Intravascular Large B-Cell Lymphoma and Renal Clear Cell Carcinoma as Collision Tumor: A Case Report and Review of the Literature.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of vessels. The patient usually presents with nonspecific symptoms and a remarkable deterioration in performance status. The occurrence of synchronous IVLBCL and renal cell carcinoma (RCC) is extremely rare. A right kidney tumor was found in a 72-year-old man with a history of low back pain. The kidney was enlarged, with a tumor mass measuring 4.5 × 4 × 4 cm. Sections exhibited a RCC (clear cell type, nuclear grade I). Also an extensive tumor affecting capillaries and small veins was present, positive for CD45, CD20, BCL-2, and MUM1/IRF-4, consistent with IVLBCL. The lymphoma was circumscribed to the RCC. The final diagnosis was IVLBCL with a RCC as collision tumor. After that, with neurological findings, central nervous system compromise by lymphoma was made. The patient started a first cycle of chemotherapy, progressive deterioration of the sensorium, and positive blood cultures for Klebsiella pneumoniae and Escherichia coli. The patient died 8 days later of acute respiratory failure. No autopsy was done. IVLBCL is an aggressive and systemic disease characterized by massive proliferation of tumor cells without a known primary site. Clinical identification and histopathologic diagnosis are relevant issues in the therapeutic management of these lymphomas. Until now, only one case of IVLBCL coexisting with RCC has been reported. In this article, we report a second case of IVLBCL with RCC simultaneous, as an unusual collision tumor.

Genetic diversity and phylogeographic analysis of human herpesvirus type 8 (HHV-8) in two distant regions of Argentina: Association with the genetic ancestry of the population.

BACKGROUND: The genetic diversity of persistent infectious agents, such as HHV-8, correlates closely with the migration of modern humans out of East Africa which makes them useful to trace human migrations. However, there is scarce data about the evolutionary history of HHV-8 particularly in multiethnic Latin American populations. OBJECTIVES: The aims of this study were to characterize the genetic diversity and the phylogeography of HHV-8 in two distant geographic regions of Argentina, and to establish potential associations with pathogenic conditions and the genetic ancestry of the population. STUDY DESIGN: A total of 101 HIV-1 infected subjects, 93 Kaposi's Sarcoma (KS) patients and 411 blood donors were recruited in the metropolitan (MET) and north-western regions of Argentina (NWA). HHV-8 DNA was detected by ORF-26 PCR in whole blood, saliva and FFPE tissues. Then, ORF-26 and ORF-K1 were analyzed for subtype assignment. Mitochondrial DNA and Y chromosome haplogroups, as well as autosomal ancestry markers were evaluated in samples in which subtypes could be assigned. Phylogeographic analysis was performed in the ORF-K1 sequences from this study combined with 388 GenBank sequences. RESULTS: HHV-8 was detected in 50.7%, 59.2% and 8% of samples from HIV-1 infected subjects, KS patients and blood donors, respectively. ORF-K1 phylogenetic analyses showed that subtypes A (A1-A5), B1, C (C1-C3) and F were present in 46.9%, 6.25%, 43.75% and 3.1% of cases, respectively. Analyses of ORF-26 fragment revealed that 81.95% of strains were subtypes A/C followed by J, B2, R, and K. The prevalence of subtype J was more commonly observed among KS patients when compared to the other groups. Among KS patients, subtype A/C was more commonly detected in MET whereas subtype J was the most frequent in NWA. Subtypes A/C was significantly associated with Native American maternal haplogroups (p = 0.004), whereas subtype J was related to non-Native American haplogroups (p < 0.0001). Sub-Saharan Africa, Europe and Latin America were the most probable locations from where HHV-8 was introduced to Argentina. CONCLUSIONS: These results give evidence of the geographic circulation of HHV-8 in Argentina, suggest the association of ORF-26 subtype J with KS development and provide new insights about its relationship with ancient and modern human migrations and identify the possible origins of this virus in Argentina.

[Mutational status of BRAF and histopathological characteristics in cutaneous malignant melanoma]. / Estado mutacional de BRAF y parámetros histopatológicos en melanoma maligno cutáneo.

