Asunto(s)
Transformación Celular Neoplásica , Sarcoma Histiocítico/patología , Linfoma Folicular/patología , Células Madre Neoplásicas/patología , Anciano , Femenino , Reordenamiento Génico , Sarcoma Histiocítico/genética , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma Folicular/genéticaRESUMEN
In this study, we investigated whether recurrences of classical Hodgkin's lymphoma (HL) are true relapses arising from the primary tumour or clonally unrelated secondary neoplasias. Formalin-fixed, paraffin-embedded tissue specimens of eleven patients with recurrent HL were analyzed. Hodgkin and Reed-Sternberg cells were microdissected after immunohistochemical staining for CD30 using laser-capture technique. Immunoglobulin heavy chain (IgH) gene fragment lengths were analyzed applying consensus FR3 and J primers. Two early relapses after the first HL diagnosis were clonally related to the initial tumour, while three of four early recurrences after a first or second relapse were not. Three patients presenting with late relapses had clonally unrelated neoplasms. Therefore, we conclude that recurrent HL may represent a novel neoplasm, a finding which might play a role in clinical decision-making.
Asunto(s)
Células Clonales/patología , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/patología , Cadenas Pesadas de Inmunoglobulina/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Regulación Neoplásica de la Expresión Génica/genética , Herpesvirus Humano 4/genética , Humanos , Células de Reed-Sternberg/patologíaRESUMEN
BACKGROUND: Some patients with non-small cell lung cancer (NSCLC) respond well to therapy with tyrosine kinase inhibitors (TKI). Somatic mutation of the epidermal growth factor receptor (EGFR) gene is an important predictive marker for TKI response. PATIENTS AND METHODS: We performed EGFR mutation analysis in 307 NSCLC (exon 18-21). The data were analyzed for associations with clinical-pathological parameters. RESULTS: Relevant EGFR mutations were found in 25/307 NSCLC (8.1%; 178 biopsies and 129 cytologies). Most mutations were found in exon 19 (50%) followed by the L858R point mutation in exon 21 (12.5%). EGFR mutations were significantly more common in women than in men (16.8% vs. 2.7%; p<0.001) and in adenocarcinoma than in other carcinoma subtypes (11.4% vs. 3.8%; p=0.017). EGFR mutation was associated with TTF-1 positivity (p<0.041). Almost all (96%) mutated NSCLC were TTF-1 positive. CONCLUSION: In Central Europe, the prevalence of relevant EGFR mutations in NSCLC is <10% of patients with NSCLC. EGFR mutations are more common in women and TTF-1 positive adenocarcinomas. Mutation analysis can be performed both from biopsies and cytologies.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Análisis Mutacional de ADN , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Biopsia , Deleción Cromosómica , Proteínas de Unión al ADN/genética , Diseño de Equipo , Exones/genética , Femenino , Humanos , Inmunohistoquímica , Pulmón/patología , Masculino , Microdisección/instrumentación , Microscopía Confocal/instrumentación , Mutación Puntual/genética , Reacción en Cadena de la Polimerasa , Pronóstico , Factores Sexuales , Factores de TranscripciónRESUMEN
Epidermal growth factor receptor (EGFR) gene mutations and increased copy numbers are considered as predictors of response to EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC). Lung cancer diagnosis is often based on cytology alone. However, almost all published data on EGFR gene analyses were obtained from biopsies. This study tested the feasibility of EGFR gene analyses on cytological specimens. Eighty-four cytological specimens from NSCLCs were prospectively analysed for EGFR gene mutation in exons 18-21 and EGFR gene copy numbers were evaluated by fluorescence in situ hybridisation (FISH). A FISH-positive result was defined according to the criteria by Cappuzzo et al established for biopsies of NSCLCs. Fluorescence in situ hybridisation results of cytological specimens were compared to the FISH results on matching biopsies (n=33). Initial diagnosis of NSCLC was solely based on cytology in 37 out of 84 (44.0%) patients. Out of 80 NSCLCs, 6 (7.5%) showed EGFR gene mutations. Out of 67 cancers, 45 (67.2%) were FISH positive on cytological specimens. Comparison of FISH showed a FISH-positive result in 21 out of 33 (63.6%) cytological specimens but in only 8 out of 33 (24.2%) matched biopsies. Epidermal growth factor receptor gene analyses are well applicable to cytological specimens. The high FISH-positive rate of NSCLC on cytological specimens contrasts with the low rate on biopsies when previously suggested criteria are used. New criteria for a positive EGFR FISH status to predict response to therapy with EGFR-TKI need to be defined for cytological specimens.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutación/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Biopsia , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/secundario , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Receptores ErbB/metabolismo , Exones/genética , Estudios de Factibilidad , Femenino , Dosificación de Gen , Humanos , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Tumores Neuroectodérmicos/genética , Tumores Neuroectodérmicos/metabolismo , Tumores Neuroectodérmicos/secundario , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
Current polymerase chain reaction (PCR) methods for the molecular diagnosis of B- and T-cell lymphomas by determination of clonality of immunoglobulin heavy chain (IgH) and T-cell receptor-gamma rearrangements and by detection of the chromosomal translocations t(14;18) and t(11;14), require several laborious and costly PCR assays for each of these diagnostic tests. We have developed a multiplex PCR assay for the simultaneous determination of B- and T-cell clonality and the detection of the chromosomal translocations t(14;18) and t(11;14) in a single reaction, using four-color fluorescence and automated high-resolution fragment analysis. The 26 primers combined in the multiplex PCR correspond to the sequences of >90% of the 69 variables and 6 join IgH genes and 100% of the T-cell receptor-gamma variables and join genes that could participate in the respective rearrangements. In addition, they detect the major and the minor breakpoint regions of the t(14;18) and the major breakpoint region of the t(11;14), and amplify the beta-globin gene as an internal control. The specificity of the multiplex PCR was confirmed by analysis of 39 T-cell lymphomas and 58 B-cell lymphomas, including 11 mantle cell lymphomas bearing the t(11;14) and 25 follicular lymphomas bearing the t(14;18), with known rearrangements and/or translocations. Fifteen samples of reactive lymphadenitis remained negative.