Alterations in p53, Microsatellite Stability and Lack of MUC5AC Expression as Molecular Features of Colorectal Carcinoma Associated with Inflammatory Bowel Disease.

Colitis-associated colorectal carcinoma (CAC) occurs in inflammatory bowel disease (IBD) because of the "chronic inflammation-dysplasia-cancer" carcinogenesis pathway characterized by p53 alterations in the early stages. Recently, gastric metaplasia (GM) has been described as the initial event of the serrated colorectal cancer (CRC) process, resulting from chronic stress on the colon mucosa. The aim of the study is to characterize CAC analyzing p53 alterations and microsatellite instability (MSI) to explore their relationship with GM using a series of CRC and the adjacent intestinal mucosa. Immunohistochemistry was performed to assess p53 alterations, MSI and MUC5AC expression as a surrogate for GM. The p53 mut-pattern was found in more than half of the CAC, most frequently stable (MSS) and MUC5AC negative. Only six tumors were unstable (MSI-H), being with p53 wt-pattern (p = 0.010) and MUC5AC positive (p = 0.005). MUC5AC staining was more frequently observed in intestinal mucosa, inflamed or with chronic changes, than in CAC, especially in those with p53 wt-pattern and MSS. Based on our results, we conclude that, as in the serrated pathway of CRC, in IBD GM occurs in inflamed mucosa, persists in those with chronic changes and disappears with the acquisition of p53 mutations.

Gastric metaplasia as a precursor of nonconventional dysplasia in inflammatory bowel disease.

Gastric metaplasia in colonic mucosa with inflammatory bowel disease (IBD) develops as an adaptation mechanism. The association between gastric metaplasia and nonconventional and/or conventional dysplasia as precursors of colitis-associated colorectal cancer is unknown. To address this question, we retrospectively reviewed a series of 33 IBD colectomies to identify gastric metaplasia in 76 precursor lesions. We obtained 61 nonconventional and 15 conventional dysplasias. Among nonconventional dysplasia, 31 (50.8 %) were low-grade (LGD), 4 (6.5 %) were high-grade (HGD), 9 (14.8 %) had both LGD and HGD, and 17 (27.9 %) had no dysplasia (ND), while 14 (93 %) conventional dysplasias had LGD, and 1 (7 %) had LGD and HGD. Gastric metaplasia was assessed by concomitant immunoexpression of MUC5AC and loss of CDX2 staining. Expression of a p53-mut pattern was considered as a surrogate for gene mutation, and complete loss of MLH1 staining as presence of MLH1 hypermethylation. In nonconventional dysplasia, MUC5AC immunoexpression decreased as the degree of dysplasia increased, being 78 % in LGD and 39 % in HGD (p = 0.006). CDX2 was lost in epithelial glands with high expression of MUC5AC (p < 0.001). The p53-mut pattern was observed in 77 % HGD, 45 % LGD, and in 6 % with ND (p < 0.001). Neither nonconventional nor conventional dysplasia showed complete loss of MLH1 staining. Gastric metaplasia was also present in mucosa adjacent to nonconventional dysplasia with chronic changes or active inflammation. Our results show that gastric metaplasia appears in IBD-inflamed colon mucosa, it is the substrate of most nonconventional dysplasia and occurs prior to p53 alterations.

Relationship of immunohistochemistry, copy number aberrations and epigenetic disorders with BRCAness pattern in hereditary and sporadic breast cancer.

The study aims to identify the relevance of immunohistochemistry (IHC), copy number aberrations (CNA) and epigenetic disorders in BRCAness breast cancers (BCs). We studied 95 paraffin included BCs, of which 41 carried BRCA1/BRCA2 germline mutations and 54 were non hereditary (BRCAX/Sporadic). Samples were assessed for BRCA1ness and CNAs by Multiplex Ligation-dependent Probe Amplification (MLPA); promoter methylation (PM) was assessed by methylation-specific-MLPA and the expression of miR-4417, miR-423-3p, miR-590-5p and miR-187-3p by quantitative RT-PCR. IHC markers Ki67, ER, PR, HER2, CK5/6, EGFR and CK18 were detected with specific primary antibodies (DAKO, Denmark). BRCAness association with covariates was performed using multivariate binary logistic regression (stepwise backwards Wald option). BRCA1/2 mutational status (p = 0.027), large tumor size (p = 0.041) and advanced histological grade (p = 0.017) among clinic-pathological variables; ER (p < 0.001) among IHC markers; MYC (p < 0.001) among CNA; APC (p = 0.065), ATM (p = 0.014) and RASSF1 (p = 0.044) among PM; and miR-590-5p (p = 0.001), miR-4417 (p = 0.019) and miR-423 (p = 0.013) among microRNA expression, were the selected parameters significantly related with the BRCAness status. The logistic regression performed with all these parameters selected ER+ as linked with the lack of BRCAness (p = 0.001) and MYC CNA, APC PM and miR-590-5p expression with BRCAness (p = 0.014, 0.045 and 0.007, respectively). In conclusion, the parameters ER expression, APC PM, MYC CNA and miR-590-5p expression, allowed detection of most BRCAness BCs. The identification of BRCAness can help establish a personalized medicine addressed to predict the response to specific treatments.