Malignant melanoma (MM) is the more aggressive form of skin cancer with a mortality rate in Argentina 1997-2001 = 1.1/100 000 in men and 0.6 in women. BRAF proto-oncogene is focus of intense research; its mutation is one of the main tumor promoters and occurs in approximately 50% of MM. Several drugs with clinical activity on BRAF mutations have been approved. The aim of the study is to evaluate the mutational status of BRAF (exon 15) in cutaneous MM biopsies and its relationship with histopathological characteristics. We carried out an observational, retrospective study of samples fixed in formaldehyde and paraffin embedded; reviewing age, sex, diagnosis, histopathological data, tumor size and percentage, viability for molecular analysis and melanin presence. We evaluated BRAF mutations with PCR/Sanger sequencing. For statistics we used Student's t test, Chi square, Wilcoxon and Fisher's exact test. We were able to purify and sequence 76% (38/49) samples, 13/38 (34%) from women and 25/38 (66%) from men, the median age being 70 years. Most frequent location: thorax 14/35 (40%). Histological type: Superficial spreading 18/38 (47%). Clark's levels, 11/38 (29%): I-II and 27/38 (71%): III, IV and V. Breslow's median: 1.6 mm. Radial growth phase 11/38 (29%) and 27/38 (71%) vertical. Presented mutations 16/38 (42%). As reported by other authors, no association was found between the mutational state of exon 15 and clinical or histopathological parameters.

El melanoma maligno es la forma más agresiva de cáncer de piel, con una tasa de mortalidad en Argentina 1997-2001 = 1.1/100 000 en varones y 0.6 en mujeres. El proto-oncogén BRAF es foco de intensa investigación, su mutación es uno de los principales promotores tumorales y pueden presentarse en 50% de los melanomas. Se han aprobado varios fármacos con actividad clínica sobre las mutaciones BRAF. El objetivo del trabajo es evaluar el estado mutacional de BRAF (exón 15) en biopsias con melanoma maligno cutáneo y su relación con las características histopatológicas. Realizamos un estudio observacional, retrospectivo, de muestras fijadas en formol e incluidas en parafina. Revisamos edad, sexo, diagnóstico y datos histopatológicos, tamaño y porcentaje tumoral, viabilidad para análisis molecular y presencia de melanina. Evaluamos mutaciones de BRAF con PCR/secuenciación Sanger. Utilizamos test de Student, Chi cuadrado, Wilcoxon y prueba exacta de Fisher. De 49 casos se pudo purificar y secuenciar el 76% (38/49), 13/38 (34%) mujeres y 25/38 (66%) varones, edad mediana 70 años. Localización más frecuente: tórax con 14/35 (40%). Tipo histológico: extensivo superficial 18/38 (47%). Niveles de Clark, 11/38 (29%): I-II y 27/38 (71%): III, IV y V. Mediana del Breslow: 1.6 mm. Fase de crecimiento radial 11/38 (29%) y 27/38 (71%) vertical. Presentaron mutaciones 16/38 (42%). Como lo informado por otros autores, no se encontró asociación entre el estado mutacional del exón 15 y los parámetros clínicos o histopatológicos.

Estado mutacional de BRAF y parámetros histopatológicos en melanoma maligno cutáneo / Mutational status of BRAF and histopathological characteristics in cutaneous malignant melanoma

El melanoma maligno es la forma más agresiva de cáncer de piel, con una tasa de mortalidad en Argentina 1997-2001 = 1.1/100 000 en varones y 0.6 en mujeres. El proto-oncogén BRAF es foco de intensa investigación, su mutación es uno de los principales promotores tumorales y pueden presentarse en 50% de los melanomas. Se han aprobado varios fármacos con actividad clínica sobre las mutaciones BRAF. El objetivo del trabajo es evaluar el estado mutacional de BRAF (exón 15) en biopsias con melanoma maligno cutáneo y su relación con las características histopatológicas. Realizamos un estudio observacional, retrospectivo, de muestras fijadas en formol e incluidas en parafina. Revisamos edad, sexo, diagnóstico y datos histopatológicos, tamaño y porcentaje tumoral, viabilidad para análisis molecular y presencia de melanina. Evaluamos mutaciones de BRAF con PCR/secuenciación Sanger. Utilizamos test de Student, Chi cuadrado, Wilcoxon y prueba exacta de Fisher. De 49 casos se pudo purificar y secuenciar el 76% (38/49), 13/38 (34%) mujeres y 25/38 (66%) varones, edad mediana 70 años. Localización más frecuente: tórax con 14/35 (40%). Tipo histológico: extensivo superficial 18/38 (47%). Niveles de Clark, 11/38 (29%): I-II y 27/38 (71%): III, IV y V. Mediana del Breslow: 1.6 mm. Fase de crecimiento radial 11/38 (29%) y 27/38 (71%) vertical. Presentaron mutaciones 16/38 (42%). Como lo informado por otros autores, no se encontró asociación entre el estado mutacional del exón 15 y los parámetros clínicos o histopatológicos.

Malignant melanoma (MM) is the more aggressive form of skin cancer with a mortality rate in Argentina 1997-2001 = 1.1/100 000 in men and 0.6 in women. BRAF proto-oncogene is focus of intense research; its mutation is one of the main tumor promoters and occurs in approximately 50% of MM. Several drugs with clinical activity on BRAF mutations have been approved. The aim of the study is to evaluate the mutational status of BRAF (exon 15) in cutaneous MM biopsies and its relationship with histopathological characteristics. We carried out an observational, retrospective study of samples fixed in formaldehyde and paraffin embedded; reviewing age, sex, diagnosis, histopathological data, tumor size and percentage, viability for molecular analysis and melanin presence. We evaluated BRAF mutations with PCR/Sanger sequencing. For statistics we used Student's t test, Chi square, Wilcoxon and Fisher's exact test. We were able to purify and sequence 76% (38/49) samples, 13/38 (34%) from women and 25/38 (66%) from men, the median age being 70 years. Most frequent location: thorax 14/35 (40%). Histological type: Superficial spreading 18/38 (47%). Clark´s levels, 11/38 (29%): I-II and 27/38 (71%): III, IV and V. Breslow´s median: 1.6 mm. Radial growth phase 11/38 (29%) and 27/38 (71%) vertical. Presented mutations 16/38 (42%). As reported by other authors, no association was found between the mutational state of exon 15 and clinical or histopathological parameters.

Estudio patológico intraoperatorio en la cirugía tiroidea: ¿cuánto contribuye a la estrategia quirúrgica? / Intraoperative pathologic evaluation in thyroid surgery: how much does it contribute to surgical strategy?

Antecedentes: el papel del estudio patológico intraoperatorio (EPI) en cirugía tiroidea ha sido discutido largamente y es todavía motivo de controversia. Objetivo: estimar los resultados del EPI en el diagnóstico de malignidad, su relación con la biopsia por punción-aspiración preoperatoria con aguja fina (PAAF) y el estudio patológico diferido (EPD), así como su contribución al cambio en la estrategia quirúrgica en cirugía tiroidea. Material y métodos: revisión retrospectiva de las historias clínicas de 773 pacientes operados por patología tiroidea entre enero de 2014 y diciembre de 2015. En todos se efectuó EPI y EPD; a 686 (89%) pacientes también se les efectuó la biopsia por PAAF preoperatoria. Resultados: los resultados del EPI fueron benigno en 215 pacientes (27,8%), maligno en 419 (54,2%) y no definitivo en 139 (18,0%). Cuando estos resultados fueron comparados con la EPD se encontraron 19 casos (8,8%) de falsos negativos y 4 (0,95%) de falsos positivos. Considerando solo los resultados definitivos, el EPI tuvo sensibilidad 95%, especificidad 98%, valor predictivo positivo 99%, valor predictivo negativo 91% y exactitud 91%. Cuando se comparó el EPI con la PAAF preoperatoria, los valores de sensibilidad más bajos (44%) correspondieron a las categorías de Bethesda III y IV. El EPI influyó en la estrategia quirúrgica en 95 pacientes (12,28%): en 53 (6,8%), la hemitiroidectomía cambió a tiroidectomía total; en 37 (4,8%), el diagnóstico de metástasis ganglionares permitió realizar un vaciamiento modificado de cuello, y en 5 (0,6%) ocurrieron ambas situaciones. Conclusión: el EPI tuvo altos valores de utilidad diagnóstica cuando se compararon con el EPD. También se correlacionó con la PAAF preoperatoria, pero tuvo menos utilidad en las categorías Bethesda III y IV. El EPI contribuyó a cambiar la decisión de técnica quirúrgica en un grupo de pacientes y evitar una segunda operación.

