-stage chondrocutaneous composite transposition flap.

The external ear is a crucial part of the ear's anatomy for both functional and aesthetic purposes. We present a defect after the extirpation of an invasive squamous cell carcinoma, where the final defect involved the superior third of the outer ear, missing both cartilage and skin. The regional chondrocutaneous composite transposition flap of the ipsilateral auricular concha is a one-stage technique that successfully preserves the helical rim's shape and size.

Optimizing two-stage surgery by expanding single-stage nasal reconstruction in the COVID-19 era.

The COVID-19 pandemic led to a decrease in the number of operating rooms available. Single-stage islanded forehead flaps have emerged as a good alternative to the classic frontal flap helping to diminish the surgical waiting list. We present our case series of 6 patients reconstructed with islanded forehead flaps between February and July 2020.The purpose of this report is to assess the advantages and disadvantages of this technique in order to inform which subgroup of patients may benefit from the one-stage flap, now the pandemic is better controlled.

Classic Kaposi's sarcoma treated with topical rapamycin.

Kaposi's sarcoma (KS) is an angioproliferative disorder caused by human herpesvirus 8 (HHV-8). Current research efforts have focused on the study of the relative role of KSHV-encoded genes in Kaposi's sarcomagenesis in order to identify novel mechanism-based therapies for patients suffering from this tumor. Although several viral genes have potential for KS pathogenesis, compelling data point to the KSHV-encoded G protein-coupled receptor (vGPCR) as a leading candidate viral gene for the initiation of KS. Interestingly, the oncogenic potential of vGPCR seems to correlate with its capacity to activate the mammalian target of rapamycin (mTOR) signaling pathway. Rapamycin, the prototypical inhibitor of the mTOR signaling pathway, has recently emerged as an effective treatment for KS when administered orally. In this case report, we present an immunocompetent patient with KS lesions treated with topical rapamycin achieving clinical and histologic healing after 16 weeks of treatment. The topical application of rapamycin could be a novel therapeutic option for the treatment of KS.

The effect of pulsed dye laser on high-risk basal cell carcinomas with response control by Mohs micrographic surgery.

Several reports have shown the effectiveness of pulsed dye laser (PDL) for the treatment of basal cell carcinoma (BCC). Most studies have focused on low-risk BCCs, but an important limitation has been the lack of histologic confirmation of the treatment results. The aim of this study was to assess the effectiveness of PDL in high-risk BCCs with complete histologic evaluation with Mohs micrographic surgery (MMS). Seven patients with high-risk BCCs located on the face were included. All tumors were treated with three sessions of PDL (595 nm) at 4-week intervals. The tumor and 4 mm of peripheral skin were treated with two stacked pulses with a 1-s delay, a fluence of 15 J/cm(2), a pulse duration of 2 ms, and a spot size of 7 mm. MMS was performed at least 1 month after the last PDL session including excisional tumor debulking prior to the first stage of MMS for standard histologic evaluation. Apparent complete clinical response was achieved in five of seven patients. MMS was finally performed in six patients, and clear margins were achieved after one stage of MMS. The histologic evaluation of the tumor debulking specimens showed complete clearance in four of six cases. One patient who did not undergo MMS showed a recurrence after 14 months. This is the first pilot study that demonstrates that PDL can be effective for the treatment of high-risk BCCs. Until further scientific evidence is available, treatment of high-risk BCCs should include histologic confirmation of clearance.

Melanoma: diagnosis, staging, and treatment. Consensus group recommendations.

The incidence of malignant melanoma is increasing worldwide. In Spain, its incidence is increasing faster than any other cancer type, with a 5-year survival rate of about 85%. The impact and characteristics of malignant melanoma in the Spanish population can be ascertained from the national melanoma registry of the Academia Española de Dermatología y Venereología. This review presents consensus group recommendations for the diagnosis, staging and treatment of malignant melanoma in Spain. Incidence and mortality are discussed, as well as evaluation of various prevention and treatment strategies. Prognostic factors, such as BRAF and C-KIT mutations, which are expected to become routine staging procedures over the next few years, are outlined, especially in relation to treatment options. The use of recently approved targeted agents such as ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitor, and vemurafenib, a BRAF inhibitor, in metastatic disease are also discussed.