RESUMO
The WHO Classification of Lung Tumors (2015) established the use of immunohistochemical stainings for resection specimens, however, detailed recommendations had been missing. Now, an international expert panel has summarized key questions for daily routine practice and provided recommendations to assist the community in the appropriate use of immunohistochemistry in this context. This article provides an overview of the most important aspects.
Assuntos
Imunofenotipagem/métodos , Neoplasias Pulmonares , Humanos , Imuno-HistoquímicaRESUMO
Background: Reported prevalence of driver gene mutations in non-small-cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the European Thoracic Oncology Platform Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathologic features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods: Clinically annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform. Mutant-allele detection sensitivity is >1% for most of the â¼150 (13 genes) mutations covered in the multiplex test. Results: Multiplex testing has been carried out in 2063 (76.2%) of the 2709 Lungscape cases (median follow-up 4.8 years). FFPE samples mostly date from 2005 to 2008, yet recently extracted DNA quality and quantity was generally good. Average DNA yield/case was 2.63 µg; 38 cases (1.4%) failed QC and were excluded from study; 95.1% of included cases allowed the complete panel of mutations to be tested. Most common were KRAS, MET, EGFR and PIK3CA mutations with overall prevalence of 23.0%, 6.8%, 5.4% and 4.9%, respectively. KRAS and EGFR mutations were significantly more frequent in adenocarcinomas: PIK3CA in squamous cell carcinomas. MET mutation prevalence did not differ between histology groups. EGFR mutations were found predominantly in never smokers; KRAS in current/former smokers. For all the above mutations, there was no difference in outcome between mutated and non-mutated cases. Conclusion: Archival FFPE NSCLC material is adequate for multiplex mutation analysis. In this large, predominantly European, clinically annotated stage I-III NSCLC cohort, none of the mutations characterized showed prognostic significance.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/biossíntese , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Análise Mutacional de DNA/métodos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex/métodos , Estadiamento de Neoplasias , Prevalência , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-met/biossíntese , Proteínas Proto-Oncogênicas c-met/genética , Fumar/genética , Adulto JovemRESUMO
The new concept of spread through air spaces (STAS) was introduced for pulmonary adenocarcinomas in the 2015 WHO classification for lung cancer. Yet, available data demonstrate that STAS is of high prognostic impact and associated with specific clinic-pathological characteristics. This article provides a comprehensive overview of recent developments in this field.
Assuntos
Neoplasias Pulmonares , Inoculação de Neoplasia , Humanos , Invasividade Neoplásica , PrognósticoRESUMO
Recently a new TNM classification for tumors of the lung was published, encompassing some relevant changes, for example how to deal with multiple lung tumors. This article comprehensively describes respective changes. Furthermore, background information on how the new TNM classification was built and what should be done in the future to further improve prognosis and outcome prediction is reviewed.
Assuntos
Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias/métodos , Humanos , Pulmão/patologia , Linfonodos/patologia , Gradação de Tumores , Neoplasias Primárias Múltiplas/patologia , PrognósticoRESUMO
The residual (R) tumor classification is an essential, even if facultative component of the TNM classification; however, it should alway be included in the pathology results of certified lung cancer centers. In discussions it becomes clear again and again that different hospitals and departments have different approaches and interpretations with respect to the R status after lung resection. We carried out a questionnaire-based survey of pathologists (with specialization in pulmonary pathology) and thoracic surgeons on the application of the R classification for lung tumors. The results of the survey revealed the different perceptions of the participating centers with respect to application and interpretation, which results in divergent decisions for adjuvant therapy and complicates the comparability of national and international studies. The results of the survey are especially valuable because all participants have a high level of expertise in the field of thoracic pathology and the data reflect the current practice in certified lung cancer centers. It appears to be necessary to examine the application and interpretation of the R classification for lung cancer more closely in an interdisciplinary exchange and to produce a catalogue of criteria to guarantee at least a better national standardization.
