The use of P63 immunohistochemistry for the identification of squamous cell carcinoma of the lung.

INTRODUCTION: While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of "carcinoma NOS (not otherwise specified)" in a prospective series of small tumor samples. METHODS: With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC. RESULTS: The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs. CONCLUSIONS: P63 IHC is useful for the identification of lung SCCs.

Pronóstico tras una agudización grave de la EPOC tratada con ventilación mecánica no invasiva / Prognosis Following Acute Exacerbation of COPD Treated With Non-invasive Mechanical Ventilation

IntroducciónLos pacientes con EPOC que sobreviven a una exacerbación grave que necesita ventilación mecánica no invasiva son un grupo de mal pronóstico.ObjetivoConocer las tasas de reingreso y mortalidad durante el año siguiente a su alta y analizar los factores asociados a ambos desenlaces.MétodosUna cohorte de 93 pacientes con EPOC, que sobrevivieron a una exacerbación de la EPOC que precisó ventilación mecánica no invasiva, fue seguida tras el alta. Se midieron la necesidad de hospitalización por motivos respiratorios y la supervivencia, y se analizaron frente a posibles factores asociados a esos eventos mediante una regresión multivariante de riesgos proporcionales de Cox.ResultadosDurante el año siguiente al alta, 61 pacientes (66%) precisaron una nueva hospitalización. En el análisis multivariante, un valor bajo de FEV1 y una elevada estancia media durante la hospitalización se asociaron de forma independiente con un elevado riesgo de reingreso hospitalario. La probabilidad de supervivencia al año fue de 0,695 (IC95%: 0,589–0,778). En el análisis multivariante la edad, la PaCO2 antes de iniciar la ventilación mecánica no invasiva y los días de hospitalización en el año previo se asociaron de forma independiente con un elevado riesgo de mortalidad.ConclusionesEste grupo de pacientes con EPOC presenta una alta mortalidad y necesidad de rehospitalización en el año siguiente al alta. Las variables estudiadas relacionadas con la gravedad de la enfermedad de base y de la propia agudización demostraron estar asociadas a esos eventos y podrían utilizarse para la aplicación en este subgrupo de pacientes de programas específicos de seguimiento(AU)

IntroductionPatients with chronic obstructive pulmonary disease (COPD) who survived an acute exacerbation with acute respiratory failure that required non-invasive mechanical ventilation (NIMV) are a group with a poor medium-term prognosis.ObjectiveTo identify re-admission and mortality rates within one year from discharge and to analyse factors associated with both events in a consecutive series of COPD patients treated with NIMV.MethodsA cohort of 93 COPD patients who survived an acute exacerbation and who required NIMV was followed up after discharge. Re-admissions due to respiratory causes and survival were measured and the outcomes were analysed against possible factors associated to such events using multivariate Cox proportional risk regression analysis.ResultsOver the year following discharge, 61 patients (66%) had to be re-admitted into hospital due to respiratory complications. Upon multivariate analysis, a low FEV1 value in stable phase and a high average length of stay were associated independently with a high risk of hospital readmission. The probability of survival at 1 year was 0.695. Age, PaCO2 prior to initiation of NIMV and the number of hospitalisation days in the previous year were associated independently with a high mortality risk.ConclusionsThis group of COPD patients has a high mortality rate and need for re-hospitalisation in the ensuing year following discharge. The variables relating to the severity of the baseline disease and the actual exacerbation have been shown to be associated with these events, and could be applied to this subgroup of patients in specific follow-up programs(AU)

[Prognosis following acute exacerbation of COPD treated with non-invasive mechanical ventilation]. / Pronóstico tras una agudización grave de la EPOC tratada con ventilación mecánica no invasiva.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) who survived an acute exacerbation with acute respiratory failure that required non-invasive mechanical ventilation (NIMV) are a group with a poor medium-term prognosis. OBJECTIVE: To identify re-admission and mortality rates within one year from discharge and to analyse factors associated with both events in a consecutive series of COPD patients treated with NIMV. METHODS: A cohort of 93 COPD patients who survived an acute exacerbation and who required NIMV was followed up after discharge. Re-admissions due to respiratory causes and survival were measured and the outcomes were analysed against possible factors associated to such events using multivariate Cox proportional risk regression analysis. RESULTS: Over the year following discharge, 61 patients (66%) had to be re-admitted into hospital due to respiratory complications. Upon multivariate analysis, a low FEV(1) value in stable phase and a high average length of stay were associated independently with a high risk of hospital readmission. The probability of survival at 1 year was 0.695. Age, PaCO(2) prior to initiation of NIMV and the number of hospitalisation days in the previous year were associated independently with a high mortality risk. CONCLUSIONS: This group of COPD patients has a high mortality rate and need for re-hospitalisation in the ensuing year following discharge. The variables relating to the severity of the baseline disease and the actual exacerbation have been shown to be associated with these events, and could be applied to this subgroup of patients in specific follow-up programs.

