Benign Lesions in Mucosa Adjacent to Intestinal-Type Sinonasal Adenocarcinoma

Occupational exposure to wood dust is a strong risk factor for the development of intestinal-type sinonasal adenocarcinoma (ITAC); however, knowledge on possible precursor lesions or biomarkers is limited. Fifty-one samples of tumor-adjacent mucosa and 19 control samples of mucosa from the unaffected fossa of ITAC patients were evaluated for histological changes and p53 protein expression. Mild dysplasia was observed in 14%, cuboidal metaplasia in 57%, intestinal metaplasia in 8%, squamous metaplasia in 24%, and cylindrocellular hyperplasia in 53% of cases. P53 immunopositivity was generally weak occurring most frequently in squamous metaplasia. Wood dust etiology did not appear of influence on the histological changes, but p53 showed a tendency for higher positivity. Dysplasia adjacent to tumor was indicative of subsequent development of recurrence. In conclusion, precursor lesions do occur in mucosa adjacent to ITAC. This is clinically important, because it may justify the screening of high-risk individuals such as woodworkers

Assessing site quality using the National Forest Inventory

A pre-print version of the same manuscript is also available, which entitles "Assessing site quality using the National Forest Inventory"Sustainable production of wood is one of the main services provided by forest systems. Site productivity in the case of forests is often evaluated through the site quality. However, most of the works addressing the site quality have been done at local or regional scale. In this work, we aim to develop site quality models for five dominant species in Spanish forests (Fagus sylvatica, Pinus pinaster atlantica, Quercus pyrenaica, Pinus nigra, Pinus sylvestris) and create site quality maps at a national-scale from these models. First, we develop site quality models using site form (height-diameter relationship) as the reference index and the Spanish National Forest Inventory as dataset. Then, we fit spatial additive models entering physiographic and climatic variables in order to predict the site quality over the whole country. Additionally, we plot site form maps for the five species in order to describe spatial pattern in site quality at a national scale. Altitude and aspect appeared to be fundamental variables in the assessment of site quality. The accuracy of the spatial additive models ranged from 38.2% to 47.9%. The correspondence between the predicted and observed maps of site qualities is clear. Our results provide a tool which could be used by forest managers in land use planning as well as in forest policy decision-making at a national scale. We suggest that this method could be used in other countries and that the maps could be expanded to the European scale to assessing the way in which site quality varies across Europe always considering that the relationships between forest productivity and environmental variables could vary among biogeoclimatic zonesMarie Sklodowska-Curie Action, Towards a worldwide quantification of forest degradation (QUAFORD) 699884 AEI/FEDER, UE, AGL, AGL2016-76769-C2-2-R AEI/FEDER, UE, IJCI-2014-20614S

Genetic model of transformation and neoplastic progression in laryngeal epithelium

Background: To analyse genetic alterations in the transformation-progression model of larynx tumors. Methods: Copy number changes of 37 genes were analyzed by MLPA in 94 tissue samples. Results: In the smoker normal mucosa group TP53 loss was predominant, while in the precursor lesions CDKN2A loss and CDKN2D gain were most frequent. Precursor lesions with progression presented CTNNB1 loss. In the carcinoma group the most common changes were CDKN2A, MLH1, CTNNB1, CASP6 losses and RECQL4, CCND1, EMS1 gains. Positive lymph node primary tumors were related to TP53, IL1A, RB1 losses and STK11 gain. The lymph node metastases differed from their corresponding primary tumor in LMNA, RECQL4 and IGF1R losses, and N33, CDKN2D gains. Conclusions: Genetic changes and new key genes were found associated to specific steps of transformation-progression. We included new steps, not presented in the classical models: normal mucosa tobacco exposed, positive lymph node primary tumor and corresponding lymph node mestatases.projects PI02-0831 and PI07-0153 from “Fondos de Investigaciones Sanitarias” (FIS), Instituto Salud Carlos III, Spain. Project IB05-115 from Fundación de Investigación Científica y Tecnológica (FICYT), Asturias. Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD06/0020/0034) del ISCIII, Spain. IUOPA-Obra Social Caja Astur, Spain

The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma

Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials