Discordant results for ALK based on immunohistochemistry versus fluorescence in situ hybridization in a cohort of patients diagnosed with lung adenocarcinoma / Discordancia de los resultados para ALK basados en inmunohistoquímica e hibridación fluorescente in situ en una cohorte de pacientes diagnosticados con adenocarcinoma de pulmón

Introduction: Anaplastic lymphoma kinase (ALK) rearrangement located on the short arm of chromosome 2, region 2 and band 3 is frequent in lung cancer patients who respond to targeted therapies with ALK inhibitors Therefore, their identification has become a standard diagnostic test in patients with advanced NSCLS, as such chromosomal alterations may lead to the activation of important signalling pathways involved in cell survival and proliferation. Methods: To investigate the ALK gene status, we performed FISH and IHC assays in 18 lung adenocarcinoma patients, 12 women and 6 men, aged between 29 and 85 years. Paraffin-embedded samples were analyzed in the Pathology Department of the Hospital Universitario San Ignacio. Results: Results between the two techniques in 5 patients showed discordant patterns, being positive for FISH and negative for IHC. The borderline to define ALK positivity was set at 15%, These results present experimental evidence that the techniques differ in specific situations. Conclusions: Our findings show that it is advisable to investigate the ALK gene status in patients with suspected lung cancer using both FISH and IHC in combination.(AU)

Introducción: La reorganización de la (anaplastic lymphoma kinase) ALK ubicada en el brazo corto del cromosoma 2, región 2 y banda 3 es frecuente en los pacientes con cáncer de pulmón que responden a terapias dirigidas con inhibidores de la ALK. Por ello, su identificación se ha establecido como una prueba diagnóstica estándar en pacientes con CPCNP, ya que dichas alteraciones cromosómicas puedan determinar la activación de importantes vías de señalización implicadas en la supervivencia y proliferación celulares. Métodos: Para determinar el estatus de gen ALK se realizaron pruebas FISH e IHC en 18 pacientes con adenocarcinoma pulmonar, 12 mujeres y 6 varones, con edades comprendidas entre 29 y 85 años. Las muestras fueron analizadas en el Departamento de Anatomía Patológica del Hospital Universitario San Ignacio. Resultados: Los resultados entre ambas técnicas mostraron patrones discordantes en 5 pacientes, con positividad de FISH y negatividad con IHC. El límite para definir la positividad de ALK se estableció en el 15%. Estos resultados muestran evidencia experimental que dichas técnicas difieren en situaciones específicas. Conclusiones: Este estudio recomienda la investigación del estatus del gen ALK en los pacientes con sospecha de cáncer de pulmón, mediante la combinación de FISH e IHC.(AU)

Discordant results for ALK based on immunohistochemistry versus fluorescence in situ hybridization in a cohort of patients diagnosed with lung adenocarcinoma.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangement located on the short arm of chromosome 2, region 2 and band 3 is frequent in lung cancer patients who respond to targeted therapies with ALK inhibitors Therefore, their identification has become a standard diagnostic test in patients with advanced NSCLS, as such chromosomal alterations may lead to the activation of important signalling pathways involved in cell survival and proliferation. METHODS: To investigate the ALK gene status, we performed FISH and IHC assays in 18 lung adenocarcinoma patients, 12 women and 6 men, aged between 29 and 85 years. Paraffin-embedded samples were analyzed in the Pathology Department of the Hospital Universitario San Ignacio. RESULTS: Results between the two techniques in 5 patients showed discordant patterns, being positive for FISH and negative for IHC. The borderline to define ALK positivity was set at 15%, These results present experimental evidence that the techniques differ in specific situations. CONCLUSIONS: Our findings show that it is advisable to investigate the ALK gene status in patients with suspected lung cancer using both FISH and IHC in combination.

Phenotypic Characteristics and Copy Number Variants in a Cohort of Colombian Patients with VACTERL Association.

VACTERL association (OMIM 192350) is a heterogeneous clinical condition characterized by congenital structural defects that include at least 3 of the following features: vertebral abnormalities, anal atresia, heart defects, tracheoesophageal fistula, renal malformations, and limb defects. The nonrandom occurrence of these malformations and some familial cases suggest a possible association with genetic factors such as chromosomal alterations, gene mutations, and inherited syndromes such as Fanconi anemia (FA). In this study, the clinical phenotype and its relationship with the presence of chromosomal abnormalities and FA were evaluated in 18 patients with VACTERL association. For this, a G-banded karyotype, array-comparative genomic hybridization, and chromosomal fragility test for FA were performed. All patients (10 female and 8 male) showed a broad clinical spectrum: 13 (72.2%) had vertebral abnormalities, 8 (44.4%) had anal atresia, 14 (77.8%) had heart defects, 8 (44.4%) had esophageal atresia, 10 (55.6%) had renal abnormalities, and 10 (55.6%) had limb defects. Chromosomal abnormalities and FA were ruled out. In 2 cases, the finding of microalterations, namely del(15)(q11.2) and dup(17)(q12), explained the phenotype; in 8 cases, copy number variations were classified as variants of unknown significance and as not yet described in VACTERL. These variants comprise genes related to important cellular functions and embryonic development.