Background: the role of intraoperative pathologic evaluation (IPE) in thyroid surgery has largely been discussed and it is still controversial. Objective: to estimate the results of IPE in diagnosis of malignancy, its correlation with preoperative fine needle aspiration (FNA) biopsy and permanent pathologic evaluation (PPE), and its contribution to change surgical strategy in thyroid surgery. Materials and methods: retrospective chart review of 773 patients operated on for thyroid disease between January 2014 and December 2015. All patients underwent IPE and PPE; 686 (89%) patients had also preoperative FNA biopsy. Results: IPE resulted benign in 215 patients (27.8%), malignant in 419 (54.2%) and non definitive in 139 (18.0%). When these results were compared with PPE, 19 cases were false negative (8.8%) and 4 false positive (0.95). Considering only definitive results, IPE had sensitivity 95%, specificity 98%, positive predictive value 99%, negative predictive value 91% and accuracy 91%. When IPE was compared with preoperative FNA biopsy, lowest values of sensitivity (44%) corresponded with Bethesda categories III and IV. IPE influenced surgical strategy in 95 patients (12.28%): in 53 (6.8%) hemithyroidectomy changed to total thyroidectomy, in 37 (4.8%) lymph node metastases diagnosis allowed to perform modified neck dissection, and in 5 (0.6%) both situations occurred. Conclusion: IPE had high values of diagnostic utility when compared with PPE. It also correlated with preoperative FNA biopsy, but had less utility in Bethesda categories III and IV. IPE contributed to change surgical technical decision in a subset of patients and avoid a second operation.

Performance Assessment of Epidermal Growth Factor Receptor Gene Sequencing According to Sample Size in Daily Practice Conditions.

Lung carcinoma is the main cause of cancer death worldwide. Adenocarcinoma molecular biomarkers have been discovered, and targeted therapies have been developed with encouraging results. The epidermal growth factor receptor gene is one of these biomarkers. Exons 18 to 21 should be studied in patients with advanced adenocarcinoma, who are candidates for treatment with tyrosine kinase inhibitors. The objective was to compare the performance of the determination in large and small samples in daily practice conditions, trying to adjust to published consensus guidelines. A retrospective observational study of 141 cases was carried out, with exons 19 and 21 sequencing. Sample size (small vs. large), including number of satisfactory polymerase chain reaction (PCR), sequencing, deletions, and mutations, were evaluated. In small biopsies, sample type, fragment number, and percentage of tumor per sample were analyzed. The results shown 114/141 (80.8) cases that met selection criteria; 60/114 (53%) were large (surgical) and 54/114 (47%) were small samples (19/54 endoscopic, 17/54 fine needle aspiration clots, 4/54 lymph nodes, 14/54 core and other). All large samples were satisfactory PCR, 56/60 (93%) satisfactory sequencing, and 12/56 (21%) had deletions in exon 19. Small samples were satisfactory PCRs in 50/54 (93%) cases, and satisfactory sequencing in 35/50 (65%), 8/35 (23%) showed alterations in exon 19, and 1/35 (3%) in exon 21. In conclusion, the proportion of samples unfit for the study of the epidermal growth factor receptor gene mutational status increased from 7% in large samples to 35% in small ones. Nineteen small samples were inconclusive, with cell blocks predominating, 10/19 (53%).

Lesiones por virus de papiloma humano de la vía aerodigestiva superior, incidencia de subtipos / Human papilloma virus related lesions of the upper aerodigestive tract, incidence of subtypes / Lesões por vírus do papiloma humano do trato aerodigestivo superior - Incidência de subtipos

Antecedentes: el cáncer de la vía aerodigestiva superior (CVADS), al que con frecuencia se lo engloba como “cáncer de cabeza y cuello”, tiene una incidencia aproximada de 30 nuevos casos cada 100.000 habitantes por año, habiendo presentado un aumento significativo en la última década. Los principales factores de riesgo para el CVADS siguen siendo la exposición al tabaco y el alcohol, pero el virus del papiloma humano (VPH) se ha encontrado asociado en la etiología del 20 al 25% de los CVADS, principalmente los ubicados en la región de la orofaringe. El virus tiene dos oncoproteínas, E6 y E7. E6 tiene la propiedad de unirse a la proteína celular p53, que regula la transcripción de la p21 e inhibe las quinasas ciclindependientes, las cuales son esenciales para la progresión del ciclo celular a la fase S, haciendo que la célula se replique descontroladamente...

