High Rate of Mutations of Adhesion Molecules and Extracellular Matrix Glycoproteins in Patients with Adult-Onset Focal and Segmental Glomerulosclerosis.

(1) Background: Focal and segmental glomerulosclerosis (FSGS) is a pattern of injury that results from podocyte loss in the setting of a wide variety of injurious mechanisms. These include both acquired and genetic as well as primary and secondary causes, or a combination thereof, without optimal therapy, and a high rate of patients develop end-stage renal disease (ESRD). Genetic studies have helped improve the global understanding of FSGS syndrome; thus, we hypothesize that patients with primary FSGS may have underlying alterations in adhesion molecules or extracellular matrix glycoproteins related to previously unreported mutations that may be studied through next-generation sequencing (NGS). (2) Methods: We developed an NGS panel with 29 genes related to adhesion and extracellular matrix glycoproteins. DNA was extracted from twenty-three FSGS patients diagnosed by renal biopsy; (3) Results: The average number of accumulated variants in FSGS patients was high. We describe the missense variant ITGB3c.1199G>A, which is considered pathogenic; in addition, we discovered the nonsense variant CDH1c.499G>T, which lacks a Reference SNP (rs) Report and is considered likely pathogenic. (4) Conclusions: To the best of our knowledge, this is the first account of a high rate of change in extracellular matrix glycoproteins and adhesion molecules in individuals with adult-onset FSGS. The combined effect of all these variations may result in a genotype that is vulnerable to the pathogenesis of glomerulopathy.

Genotype Distribution Change After Human Papillomavirus Vaccination in Two Autonomous Communities in Spain.

Context: It has been more than 10 years since the human papillomavirus (HPV) vaccination program was initiated in most advanced countries. Thus, it seems necessary to change the uterine cervical cancer screening strategy. Molecular-based tests are considered essential in this scenario. Objective: We aimed to review the distribution of the HPV genotypes after the introduction of the vaccination program with Cervarix® and Gardasil 4® in two autonomous communities in Spain, looking for possible changes in distribution and the occurrence of a herd effect. Design: A cross-sectional study was performed in 45,362 samples that were processed in the Cantabria and Aragon communities during the period from 2002 to 2016. We compared the genotype distribution before and after the vaccination program was initiated. Results: Genotypes HPV6 and HPV11 have decreased significantly after the introduction of the vaccine. HPV16 has had a decrease, but not a significant one in the statistical analysis. However, HPV31, HPV52, and HPV45 have increased in percentage. A replacement phenomenon with other genotypes not included in the vaccine has been observed in our population. Conclusions: Continued surveillance is needed to provide further indication of any changes over time in the genotypes in circulation. This will be facilitated by monitoring the genotyping results from the new model of cervical screening using primary HPV DNA testing.

ETV6-NTRK3-positive parotid mammary analogue secretory carcinoma: a case report.

INTRODUCTION: Mammary analogue secretory carcinoma (MASC) is a recent discovered entity of salivary glands tumors, reported for first time in 2010. The presence of a translocation encodes the ETS variant transcription factor 6-neurotrophic tyrosine receptor kinase (ETV6-NTRK3) gene fusion differences MASC from other tumors. CASE PRESENTATION: A 68-year-old male showed a non-painful right parotid enlargement, came from dermatology service, and followed by some facial squamous cell carcinomas. A computed tomography (CT) scan showed a 1.7×1.6 cm right parotid enlargement in superficial lobe. The patient underwent a right superficial parotidectomy. The final pathology confirmed the presence of ETV6-NTRK3-positive MASC. Complete right deep parotidectomy and functional cervical emptying were performed. DISCUSSIONS AND CONCLUSIONS: It is necessary to establish an appropriated differential diagnosis between salivary gland tumors. MASC is a low-grade malignancy cancer that sometimes can evolve to a high-grade tumor that might produce local and distance dissemination. Most times, these tumors are only treated by surgical resection and evaluating by a multidisciplinary team the need of more treatments. In our case, the patient showed a primary parotid tumor, removed surgically with free edges, and being identified as MASC. We decided to underwent neck dissection and discovered a second MASC focus on cervical salivary gland; however, there was no nodal dissemination. The patient remains disease-free after 14 months from last surgery. It is important to keep studying genetic therapy targets to ETV6-NTRK3 to obtain a new therapy line to treat those cases that require.

[Peritoneal recurrence prediction for colon cancer based on immunoexpression]. / Predicción de recurrencia peritoneal mediante inmunoexpresión en cáncer de colon.

INTRODUCTION AND OBJECTIVES: Peritoneal relapse as an isolated form of recurrence in colon cancer occurs in 25% of cases during the first two years subsequent to a curative colectomy. Currently, the diagnostic limitations of imaging studies and the absence of predictive scales for peritoneal recurrence warrant "second look" surgery in high-risk patients. The aim of this study is to assess features of some epithelial-mesenchymal transition biomarkers (c-Met, IGF-1R and plexin ß1) in order to predict post-surgical peritoneal colonization and develop a mathematical model to predict carcinomatous relapse. METHODS: A retrospective study of the histopathological samples of 87 patients diagnosed with colon cancer who underwent radical resection was carried out, using immunohistochemical techniques for c-Met, IGF-1R and plexin ß1. The patients were divided into two groups; those who had presented peritoneal recurrence and those who only had risk factors for this kind of relapse. Every stained sample was assessed by the rate of stained cells and immunostaining intensity. A possible association between immunohistochemical findings and peritoneal relapse was evaluated. Statistical analysis of the biomarkers with higher prognostic value allowed a risk mathematical formula to be developed based on coefficients, providing a specific value to each biomarker and patient. RESULTS: c-Met expression in the primary tumour showed a high statistical trend (p: .074) while IGF-1 (p: .022) and plexin ß1 (p: .021) revealed a significative association with peritoneal relapse. However, the multivariate analysis selected c-Met y plexin ß1 as useful factors for a predictive mathematical model on peritoneal recurrence with a 75.8% sensitivity and 80.5% specificity in patients with a staining more than 50% for both biomarkers. CONCLUSION: c-Met and plexin B1 overexpression is related to an increased risk of peritoneal relapse in cases of colon cancer where a radical resection is feasible. The encouraging outcomes of the proposed mathematical model may prove useful clinically in the identification of candidates for carcinoprophylaxis.

Pulmonary Langerhans cell histiocytosis "de novo" after lung transplantation.

A pulmonary Langerhans cell histiocytosis is presented in a 40 year-old woman two years after bilateral lung transplantation for emphysema without any signs of Langerhans cells proliferation in the explanted lungs. A microsatellite molecular analysis showed the proliferating cells were generated in a recipient cellular clone. The patient did not quit smoking after transplantation. No signs of disease were detected in the implanted lungs before surgery. Strict control of immunosupressive drug levels stabilized the disease. A "de novo" monoclonal origin of stem cells, probably from the bone marrow is suggested. The reason she did not develop disease in the native lungs is unknown, although we suggest an interaction between tobacco or some other antigens and local cellular receptors.