Assuntos
Institutos de Câncer , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Neoplasia Residual/classificação , Neoplasia Residual/patologia , Inquéritos e Questionários , Certificação , Terapia Combinada , Técnicas de Apoio para a Decisão , Humanos , Comunicação Interdisciplinar , Colaboração Intersetorial , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Neoplasia Residual/terapiaRESUMO
BACKGROUND: Antibodies against PD-1 and PD-L1 can cause strong and durable anti-tumor immune responses in non-small cell lung cancer (NSCLC). Immunohistochemistry for PD-L1 (PD-L1 IHC) was tested as a predictive biomarker. Several IHC assays and interpretation criteria were developed in parallel. AIM: The clinical significance of PD-L1 IHC in NSCLC and the optimum method for staining and interpretation of the results are the subject of ongoing studies. The diagnostic application of immunotherapy in NSCLC necessitates harmonization of PD-L1 IHC to obtain evidence for guidelines; therefore, a consensus opinion on a well-founded diagnostic mode of testing should be defined based on published studies and the results of the first German PD-L1 IHC harmonization study. METHODS: 1. Summary of the current data situation. 2. Evaluation of the first German PD-L1 IHC harmonization study (centralized, staining with PD-L1 IHC analogous to studies, 15 cases of NSCLC, 4 IHC study assays [288, 22C3, SP142 and SP263] and scoring by 9 pathologists). RESULTS: The use of PD-L1 IHC in NSCLC is suitable for identification of patients with an increased probability of a clinical benefit from immunotherapy. The various proportional cut-offs used to interpret the staining results can be summarized in a total score, which can be reproducibly assessed. The staining patterns of the four assays investigated were, however, not congruent in all situations. DISCUSSION: In principle, the use of PD-L1 IHC for assessment of the expression in tumor cells is a reliably determinable biomarker. Evaluation algorithms should be based on published clinical trials. For NSCLC approvals with obligatory PD-L1 IHC are to be expected but it remains to be seen to what extent PD-L1 IHC will be implemented in the clinical routine.
Assuntos
Antígeno B7-H1/análise , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Algoritmos , Anticorpos Monoclonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imuno-Histoquímica , Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Valor Preditivo dos Testes , PrognósticoRESUMO
The EML4-ALK pathway plays an important role in a significant subset of non-small cell lung cancer patients. Treatment options such as tyrosine kinase inhibitors directed against the EML4-ALK signalling pathway lead to improved progression free and overall survival. These therapeutic options are chosen on the basis of the identification of the underlying genetic signature of the EML-ALK translocation. Efficient and easily accessible testing tools are required to identify the patients in time. While FISH techniques have been implemented to characterize this translocation for some time, the implementation of this testing is hampered by its broad use of resources. Immunohistochemical techniques to identify and screen for EML4-ALK translocations may play an important role in the near future. This consensus paper offers recommendations of the sequence and quality of the respective test approaches which are validated on the basis of the current literature.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Hibridização in Situ Fluorescente/normas , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico , Biópsia/métodos , Biópsia/normas , Carcinoma Pulmonar de Células não Pequenas/patologia , Diagnóstico Diferencial , Medicina Baseada em Evidências , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Testes Genéticos/normas , Alemanha , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/normas , Hibridização in Situ Fluorescente/métodos , Neoplasias Pulmonares/patologia , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Guias de Prática Clínica como Assunto , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) currently is one oft the most common reasons for chronic liver injury in the western world. In the European and American population the prevalence is up to 30â%. The medical supply of German patients with NAFLD is variable and has not been analyzed to date. METHODS: We sent questionnaires to all university liver centers in Germany (11 questions) concerning the medical supply of patients with NAFLD. Questions included the rate of patients with fatty liver disease in the outpatient clinics, metabolic comorbidities and the kind of assignment. Besides that, individual clinical standards were documented. We compared longitudinal changes between 2008 and 2013. RESULTS: The return rate of questionnaires was 65â% (nâ=â20). Analysis showed that the portion of NAFLD patients in the university outpatient clinics had increased between 2008 and 2013 with the predominant part of patients being assigned from external practitioners and not from internal departments of the hospital. Only few patients were assigned by diabetologists or endocrinologists, but on the other hand most liver outpatient clinics investigated their NAFLD patients for metabolic disorders. Cooperation between liver outpatient clinics and other medical services was moderate and was rated average, joint conferences were held rarely. Follow-up visits of patients with NAFLD take place regularly in all centers, however based on different criterions. A consistent algorithm concerning risk assessment and invasive workup does not exist. CONCLUSION: The awareness concerning patients with NAFLD seems to have grown in recent years. Nevertheless, the medical supply of these patients is quite heterogenous and consistent standards do not exist. Therefore, a common guidline is urgently required.
