RESUMEN
BACKGROUND: Over the past few years, immune checkpoint inhibitors have changed the therapeutic landscape of non-small-cell lung cancer (NSCLC). Response to immune checkpoint inhibitors correlates with a pre-existing anti-tumoral immune response. Checkpoint inhibitors have been introduced as second-line therapy and are only very recently used as monotherapy or in combination with chemotherapy as first-line treatment of NSCLC. However, the effect of conventional first-line platinum-based chemotherapy on the immune infiltrate in the tumor is largely unknown. METHODS: We measured the gene expression of a custom set of 201 cancer- and immune-related genes in 100 NSCLC tumor biopsies collected before chemotherapy and 33 re-biopsies after platinum-based chemotherapy at the time point of progression. For 29 patients matched pre- and post-chemotherapy samples could be evaluated. RESULTS: We identified a cluster of 47 co-expressed immune genes, including PDCD1 (PD1) and CD274 (PD-L1), along with three other co-expression clusters. Chemotherapy decreased the average gene expression of the immune cluster while no effect was observed on the other three cluster. Within this immune cluster, CTLA4, LAG3, TNFRSF18, CD80 and FOXP3 were found to be significantly decreased in patient-matched samples after chemotherapy. CONCLUSION: Our results suggest that conventional platinum-based chemotherapy negatively impacts the immune microenvironment at the time point of secondary progression.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Expresión Génica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Microambiente Tumoral/genética , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , MasculinoRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico/biosíntesis , Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex/métodos , Estadificación de Neoplasias , Prevalencia , Supervivencia sin Progresión , Proteínas Proto-Oncogénicas c-met/biosíntesis , Proteínas Proto-Oncogénicas c-met/genética , Fumar/genética , Adulto JovenRESUMEN
A uniform classification system for reporting urinary cytology has not been available until recently, although urinary cytology represents an important volume of specimens in cytopathology laboratories and is well-established in the diagnosis and follow-up of patients with urothelial carcinoma. The Paris system is the first internationally accepted classification system, which allows uniform reporting of urinary cytology based on standardized morphological criteria. It emphasizes the detection of potentially life-threatening high-grade urothelial carcinomas and well-defined diagnostic categories have been developed. Notably, it aims at reducing the diagnosis of equivocal atypia and additionally at confining indications for a rational use of ancillary molecular techniques. The Paris system has already gained broad acceptance both in the cytology and urology communities, and promises to enhance the value of diagnostic urinary cytology.
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Carcinoma de Células Transicionales/patología , Biología Celular/clasificación , Neoplasias de la Vejiga Urinaria/patología , Orina/citología , Documentación/métodos , Humanos , Hibridación in Situ , Clasificación del Tumor , Prueba de Papanicolaou , Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote Tcell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. AIM: Practice-oriented review of the diagnosis and classification of irAEs. MATERIALS AND METHODS: Structured, selective literature review based on PubMed und UpToDate ® online. RESULTS: The most common irAEs affect the skin, the gastrointestinal tract, the liver, and the respiratory system. The correct diagnosis and classification of irAEs by an interdisciplinary care team is essential for appropriate therapy and the prevention of long-term sequelae. Other important irAEs affect the endocrine organs, the heart, the joints, the kidneys and the nervous system. Because of their rarity and/or limited options for bioptic diagnosis, only limited data on the morphology and pathophysiology of these irAEs are currently available. Autopsies carried out after ICI therapy constitute an important element of quality control and allow better documentation of the incidence and pathogenesis of irAEs. DISCUSSION: Pathology plays a central role in the diagnosis and treatment of irAEs. Future studies may contribute to a better mechanistic understanding of irAEs for individualized knowledge-based risk assessment.
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Anticuerpos Monoclonales/efectos adversos , Factores Inmunológicos/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/patología , Neoplasias/terapia , HumanosRESUMEN
Using tritium-labeled thymidine histoautoradiography, the AgNOR staining technique and Ki67-MIB-1 immunohistochemistry to study cell kinetics, prostate cancer can be subdivided into slowly, moderately and rapidly proliferating tumors. These are important supplementary methods and prerequisites for a grading as low, intermediate and high-grade in addition to classical histology and cytology. Cytometry of DNA can confirm the cell kinetics of prostate cancer by detection of a predominance of diploid or aneuploid cell nuclei but should only be evaluated together with histological investigations. All histology-based analyses of cell kinetics encompass the classical highly and poorly differentiated glandular and cribriform patterns as well as solid undifferentiated structures and the various subcategories. The malignancy grading of prostate cancer can result from the summation of histological grading and cell kinetic analyses, as long as the named investigations are included. The future perspectives of individualized therapy options, including active surveillance in early low-grade and also for high-grade prostate cancer and new antihormonal treatment in advanced disease, may increasingly rely on tissue biomarkers and advanced technologies for whole genome analysis including next generation sequencing.
