Significado y dimensiones actuales de los tumores estromales gastro-intestinales (GIST)

Desde que en 1983 se utilizara por primera vez el término GISTs hasta hoy, se ha profundizado mucho en su conocimiento, comentándose aquí tres aspectos de actualidad: -Heterogenidad molecular: hasta hace poco se consideraba que los GISTs podían presentar dos tipos de mutaciones excluyentes, en KIT (75%) y PDGFR (10%). Hoy sabemos que existen también mutaciones en SDH, en KRAS/BRAF y en NF1, además de casos con fusiones génicas (s.t. de FGFR-1) y mutaciones puntuales en MAX, BCOR y APe. -Origen de los GISTs y progresión tumoral: Hirota et al (1998) señaló su origen en las células intersticiales de Cajal, aunque las que tienen potencial oncogénico son las sensibles a la transformación por CKIT y expresan el factor de transformación ETV1, cuya trasncripción se regula por KIT activado. Además, en la promoción tumoral es necesario la colaboración de otros factores. El acontecimiento inicial es la activación del oncogen KIT en el subtipo de CIC-ETV1 que conduce solo a una hiperplasia; para que progrese el crecimiento son necesarios cambios adicionales como deleciones del 14q, o del 22q. En la evolución se presentan otras deleciones adicionales en los genes lp,9p 15q Y Xplp 9p y 15q. Entre los genes implicados están MAX que interactúa con el gen MYC y causa desregulación de la expresión de p16 asociándose a progresión a tumor de riesgo intermedio y alto. Otro gen es lNll que regula negativamente el celular. En el segmento del XP está la distrofina que se asocia en el 90% con el desarrollo de metástasis. -GISTs de tipo pediátrico: se caracterizan por malfuncionamiento del complejo SDH y tienen características bioevolutivas diferentes. Afectan a jóvenes, sobre todo mujeres, en estómago, multifocales, con frecuentes metástasis linfáticas, exhiben mutaciones en SDH, expresan CD117 y DOGl, tienen un curso clínico indolente y no responden al imatinib. La mayoría de los casos se asociación a dos síndromes definidos: triada de Carney y síndrome de Carney-Stratakis.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A study of the suitability of autoencoders for preprocessing data in breast cancer experimentation

Breast cancer is the most common cause of cancer death in women. Today, post-transcriptional protein products of the genes involved in breast cancer can be identified by immunohistochemistry. However, this method has problems arising from the intra-observer and inter-observer variability in the assess ment of pathologic variables, which may result in misleading conclusions. Using an optimal selection of preprocessing techniques may help to reduce observer variability. Deep learning has emerged as a powerful technique for any tasks related to machine learning such as classification and regression. The aim of this work is to use autoencoders (neural networks commonly used to feed deep learning architec tures) to improve the quality of the data for developing immunohistochemistry signatures with prognos tic value in breast cancer. Our testing on data from 222 patients with invasive non-special type breast carcinoma shows that an automatic binarization of experimental data after autoencoding could outper form other classical preprocessing techniques (such as human-dependent or automatic binarization only) when applied to the prognosis of breast cancer by immunohistochemical signaturesMinisterio de Economía y Competitividad TIN2014-55894-C2-1-

Expression of P-glycoprotein and metallothionein in gastrointestinal stromal tumor and leiomyosarcomas. Clinical implications

We investigated the expression of P-glycoprotein (P-GP) and metallothionein (MT) in a series of 92 GIST and 14 gastrointestinal leiomyosarcomas (GILMS) with the purpose to expand our knowledge on the biological bases of GIST chemo-resistance and to ascertain their significance in patients’ prognosis. P-GP expression was more frequent in GIST than in GI-LMS (83.7% vs. 21.4%, p<0.001), with no difference between low- and high-risk GIST (p=1.000) or low- and high-grade GI-LMS (p=0.538). P-GP expression was unrelated to anatomic location (gastric vs. intestinal) in GIST (39/45 vs. 35/43, p=0.770) and in GI-LMS (0/2 vs. 2/6, p=1.000). MT expression was non-significantly higher in GI-LMS than in GIST (35.7% vs. 14.1%, p=0.060), with no difference between low- and high-risk GIST (p=1.000) or low- and high-grade GI-LMS (p=1.000). MT expression was unrelated to the anatomic location (gastric vs. intestinal) in GIST (7/45 vs. 6/43) and GI-LMS (0/2 vs. 1/6) (p=1.000 and p=0.1000, respectively). Overall tumor-specific survival (p< 0.001) and disease-free survival (p<0.001) were different in GIST as compared with GI-LMS, and the number of events was higher in GI-LMS. When the survival analysis took into consideration P-GP or MT expression, the overall survival in GIST was influenced by the expression of MT (p=0.021) but not by that of P-GP (p=0.638). However, in GI-LMS, P-GP expression influenced disease-free survival (p=0.050); in addition, it is important to recognize the limited value of these results because of the low number of cases involved in the study. Differential expression of P-GP and MT might explain the known variability in response to systemic chemotherapy in these tumors. Detection of P-GP and MT seems to add certain prognostic value in GIST (MT) or GI-LMS (P-GP)

Epidemiology of Barrett's esophagus and esophageal adenocarcinoma in Spain. A unicentric study.