Assuntos
Gastroenterologia/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Pacientes/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Carga de Trabalho/estatística & dados numéricos , Alemanha/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Prevalência , Revisão da Utilização de Recursos de SaúdeRESUMO
Tumor diagnostics are based on histomorphology, immunohistochemistry and molecular pathological analysis of mutations, translocations and amplifications which are of diagnostic, prognostic and/or predictive value. In recent decades only histomorphology was used to classify lung cancer as either small (SCLC) or non-small cell lung cancer (NSCLC), although NSCLC was further subdivided in different entities; however, as no specific therapy options were available classification of specific subtypes was not clinically meaningful. This fundamentally changed with the discovery of specific molecular alterations in adenocarcinoma (ADC), e.g. mutations in KRAS, EGFR and BRAF or translocations of the ALK and ROS1 gene loci, which now form the basis of targeted therapies and have led to a significantly improved patient outcome. The diagnostic, prognostic and predictive value of imaging, morphological, immunohistochemical and molecular characteristics as well as their interaction were systematically assessed in a large cohort with available clinical data including patient survival. Specific and sensitive diagnostic markers and marker panels were defined and diagnostic test algorithms for predictive biomarker assessment were optimized. It was demonstrated that the semi-quantitative assessment of ADC growth patterns is a stage-independent predictor of survival and is reproducibly applicable in the routine setting. Specific histomorphological characteristics correlated with computed tomography (CT) imaging features and thus allowed an improved interdisciplinary classification, especially in the preoperative or palliative setting. Moreover, specific molecular characteristics, for example BRAF mutations and the proliferation index (Ki-67) were identified as clinically relevant prognosticators. Comprehensive clinical, morphological, immunohistochemical and molecular assessment of NSCLCs allow an optimized patient stratification. Respective algorithms now form the backbone of the 2015 lung cancer World Health Organization (WHO) classification.
Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Adenocarcinoma/genética , Adenocarcinoma/terapia , Algoritmos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Análise Mutacional de DNA , Progressão da Doença , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular , Prognóstico , Translocação GenéticaRESUMO
Lung cancer is the prototypical tumor entity for the development of new diagnostic and individualized therapeutic strategies based on molecular patient stratification. Developments in this field specifically concentrate on predictive biomarkers for the response to conventional therapeutic agents, novel drugs targeting specific mutations and also new immunomodulatory drugs. The multitude of upcoming new predictive biomarkers requires the development and implementation of efficient test strategies and comprehensive technical methods, specifically when tissue restrictions inherent to lung cancer diagnostics are also taken into account. Novel procedures and technical aspects of these issues are discussed in this review.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Marcadores Genéticos/genética , Técnicas de Diagnóstico Molecular , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia , Pulmão/patologia , Medicina de Precisão , PrognósticoRESUMO
AIM: Summary of prevalence, testing and treatment approaches in patients with non-small cell lung cancer (NSCLC) and ROS1 activation. METHODS: Internet-based search for clinical and preclinical studies as well as search for ongoing studies in web-based databases. RESULTS: ROS1 translocations lead to tyrosine kinase activation and can be detected in 1â-â2% of all NSCLC and in 3â-â6% of pulmonary adenocarcinoma patients, respectively, using in situ hybridization techniques. RESULTS from phase I clinical studies using the ROS1 inhibitor crizotinib indicate response rates of 70â-â80% and a median progression-free survival of about 19 months. The therapy was generally well tolerated. CONCLUSIONS: NSCLC harbouring ROS1-translocations can be treated with targeted therapy leading to promising response and survival in patients. Hence, these alterations should be included into current molecular testing panels in stage IV pulmonary adenocarcinomas.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Translocação Genética/genética , Medicina Baseada em Evidências , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Prevalência , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Fatores de RiscoRESUMO
BACKGROUND: Uncontrolled proliferation is a hallmark of malignant tumour growth. Its prognostic role in non-small cell lung cancer (NSCLC) has been investigated in numerous studies with controversial results. We aimed to resolve these controversies by assessing the Ki-67 proliferation index (PI) in three large, independent NSCLC cohorts. METHODS: Proliferation index was retrospectively analysed by immunohistochemistry in a cohort of 1065 NSCLC and correlated with clinicopathological data including outcome and therapy. RESULTS were validated in two independent cohorts of 233 squamous cell carcinomas (SQCC) and 184 adenocarcinomas (ADC). RESULTS: Proliferation index (overall mean: 40.7%) differed significantly according to histologic subtypes with SQCC showing a mean PI (52.8%) twice as high as ADC (25.8%). In ADC PI was tightly linked to growth patterns. In SQCC and ADC opposing effects of PI on overall (OS), disease-specific and disease-free survival were evident, in ADC high PI (optimised validated cut-off: 25%) was a stage-independent negative prognosticator (hazard ratio, HR OS: 1.56, P=0.004). This prognostic effect was largely attenuated by adjuvant radio-/chemotherapy. In SQCC high PI (optimised validated cut-off: 50%) was associated with better survival (HR OS: 0.65, P=0.007). CONCLUSIONS: Our data demonstrate that PI is a clinically meaningful biomarker in NSCLC with entity-dependent cut-off values that allow reliable estimation of prognosis and may potentially stratify ADC patients for the need of adjuvant therapy.