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Transformación Celular Neoplásica/patología , Neoplasias de la Próstata/patología , Autorradiografía , Proliferación Celular , Transformación Celular Neoplásica/genética , ADN de Neoplasias/genética , Humanos , Citometría de Imagen , Inmunohistoquímica , Masculino , Clasificación del Tumor , Medicina de Precisión , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapiaRESUMEN
The continued development of methods in needle biopsies and radical prostatectomy for treatment of prostate cancer has given special emphasis to the question of the prognostic relevance of the various systems of grading. The classical purely histological grading system of Gleason has been modified several times in the past decades and cleared the way for a new grading system by the prognostic grading of Epstein. Assessment of the old and also modified combined histological and cytological grading of Mostofi, the World health Organization (WHO) and the urologic-pathological working group of prostate cancer in connection with the Gleason grading (combined Gleason-Helpap grading), has led to considerably improved rates of concordance between biopsy and radical prostatectomy and to improved estimations of prognosis beside its contribution to the development of a more practicable grading system for clinical use.
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Clasificación del Tumor/métodos , Neoplasias de la Próstata/patología , Sociedades Médicas , Predicción , Humanos , Masculino , Clasificación del Tumor/tendencias , Próstata/patologíaRESUMEN
Personalized therapy concepts in which the active agent is adapted to genetic alterations in the tumor of the patient, have in recent years led to a paradigm shift in oncology. A comprehensive molecular diagnostic tumor characterization is therefore essential before initiating therapy in order to select the optimal therapy for the patient. The continuously increasing number of genetic alterations which can be treated and known resistance mechanisms together with limited availability of test material represents a completely new challenge for molecular diagnostics. The possibility of being able to determine mutations, translocations and changes in the number of copies not only from paraffin-embedded tumor tissue but also from cytological material and even circulating tumor DNA, substantially extends the diagnostic options.
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Análisis Citogenético/métodos , Neoplasias/genética , Neoplasias/patología , Patología Molecular/métodos , Medicina de Precisión , Biomarcadores de Tumor/genética , Marcadores Genéticos/genética , Neoplasias/terapia , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC. METHODS: FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I-II. The FISH results were correlated with clinico-pathological features and overall survival (OS). RESULTS: The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC. CONCLUSIONS: FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/genética , Amplificación de Genes , Neoplasias Pulmonares/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Análisis de Matrices TisularesRESUMEN
To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.
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Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/patología , Técnicas de Diagnóstico Molecular/métodos , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
BACKGROUND: Detection of fungal DNA from formalin-fixed, paraffin-embedded (FFPE) tissue is challenging due to degradation of DNA and presence of PCR inhibitors in these samples. We analyzed FFPE samples of 26 patients by panfungal PCR and compared the results to the composite diagnosis according to the European Organization for Research and Treatment of Cancer (EORTC) criteria. Additionally we analyzed the quality of human and fungal DNA and their level of age-dependent degradation, as well as the existence of PCR inhibition in these tissue samples. METHODS: We evaluated two 45-cycle panfungal PCR tests that target the internal transcribed spacer 2 (ITS2) as well as the ITS1-5.8S-ITS2 (ITS1-2) region. The PCRs were applied to 27 FFPE specimens from 26 patients with proven invasive fungal disease (IFD), and one patient with culture and histologically negative but PCR-positive fungal infection collected at our institution from 2003 to 2010. Quality of DNA in FFPE tissue samples was evaluated using fragments of the beta-globin gene for multiplex PCR, inhibition of PCR amplification was evaluated by spiking of C. krusei DNA to each PCR premix. RESULTS: In 27 FFPE samples the ITS2 PCR targeting the shorter fragment showed a higher detection rate with a sensitivity of 53.8% compared to the ITS1-2 fragment (sensitivity 38%). Significant time-dependent degradation of human DNA in FFPE sample extracts was detected based on partial beta-globin gene amplification which was not in correlation to successful panfungal PCR identification of fungal organisms. The analytical sensitivity of both assays compared with culture was 60 CFU/ml of a Candida krusei reference strain. The performance of the two tests in an Aspergillus proficiency panel of an international external quality assessment programme showed considerable sensitivity. CONCLUSION: Panfungal diagnostic PCR assays applied on FFPE specimens provide accurate identification of molds in highly degraded tissue samples and correct identification in samples stored up to 7 years despite sensitivity limitations, mainly caused by partial PCR inhibition and DNA degradation by formalin.