Background: cancer of the upper aerodigestive tract (cuadt) that often encompasses it as “cancer of the head and neck, has an incidence of 30 new cases per 100,000 population per year, having presented a significant increase in the last decade. The main risk factors for CUADT remain exposure to tabaco and alcohol, but the human papillomavirus (HPV) has been found associated in the etiology of 20 to 25% of CUADT, mainly those located in the region oropharynx. The virus has two oncoproteins E6 and E7. E6 has the property of binding to cellular p53 protein that regulates transcription of p21, which inhibits cyclin dependent-kinases which are essential for cell cycle progression to S phase causing the cell to replicate uncontrollably...

Antecedentes: o câncer do trato aerodigestivo superior, que é frequentemente englobado no “câncer de cabeça e pescoço”, tem uma incidência aproximada de 30 casos novos cada 100.000 habitantes por ano, com um incremento significativo na última dé- cada. Os principais fatores de risco para o câncer de cabeça e de pescoço continuam sendo a exposição ao tabaco e ao álcool, mas o vírus do papiloma humano (VPH) é associado na etiologia de 20% até 25% dos casos de câncer do trato aerodigestivo superior, principalmente nos localizados na região da orofaringe. O vírus contém duas oncoproteínas E6 e E7. A E6 tem a propriedade de se unir à proteí- na celular p53, a qual regula a transcrição da p21, a qual inibe as quinases dependentes de ciclina que são essenciais para a progressão do ciclo celular à fase S, fazendo com que a célula se replique descontroladamente...

Enfermedad de Castleman e infección por HIV. Presentación de dos casos y revisión de la literatura / Castleman disease and HIV infection. Presentation of two cases and revision of the literature

La enfermedad de Castleman es un desorden linfoprolifera-tivo de origen aún incierto pero, en principio, relacionado con una dis-función de las células dendríticas foliculares y con una producción al-terada de distintas citoquinas, la mayor parte de ellas con actividad proinflamatoria y responsable de la sintomatología que presentan los pacientes.La relación con la presencia del HHV8, especialmente de las formas graves, ha sido ampliamente documentada en los últimos años y su desarrollo en el marco de la infección por el HIV permite una evolu-ción desafortunada de esta asociación morbosa presentando una ten-dencia importante hacia el desarrollo de patologías neoplásicas tales como la enfermedad de Kaposi y distintos tipos de linfomas.Se presentan dos casos de enfermedad de Castleman asociados a in-fección por HIV y HHV8 y se describe el contexto patogénico donde se desarrollan

Castleman ́s disease is a lymphoproliferative disorder of uncertain origin but, principally, related to dysfunction of follicular dendritic cells and impaired production of various cytokines, most of which have proinflammatory activity and are responsible for the symptoms that patients present.The relationship between Castleman ́s disease and HHV8, especially in severe forms, has been well documented in the last years. This morbid association is related to an unfortunate evolution in the context of HIV infection, presenting an increased risk of neoplastic disorders such as Kaposi ́s disease and various types of lymphomas.Two cases of Castleman ́s disease associated with HHV8 and HIV infection, and the pathogenic context in which they developed, are presented and described

Helicobacter pylori and oral pathology: relationship with the gastric infection.

Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available.

Molecular pathology of acute kidney injury in a choline-deficient model and fish oil protective effect.

PURPOSE: The aim of this work was to investigate the potential protective effects of fish oil on the basis of kidney transcriptomic data on a nutritional experimental model. METHODS: Male weanling Wistar rats were divided into four groups and fed choline-deficient (CD) and choline-supplemented (CS) diets with vegetable oil (VO) and menhaden oil (MO): CSVO, CDVO, CSMO and CDMO. Animals were killed after receiving the diets for 6 days. Total RNA was purified from the right kidney and hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array. Differentially expressed genes were analyzed. RESULTS: All CSVO, CSMO and CDMO rats showed no renal alterations, while all CDVO rats showed renal cortical necrosis. A thorough analysis of the differential expression between groups CSMO and CDMO was carried out. There were no differential genes for p < 0.01. The analysis of the differential expression between groups CSVO and CSMO revealed 32 genes, 11 were over-expressed and 21 were under-expressed in CSMO rats. CONCLUSIONS: This work was part of a large set of experiments and was used in a hypothesis-generating manner. The comprehensive analysis of genetic expression allowed confirming that menhaden oil has a protective effect on this nutritional experimental model and identifying 32 genes that could be responsible for that protection, including Gstp1. These results reveal that gene changes could play a role in renal injury.