Assuntos
Adenocarcinoma/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Escamosas/secundário , Proliferação de Células , Antígeno Ki-67/análise , Neoplasias Pulmonares/patologia , Adenocarcinoma/química , Adenocarcinoma/terapia , Carcinoma Pulmonar de Células não Pequenas/química , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/química , Neoplasias Pulmonares/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The diagnostics of pulmonary neoplasms has considerably changed in recent years. Based on large-scale molecular characterization studies and the development of targeted therapies, precise morphological, immunohistochemical and molecular pathological tumor subtyping is now of utmost importance for evidence-based treatment decisions. This review highlights recent developments in morphological and immunohistochemical subtyping of pulmonary neoplasms, concepts of tumor progression and provides a preview of relevant changes of the forthcoming new WHO classification, which is expected to be published in 2015. It becomes apparent that a 3-step diagnostic procedure based on morphology, immunohistochemistry and molecular pathology is important to meet the requirements of an increasingly more complex, interdisciplinary care of lung cancer patients and to allow reliable, clinically meaningful tumor diagnosis.
Assuntos
Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Pulmão/patologia , Organização Mundial da Saúde , HumanosRESUMO
Lung cancer is the most frequent cause of cancer-related death in Germany in men and women alike. While in the last decades a classification of epithelial lung tumors into non-small cell and small cell lung cancer was clearly sufficient from the therapeutic viewpoint, the dawn of the era of personalized medicine together with tremendous developments in the field of high throughput technologies have led to a molecular individualization of these tumors and, even more important, to a molecularly defined individualization of tumor therapy. This development resulted in the definition of a wide array of molecularly divergent tumor families. In this article we will give an overview on relevant molecular alterations in non-small cell lung cancers, comprising adenocarcinomas, squamous cell carcinomas and large cell carcinomas and also small cell carcinomas and carcinoids. Besides some similarities data gathered in the last few years specifically highlighted the immense diversity of molecular alterations that might underlie tumorigenesis of lung neoplasms. The knowledge on how to detect these alterations is of utmost importance in pathology, as treatment decisions are increasingly based on their presence or absence, putting molecular pathology in the central focus of the novel era of personalized medicine in oncology.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Pequenas/classificação , Carcinoma de Células Pequenas/terapia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Progressão da Doença , Humanos , Imuno-Histoquímica , Pulmão/patologia , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/terapia , Patologia Molecular , Medicina de Precisão , Organização Mundial da SaúdeRESUMO
BACKGROUND: Biliary tract cancers (BTC) are relatively rare malignant tumours with poor prognosis. It is known from other solid neoplasms that antitumour inflammatory response has an impact on tumour behaviour and patient outcome. The aim of this study was to provide a comprehensive characterisation of antitumour inflammatory response in human BTC. METHODS: Tumour-infiltrating T lymphocytes (CD4+, CD8+, and Foxp3+), natural killer cells (perforin+), B lymphocytes (CD20+), macrophages (CD68+) as well as mast cells (CD117+) were assessed by immunohistochemistry in 375 BTC including extrahepatic (ECC; n=157), intrahepatic (ICC; n=149), and gallbladder (GBAC; n=69) adenocarcinomas. Overall and intraepithelial quantity of tumour-infiltrating immune cells was analysed. Data were correlated with clinicopathological variables and patient survival. RESULTS: The most prevalent inflammatory cell type in BTC was the T lymphocyte. Components of the adaptive immune response decreased, whereas innate immune response components increased significantly in the biliary intraepithelial neoplasia - primary carcinoma - metastasis sequence. BTC patients with intraepithelial tumour-infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes showed a significantly longer overall survival. Number of total intraepithelial tumour-infiltrating Foxp3+ regulatory T lymphocytes (HR: 0.492, P=0.002) and CD4+ T lymphocytes (HR: 0.595, P=0.008) were tumour grade- and UICC-stage-independent prognosticators. The subtype-specific evaluation revealed that the tumour-infiltrating lymphocytic infiltrate is a positive outcome predictor in ECC and GBAC but not in ICC. CONCLUSION: Our findings characterise the immune response in cholangiocarcinogenesis and identify inflammatory cell types that influence the outcome of BTC patients. Further, we show that BTC subtypes show relevant differences with respect to density, quality of inflammation, and impact on patient survival.