Utilidad de la tomografía por emisión de positrones en la detección de metástasis ocultas extratorácicas en el carcinoma broncogénico no células pequeñas / Use of Positron Emission Tomography in Assessing Hidden Extrathoracic Metastasis in Non Small Cell Lung Cancer

IntroducciónLa tomografía de emisión de positrones asociada a la tomografía axial computerizada (PET/TC) se utiliza en la estadificación del carcinoma broncogénico no microcítico (CBNM). El objetivo de este trabajo es describir la utilidad de la PET/TC en la estadificación clínica del CBNM para la detección de metástasis extratorácicas insospechadas en una población operable con un tumor aparentemente resecable antes de la evaluación ganglionar mediastínica pretoracotomía.Pacientes y métodoEstudio prospectivo y concurrente de todos los casos de CBNM recogidos entre junio 2004 y noviembre 2006, a los que se realizo una PET/TC tras considerar al paciente operable y al tumor resecable tras realizar broncoscopia, TC toracoabdominal, y TC cerebral o gammagrafía ósea si hubiesen datos clínicos sugerentes de metástasis a esos niveles. La metástasis fueron confirmadas por evidencia citohistológica o por la evolución.ResultadosSe realizó una PET/TC a 91 pacientes con CBNM. En 24 pacientes (26%) se objetivo la existencia de, al menos, una captación extratorácica. En 7 pacientes (7,7%) la captación correspondió a una metástasis extratorácica del CBNM, oculta a la estadificacion convencional. En 3 casos (3,2%) la captación extratorácica correspondió a lesiones premalignas o a un segundo tumor primario. En 12 pacientes (13,1%) el hallazgo correspondía a lesiones benignas, y finalmente en 2 casos (2,2%) no se pudo determinar el origen de la captación.ConclusionesLa PET/TC indicada en pacientes operables con CBNM potencialmente resecables supone un elemento diagnóstico de utilidad en la detección de metástasis ocultas que afecta a la toma de decisiones terapéuticas(AU)

IntroductionPositron emission tomography combined with computed axial tomography (PET/CT) is used for staging non small cell lung cancer (NSCLC). This study aims to describe PET/CT findings of unsuspected extrathoracic metastasis when used in mediastinal evaluation of patients with apparently resectable NSCLC.Patients and methodProspective and concurrent study including all NSCLC patients between June 2004 and November 2006 who underwent PET/CT after considering them as candidates for surgery, with resectable disease after bronchoscopy, thorax and abdominal CT, brain CT and bone gammagraphy evaluation, if metastasis at these locations were suspected. Metastasis were confirmed histopathologically or assumed when they had a compatible evolution.ResultsA total of 91 patients with NSCLC underwent PET/CT. In 24 of them (26%) at least one suspicious extrathoracic uptake was seen. In 7 patients (7.7%) those uptakes were NSCLC extrathoracic metastasis hidden from conventional staging. In 3 of these cases (13.1%) extrathoracic uptakes corresponded to metacrhonous tumours or pre-malignant conditions. Benign lesions were found in 12 patients (13.1%), and in 2 cases (2.2%) the uptake origins were undetermined.ConclusionsPET/CT is a complementary diagnosis method for assessing hidden metastases which could modify the therapeutical approach in patients otherwise suitable for surgery(AU)

[Use of positron emission tomography in assessing hidden extrathoracic metastasis in non small cell lung cancer]. / Utilidad de la tomografía por emisión de positrones en la detección de metástasis ocultas extratorácicas en el carcinoma broncogénico no células pequeñas.

INTRODUCTION: Positron emission tomography combined with computed axial tomography (PET/CT) is used for staging non small cell lung cancer (NSCLC). This study aims to describe PET/CT findings of unsuspected extrathoracic metastasis when used in mediastinal evaluation of patients with apparently resectable NSCLC. PATIENTS AND METHOD: Prospective and concurrent study including all NSCLC patients between June 2004 and November 2006 who underwent PET/CT after considering them as candidates for surgery, with resectable disease after bronchoscopy, thorax and abdominal CT, brain CT and bone gammagraphy evaluation, if metastasis at these locations were suspected. Metastasis were confirmed histopathologically or assumed when they had a compatible evolution. RESULTS: A total of 91 patients with NSCLC underwent PET/CT. In 24 of them (26%) at least one suspicious extrathoracic uptake was seen. In 7 patients (7.7%) those uptakes were NSCLC extrathoracic metastasis hidden from conventional staging. In 3 of these cases (13.1%) extrathoracic uptakes corresponded to metacrhonous tumours or pre-malignant conditions. Benign lesions were found in 12 patients (13.1%), and in 2 cases (2.2%) the uptake origins were undetermined. CONCLUSIONS: PET/CT is a complementary diagnosis method for assessing hidden metastases which could modify the therapeutical approach in patients otherwise suitable for surgery.