[Clinical-pathological features and gene profile in colorectal cancer]. / Caracteres clínico-patológicos y perfil genético en el carcinoma colorrectal.

Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.

Caracteres clínico-patológicos y perfil genético en el carcinoma colorrectal / Clinical-pathological features and gene profile in colorectal cancer

El cáncer colorrectal es el tercer cáncer más frecuente en hombres y el segundo más frecuente en mujeres, con una incidencia mundial aproximada de 1.2 millones de casos nuevos por año. Nuestro objetivo primario fue estudiar la relación existente entre las características clínico-histológicas en individuos con cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS (7 mutaciones validadas), con el fin de hallar un marcador histopatológico para los tumores mutados. El objetivo secundario fue determinar cuántos pacientes tenían mutaciones adicionales en los codones 15 y 61 del gen KRAS y 600 del gen BRAF que podrían modificar el fenotipo tumoral. Fueron seleccionados 60 individuos con cáncer colorrectal (30 wild-type y 30 con mutaciones validadas en los codones 12 y 13 del gen KRAS). Se amplificaron y secuenciaron del gen KRAS los exones 2 y 3, y del gen BRAF el exón 15. La información recolectada se examinó mediante un análisis descriptivo, análisis univariado y/o análisis multivariado, según correspondiese. En conclusión, no se encontró relación entre las características clínico-histológicas de los tumores de individuos con diagnóstico de cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS. No hallamos un marcador histopatológico para los tumores mutados. En pacientes con adenocarcinomas colorrectales avanzados y KRAS wild-type resulta de interés considerar el estudio del codón 600 del gen BRAF.

Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.

Caracteres clínico-patológicos y perfil genético en el carcinoma colorrectal / Clinical-pathological features and gene profile in colorectal cancer

El cáncer colorrectal es el tercer cáncer más frecuente en hombres y el segundo más frecuente en mujeres, con una incidencia mundial aproximada de 1.2 millones de casos nuevos por año. Nuestro objetivo primario fue estudiar la relación existente entre las características clínico-histológicas en individuos con cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS (7 mutaciones validadas), con el fin de hallar un marcador histopatológico para los tumores mutados. El objetivo secundario fue determinar cuántos pacientes tenían mutaciones adicionales en los codones 15 y 61 del gen KRAS y 600 del gen BRAF que podrían modificar el fenotipo tumoral. Fueron seleccionados 60 individuos con cáncer colorrectal (30 wild-type y 30 con mutaciones validadas en los codones 12 y 13 del gen KRAS). Se amplificaron y secuenciaron del gen KRAS los exones 2 y 3, y del gen BRAF el exón 15. La información recolectada se examinó mediante un análisis descriptivo, análisis univariado y/o análisis multivariado, según correspondiese. En conclusión, no se encontró relación entre las características clínico-histológicas de los tumores de individuos con diagnóstico de cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS. No hallamos un marcador histopatológico para los tumores mutados. En pacientes con adenocarcinomas colorrectales avanzados y KRAS wild-type resulta de interés considerar el estudio del codón 600 del gen BRAF.(AU)

Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.(AU)

Caracteres clínico-patológicos y perfil genético en el carcinoma colorrectal. / [Clinical-pathological features and gene profile in colorectal cancer].

Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.

Immunohistochemical characterization of neoplastic cells of breast origin.

BACKGROUND: After skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% being breast cancer. An immunohistochemical panel with conventional and newer markers, such as mammaglobin, was selected for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with a special emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on tissue micro-array. METHODS: Twenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of diverse tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done. RESULTS: Mammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, in 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48. CONCLUSIONS: The inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin contributed to the detection of metastasis of breast cancer. The diagnostic strategy with the highest positive predictive value (88%) included hormone receptors and mammaglobin in serial manner.