Barrett's esophagus (BE) is an acquired disease defined by the presence of intestinal metaplasia with goblet cells in the distal esophagus. The prevalence of BE has increased dramatically over the last years. The primary aims of the study were to analyze the characteristics of BE and esophageal adenocarcinoma (EAC) in a Spanish health district during a follow-up period. Sociodemographic factors, alcohol consumption and cigarette smoking were analyzed. We also studied the histological behavior and cause of death in each group. In the present study 430 patients were included, 338 with BE and 92 with EAC. Incidence rates have risen from 2.25 and 1.25 per 100,000 inhabitants in 1996 to 6.5 and 4.75 per 100,000 in 2011, respectively. In the EAC group, male gender, age and alcohol consumption were higher in comparison to the BE group, and the overall survival was 23 months. In the BE group, the main causes of death were non-esophageal cancer and cardiovascular disease. The incidence and prevalence rates of AEC and BE have risen over the past years. Risk factors for these conditions were male gender, age and alcohol consumption. Long BE (> 3 cm) is involved in dysplasia progression. AEC diagnosis mainly occurs after neoplasia is detected and, in a few cases, due to a previous BE. Cardiovascular diseases and non-esophageal cancers have been found to be the main cause of death in BE patients

MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression

Emerging evidence suggests that BRCA1 pathway contributes to the behavior of sporadic triple negative breast cancer (TNBC), but little is known about the mechanisms underlying this association. Considering the central role that microRNAs (miRNAs) play in gene expression regulation, the aim of this study was to identify miRNAs specifically deregulated in TNBC and investigate their involvement in BRCA1 regulation. Using locked nucleic acid (LNA)-based microarrays, expression levels of 1919 miRNAs were measured in paraffin-embedded tissues from 122 breast tumors and 11 healthy breast tissue samples. Differential miRNA expression was explored among the main subtypes of breast cancer, and 105 miRNAs were identified as specific for triple negative tumors. In silico prediction revealed that miR-498 and miR-187-5p target BRCA1, and these results were confirmed by luciferase reporter assay. While miR-187-5p was found overexpressed in a luminal B cell line, miR-498 was highly expressed in a triple negative cell line, Hs578T, and its expression was negatively correlated with the levels of BRCA1. We functionally demonstrated that miR-498 inhibits BRCA1 in breast cancer cell lines, and showed that inhibition of miR-498 led to reduced proliferation in the triple negative cell line Hs578T. Our results indicate that miR-498 regulates BRCA1 expression in breast cancer and its overexpression could contribute to the pathogenesis of sporadic TNBC via BRCA1 downregulation.We thank all members of the Human Cancer Genetics Programme of the Spanish National Cancer Research Centre for all their support. We want to particularly acknowledge the patients, the INCLIVA BioBank (PT13/0010/0004) integrated in the Spanish National Biobanks Network, and Pablo Isidro Marrón, coordinator of Biobanco del Principado de Asturias, for their collaboration. This work has been funded by grants from the Spanish Ministry of Economy and Competitiveness (INNPRONTA LIFE project) and FIS PI11/01059 (BM-D).S

Epidemiology of Barrett's esophagus and esophageal adenocarcinoma in Spain: a unicentric study

Background: Barrett's esophagus (BE) is an acquired disease defined by the presence of intestinal metaplasia with goblet cells in the distal esophagus. The prevalence of BE has increased dramatically over the last years. Aims: The primary aims of the study were to analyze the characteristics of BE and esophageal adenocarcinoma (EAC) in a Spanish health district during a follow-up period. Methodology: Sociodemographic factors, alcohol consumption and cigarette smoking were analyzed. We also studied the histological behavior and cause of death in each group. Results: In the present study 430 patients were included, 338 with BE and 92 with EAC. Incidence rates have risen from 2.25 and 1.25 per 100,000 inhabitants in 1996 to 6.5 and 4.75 per 100,000 in 2011, respectively. In the EAC group, male gender, age and alcohol consumption were higher in comparison to the BE group, and the overall survival was 23 months. In the BE group, the main causes of death were non-esophageal cancer and cardiovascular disease. Conclusions: The incidence and prevalence rates of AEC and BE have risen over the past years. Risk factors for these conditions were male gender, age and alcohol consumption. Long BE (> 3 cm) is involved in dysplasia progression. AEC diagnosis mainly occurs after neoplasia is detected and, in a few cases, due to a previous BE. Cardiovascular diseases and non-esophageal cancers have been found to be the main cause of death in BE patients