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Aspergilosis/diagnóstico , ADN de Hongos/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Aspergilosis/microbiología , Aspergillus/genética , ADN de Hongos/genética , Fijadores/química , Formaldehído/química , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Tipificación Micológica , Adhesión en Parafina , Sensibilidad y Especificidad , Fijación del TejidoRESUMEN
The definitive diagnosis of malignant mesothelioma (MM) in effusion cytology is often avoided or reluctantly made by cytology alone. The most probable reason for this skepticism is the lack of expertise in cytology among many pathologists and clinicians. When an effusion specimen is composed of cells with unequivocal cytological features of malignancy that have the morphology and immunophenotype of mesothelial cells, the cytological diagnosis of MM is straightforward. However, in the daily routine difficult cases of atypical mesothelial cells are often encountered and additional methods are required to establish an accurate diagnosis. In contrast to reactive mesothelial cells cells of MMs often harbor chromosomal aberrations, most frequently a polysomy in combination with a 9p21 deletion. These chromosomal aberrations can easily be detected by multitarget fluorescence in situ hybridization (FISH); therefore, FISH allows a reliable distinction between reactive mesothelial cells and MM cells. In order to be able to discriminate between MM and adenocarcinoma, an immunocytochemical panel consisting of different mesothelial and epithelial markers is very helpful. In most inconclusive cases of atypical mesothelial cells the combination of morphology, immunocytochemistry and FISH allows a better distinction between reactive mesothelial cells and MM in effusion cytology.
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Mesotelioma/genética , Mesotelioma/patología , Técnicas de Diagnóstico Molecular , Neoplasias Pleurales/genética , Neoplasias Pleurales/patología , Diagnóstico Diferencial , Humanos , Pulmón/patología , Mesotelioma/clasificación , Invasividad Neoplásica , Pleura/patología , Neoplasias Pleurales/clasificación , Organización Mundial de la SaludRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Patología Molecular/normas , Quinasa de Linfoma Anaplásico , Biomarcadores de Tumor/genética , Biopsia/métodos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Terapia Combinada , Conducta Cooperativa , Receptores ErbB/genética , Humanos , Comunicación Interdisciplinaria , Pulmón/patología , Mutación/genética , Medicina de Precisión , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Tirosina Quinasas Receptoras/genética , Translocación GenéticaRESUMEN
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.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Marcadores Genéticos/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Técnicas de Diagnóstico Molecular/métodos , Medicina de Precisión/métodos , HumanosRESUMEN
BACKGROUND: The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression. PATIENTS AND METHODS: We assessed PD-L1 expression by immunohistochemistry (Ventana SP263 assay) on tumor cells in treatment-naive diagnostic tumor samples and matched lung resections from patients with stage III non-small-cell lung cancer included in the Swiss Group for Clinical Cancer Research (SAKK) trials 16/96, 16/00, 16/01, and 16/14. All patients received neoadjuvant chemotherapy (CT) with cisplatin/docetaxel, either as single modality (CT), with sequential radiotherapy [chemoradiation therapy (CRT)] or with the PD-L1 inhibitor durvalumab (CT + ICI). RESULTS: Overall, 132 paired tumor samples were analyzed from patients with neoadjuvant CT (n = 69), CRT (n = 33) and CT + ICI (n = 30). For CT and CRT, PD-L1 expression before and after neoadjuvant treatment did not differ significantly (Wilcoxon test, P = 0.94). Likewise, no statistically significant difference was observed between CT and CRT for PD-L1 expression after neoadjuvant treatment (P = 0.97). For CT + ICI, PD-L1 expression before and after neoadjuvant treatment also did not differ significantly (Wilcoxon test, P > 0.99). Event-free survival and overall survival for patients with downregulation or upregulation of PD-L1 expression after neoadjuvant treatment were similar. CONCLUSIONS: In our cohort of patients neoadjuvant treatment did not influence PD-L1 expression, irrespective of the specific neoadjuvant treatment protocol. Dynamic change of PD-L1 expression did not correlate with event-free survival or overall survival.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Terapia Neoadyuvante , Antígeno B7-H1 , Neoplasias Pulmonares/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. METHODS: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). RESULTS: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473 days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8). CONCLUSIONS: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/etiología , Infecciones del Sistema Respiratorio/etiología , Adulto , Antivirales/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Huésped Inmunocomprometido , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Persona de Mediana Edad , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/tratamiento farmacológico , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ribavirina/uso terapéutico , Tomografía Computarizada por Rayos X , Trasplante HomólogoRESUMEN