Adenoma hipofisario: estudio de la actividad proliferativa con Ki-67 / Pituitary adenoma: study of proliferative activity with Ki-67

Antecedentes: Los adenomas hipofisarios son neoplasiasbenignas que pueden tener un comportamiento localmenteagresivo. Métodos: En el presente trabajo se analiza el significadode la actividad proliferativa mediante inmunotincióncon Ki-67 en una serie de 107 adenomas hipofisarios. Resultados:La actividad proliferativa media fue de 1,99% (rango0%-18%) y la mayoría (81%) presentaron Ki-67 <3%. Seobservó una tendencia a la asociación entre mayor nivel deKi-67 y extensión extraselar, tipo inmunohistoquímico hormonal(prolactinomas y adenomas gonadotropos), sexo masculinoy menor edad. Sin embargo, no se demostró asociaciónsignificativa con la densidad mitocondrial y la densidadmicrovascular (DMV), la actividad funcional o la apariciónde recidiva. Conclusiones: El estudio de la actividad proliferativacon Ki-67 puede definir un subgrupo de adenomashipofisarios con comportamiento localmente más agresivo

Introduction: Pituitary adenomas are benign neoplasias,but they may behave locally more aggressive.Methods: The present study analyzes the significance ofproliferative activity by Ki-67 staining in a series of 107pituitary adenomas. Results: The mean proliferative activityrate was 1.99% (range 0%-18%) and the majority(81%) showed Ki-67 <3%. We showed a trend towards ahigher Ki-67 in adenomas with extrasellar extension, hormonalsubtype (prolactinomas and gonadotroph cell adenomas),male gender and younger age. However, no significantdifferences were found between Ki-67 and mitochondrialor microvascular densities, functional activity orrecurrence. Conclusions:We conclude that the proliferativeactivity evaluated by Ki-67 can define a subset of pituitaryadenomas with a more aggressive behavior

Lesiones de células columnares y atipia epitelial plana de la mama / Columnar cell lesions and flat epithelial atypia of the breast

La frecuente identificación de lesiones de célulascolumnares en biopsias mamarias realizadas por microcalcificacionesmamográficas ha determinado un renovadointerés en su adecuada clasificación y significado biológicoy clínico. En la presente revisión se describen los criteriosde clasificación, así como los principales problemas dediagnóstico diferencial, significado biológico y actitud clínicaante su diagnóstico

The frequent identification of columnar cell lesions inbreast biopsies performed due to microcalcifications mammograficalydetected, has determined an increasing interestfor the adequate classification, as well as their biologicaland clinical significance. In the present review, we describethe classification criteria and the main difficulties for thedifferential diagnosis, biological significance and clinicalmanagement of these lesions

Carcinoma colorrectal con alteración de la vía reparadora. Claves para su identificación y relevancia clínica / Mismatch-repair deficiency colorrectal carcinoma. Identification keys and clinical relevance

Un 7,5% de los carcinomas colorrectales (CCR) en España presenta alteraciones del sistema de reparación de errores de replicación del ADN (mismatch repair, MMR). De ellos, un 20% se desarrolla en pacientes que presentan el síndrome de Lynch. Para identificar a estos pacientes se utilizan criterios clínicos, moleculares, histopatológicos e inmunohistoquímicos. El análisis inmunohistoquímico de las proteínas reparadoras (MLH1, MSH2, MSH6 y PMS2) ha demostrado ser una técnica válida para la detección de tumores con alteración del MMR. La generalización del uso de la inmunohistoquímica hace que actualmente el patólogo desempeñe un papel fundamental en la identificación de pacientes con síndrome de Lynch

Colorectal carcinoma (CRC) in Spain shows mismatchrepair deficiency (MMR+) reaching a 7.5%. Twenty percent of them presents in Lynch syndrome. Identification of these patients is based on clinical, molecular, histopathologic and immunohistochemical criteria. Immunohistochemical analysis of mismatch-repair proteins (MLH1, MSH2, MSH6, and PMS2) is a valid technique to detect MMR+ tumors. The generalized use of immunohistochemistry confers to pathologists a fundamental role in the identification of patients with Lynch syndrome

Fiebre en paciente con trasplante renal / Fever in a patient with a renal transplant

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Aracnoiditis osificante: una causa infrecuente de compresión medular / Arachnoiditis ossificans: an uncommon cause of medular compression

Aportamos un nuevo caso de aracnoiditis osificante, sugerido a partir de los hallazgos en resonancia magnética y confirmado histopatológicamente después de la cirugía descompresiva. Revisamos la bibliografía sobre esta patología, haciendo hincapié en su diagnóstico radiológico por resonancia magnética, así como en los aspectos clínicos y en la actitud terapéutica.