Assuntos
Adenocarcinoma/diagnóstico , Neoplasias do Sistema Biliar/diagnóstico , Linfócitos do Interstício Tumoral/fisiologia , Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/imunologia , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/cirurgia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Análise Serial de TecidosRESUMO
In recent years the classification of pulmonary cancer has seen a paradigm shift with respect to both morphological as well as molecular aspects. On the morphological side this includes novel criteria for tumor classification from biopsy material based on morphological and immunohistochemical aspects as well as a novel classification based on morphological patterns for pulmonary adenocarcinomas. In addition, this new classification now includes adenocarcinoma in situ as well as minimally invasive adenocarcinoma as novel entities and a variety of novel adenocarcinoma subtypes. This reclassification was accompanied and complemented by tremendous developments in the field of lung cancer genomics which paved the way for now widely established predictive molecular markers, e.g. epidermal growth factor receptor (EGFR) mutations and EML4-ALK translocations and will certainly lead to a variety of novel predictive markers not only for pulmonary adenocarcinoma but also for other pulmonary neoplasms.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/patologia , Marcadores Genéticos/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Biópsia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Receptores ErbB/genética , Humanos , Queratina-5/genética , Queratina-6/genética , Queratina-7/genética , Pulmão/patologia , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Valor Preditivo dos Testes , Serina Endopeptidases/genética , Fatores de TranscriçãoRESUMO
BACKGROUND: Personalized medicine is becoming standard for the treatment of non-small-cell lung cancer. For example, patients with activating EGFR mutations or EML4-ALK translocations largely benefit from targeted therapies with tyrosine kinase inhibitors with better response rates and progression-free survival compared to standard chemotherapy regimens. However, the application of the respective molecular biomarker analyses requires great expertise in the handling of different cell and tissue specimens. A major challenge for reliable analyses is the usually low amount of tumor material. There are currently relatively few standardized and evidence-based guidelines for the processing and analysis of respective specimens as well as for interpretation of the test results. MATERIALS AND METHODS: To establish a basis for standardized predictive cytopathological analyses, different material processing approaches and molecular pathological tests are discussed, and novel concepts and strategies are lined out in order to improve the quality and reliability of the respective diagnostic procedures. RESULTS AND DISCUSSION: Predictive analyses of cytological specimens can be reliably performed using smears, cytospins or cell blocks; there is no need for histological specimens. The diagnostic work-up of cytological probes should be performed as carefully as possible in order to save further tumor material for subsequent predictive analyses. With standardized and reliable procedures at hand cytopathology is an important contribution to the multidisciplinary, complex care, and treatment of lung cancer patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Patologia Molecular/normas , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais/genética , Biópsia/métodos , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Comportamento Cooperativo , Receptores ErbB/genética , Humanos , Comunicação Interdisciplinar , Pulmão/patologia , Mutação/genética , Medicina de Precisão , Valor Preditivo dos Testes , Prognóstico , Receptores Proteína Tirosina Quinases/genética , Translocação GenéticaRESUMO
The anaplastic lymphoma kinase (ALK) can act as a key oncogenic driver after activation by means of processes such as gene rearrangement. In approximately 5 % of patients with advanced non-small cell lung cancer (NSCLC), an oncogenic fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and ALK has been detected using fluorescence in situ hybridisation (FISH). Moreover, various methods including immunohistochemistry and PCR-based assays can be used for analysing ALK expression. Clinical data have been generated for crizotinib, a small molecule inhibitor of the ALK receptor tyrosine kinase, demonstrating a substantial improvement of objective response rate and prolonged progression-free survival (PFS) compared to standard chemotherapy in pretreated NSCLC patients harbouring EML4-ALK fusion genes. In the current review, recent data on the detection and inhibition of ALK in advanced NSCLC are summarised.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/metabolismo , Quinase do Linfoma Anaplásico , Animais , Crizotinibe , Medicina Baseada em Evidências , Humanos , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Resultado do TratamentoRESUMO
Personalised medicine is becoming the standard care for advanced non-small cell lung cancer. Tumour-specific therapies based on biomarker analyses, e. g., EGFR mutations or translocations of the ALK gene locus, result in a superior patient outcome compared to unselected therapy approaches. However, predictive molecular analyses can be challenging and require significant experience with cell- and tissue-based diagnostic methods. The major challenge relates to the sometimes low amount of available tumour material for both diagnostic and predictive analyses. As yet, there are no standardised or evidence-based recommendations concerning biopsies, specimen processing, and analyses. Respective guidelines require combined interdisciplinary actions to consider both clinical and pathological aspects. In order to establish a basis for high quality procedures, different approaches, methods, and protocols were interdisciplinary discussed with an emphasis on cytological specimens. Detailed evaluation of the parameters and consented recommendations might contribute to optimised strategies in the interdisciplinary, more and more complex care of non-small cell lung cancer patients.