The diagnosis and treatment of non-small cell lung cancer (NSCLC) have been revolutionized over the last few years. Requirements for cytopathologists in lung cancer diagnosis have therefore changed. The general diagnostic category of NSLC is no longer sufficient. In addition cytological specimens need to be evaluated for adequacy regarding predictive marker analyses. Accurate NSCLC subtyping with a distinction of adenocarcinoma from squamous cell carcinoma is crucial for treatment decisions as the subtype will decide on the chemotherapy regimen and the choice of predictive marker analyses for targeted treatment. In the majority of cases, the subtype can be diagnosed by morphology alone. Cytology is equally well suited as biopsy specimens for the assessment of molecular predictive markers. The best results are achieved when both cytology and biopsy specimens are compared to choose the most appropriate specimen for morphological subtyping and molecular testing. In this paper, we discuss special issues of NSCLC subtyping and currently recommended predictive molecular marker analyses.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Biología Celular , Marcadores Genéticos/genética , Neoplasias Pulmonares/patología , Adenocarcinoma/clasificación , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patología , Algoritmos , Antineoplásicos/uso terapéutico , Biopsia , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/clasificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Análisis Mutacional de ADN , Receptores ErbB/genética , Humanos , Inmunohistoquímica/métodos , Pulmón/patología , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Estadificación de Neoplasias , Proteínas de Fusión Oncogénica/genética , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Resultado del Tratamiento , Proteínas ras/genéticaAsunto(s)
Extracción de Catarata , Catarata , Cuerpos Extraños , Facoemulsificación , Cámara Anterior , Cefuroxima , Cuerpos Extraños/diagnóstico , HumanosRESUMEN
Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. New techniques, such as serial analysis of gene expression and cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. These genome screening tools can comprehensively survey one tumor at a time; however, analysis of hundreds of specimens from patients in different stages of disease is needed to establish the diagnostic, prognostic and therapeutic importance of each of the emerging cancer gene candidates. Here we have developed an array-based high-throughput technique that facilitates gene expression and copy number surveys of very large numbers of tumors. As many as 1000 cylindrical tissue biopsies from individual tumors can be distributed in a single tumor tissue microarray. Sections of the microarray provide targets for parallel in situ detection of DNA, RNA and protein targets in each specimen on the array, and consecutive sections allow the rapid analysis of hundreds of molecular markers in the same set of specimens. Our detection of six gene amplifications as well as p53 and estrogen receptor expression in breast cancer demonstrates the power of this technique for defining new subgroups of tumors.
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Neoplasias de la Mama/genética , Técnicas Genéticas , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ciclina D1/genética , Ciclina D1/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Ratones , Proteínas Oncogénicas v-myb , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Conejos , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Proteínas Oncogénicas de Retroviridae/genética , Proteínas Oncogénicas de Retroviridae/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The World Health Organization (WHO) 2004 classification includes 3 categories of pulmonary preneoplastic lesions, including squamous dysplasia and carcinoma in situ (CIS) for squamous cell carcinoma, atypical adenomatous hyperplasia (AAH) for the majority of adenocarcinomas and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) for carcinoids. The distinction of the 3 grades of squamous dysplasia and CIS is mainly based on the degree by which the basal cell zone is expanded, the degree of cellular atypia and the level of mitoses. The category AAH consists of a proliferation of atypical epithelial cells with Clara cells or type 2 pneumocyte features. They grow along the alveolar septae in a lepidic fashion, sometimes reaching into the terminal bronchioles. In contrast to the newly described adenocarcinoma in situ (AIS), AAH is smaller (≤ 5 mm), has a lower cell density and a lower degree of cellular atypia. The putative cancer stem cells of peripheral adenocarcinomas reside in the bronchioloalveolar duct junction, while those of central squamous cell carcinomas are located in the basal cell compartment of the bronchi. This review provides an overview of the current knowledge on preneoplastic lesions of the lungs and their clinical impact.
Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/patología , Adenomatosis Pulmonar/genética , Adenomatosis Pulmonar/patología , Tumor Carcinoide/genética , Tumor Carcinoide/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Proliferación Celular , Humanos , Hiperplasia , Pulmón/patología , Índice MitóticoRESUMEN
BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.