[Prognostic value study of lung cancer molecular markers]. / Valor pronóstico de los marcadores moleculares en el carcinoma broncogénico.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine the prognostic value of molecular markers (proteins) of different paths of lung cancer development in patients with non small cell lung carcinoma (NSCLC) in initial stages. MATERIAL AND METHOD: Observational, cohort study in patients with NSCLC that was initially treated surgically in our hospital between October 1993 and September 1997. Thirty-two proteins were selected. The study consisted of the elaboration of tissue arrays with samples from resected tumour, using a semiquantitative immunohistochemical study. A prognosis analysis was done with the expression of each protein and calculation of the overall 5-year survival rate. The Wilcoxon-Gehan and Log-Rank tests were used for statistical comparisons, with p<.05 being considered to indicate a significant result. RESULTS: One hundred and forty six patients were studied. The overall 5-year survival rate was 37.7%. From 32 proteins studied, three were statistically associated with overall 5-year survival rate. RB protein expression in resected NSCLC was a positive prognostic factor (P=.01). P27 (P=.03) and Ki67 (P=.04) expression in resected NSCLC were negative prognostic factors. There was no protein with prognostic value in epidermoid tumours. CONCLUSIONS: We found three proteins with long-term prognostic value in the long-term in the general population and five adenocarcinoma prognostic proteins in our study of resected non-small cell lung cancer (NSCLC). In the future, genetic-molecular factors should be included along with anatomical (TNM staging) and clinical factors in a multidimensional lung cancer staging.

Valor pronóstico de los marcadores moleculares en el carcinoma broncogénico / Prognostic value study of lung cancer molecular markers

Fundamentos y objetivo: Estudio pronóstico de marcadores moleculares implicados en la carcinogénesis del carcinoma broncogénico (CB), en pacientes con CB no microcítico (CBNM) resecado en estadios iniciales. Material y método: Estudio observacional y de cohorte de pacientes con CBNM en estadios iniciales intervenidos en el Hospital 12 de Octubre de Madrid entre el 1 de octubre de 1993 y el 30 de septiembre de 1997. Se estudiaron 32 proteínas con un análisis inmunohistoquímico semicuantitativo. Se realizó un análisis de la expresión de cada proteína en relación con la supervivencia a 5 años mediante las pruebas de Wilcoxon-Gehan y log rank, aceptando como significativo un valor de p<0,05.ResultadosEl número final de pacientes incluidos fue de 146. La supervivencia a 5 años fue del 37,7%. De las 32 proteínas, hemos encontrado tres con significado pronóstico a 5 años: la expresión de RB, asociada a mejor pronóstico (p=0,01), y la expresión de p27 (p=0,03) y Ki67 (p=0,04), asociadas a peor pronóstico. En el análisis según histología no hay ninguna proteína con valor pronóstico en CB epidermoide, mientras que hay cinco en adenocarcinomas. Conclusiones: En esta serie de CBNM resecado hay 3 marcadores moleculares con valor pronóstico a largo plazo en la población general y cinco en adenocarcinomas. Probablemente, en el futuro los factores moleculares se unan a los de extensión anatómica y clínicos en una clasificación pronóstica multidimensional en CB (AU)

Background and objective: The aim of this study was to determine the prognostic value of molecular markers (proteins) of different paths of lung cancer development in patients with non small cell lung carcinoma (NSCLC) in initial stages. Material and method: Observational, cohort study in patients with NSCLC that was initially treated surgically in our hospital between October 1993 and September 1997. Thirty-two proteins were selected. The study consisted of the elaboration of tissue arrays with samples from resected tumour, using a semiquantitative immunohistochemical study. A prognosis analysis was done with the expression of each protein and calculation of the overall 5-year survival rate. The Wilcoxon-Gehan and Log-Rank tests were used for statistical comparisons, with p<.05 being considered to indicate a significant result. Results: One hundred and forty six patients were studied. The overall 5-year survival rate was 37.7%. From 32 proteins studied, three were statistically associated with overall 5-year survival rate. RB protein expression in resected NSCLC was a positive prognostic factor (P=.01). P27 (P=.03) and Ki67 (P=.04) expression in resected NSCLC were negative prognostic factors. There was no protein with prognostic value in epidermoid tumours. Conclusions: We found three proteins with long-term prognostic value in the long-term in the general population and five adenocarcinoma prognostic proteins in our study of resected non-small cell lung cancer (NSCLC). In the future, genetic-molecular factors should be included along with anatomical (TNM staging) and clinical factors in a multidimensional lung cancer staging (AU)

Analysis of the molecular expression profile of non small cell lung carcinoma associated to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor to develop lung cancer but there are no different functional clusters of biomarkers between patients with non-small cell lung cancer (NSCLC) with or without COPD. To analyse protein expression, in order to find out whether samples of resected NSCLC from patients with COPD present a different molecular expression. Observational, cohort, concurrent study with sampling since treatment of disease in patients with NSCLC in initial stages (pIA-pIIB) treated surgically in our hospital between October 1993 and September 1997. The study consisted of the elaboration of tissue arrays with samples from resected tumor, using immunohistochemistry as a study method. Univariate analysis and logistic regression analysis were performed in order to determine molecular markers that showed a differential expression in NSCLC of the patients with COPD. We studied thirty-two proteins in 146 patients. 30% of the patients had COPD. Univariate analysis in patients with COPD showed one molecular marker to be overexpressed and five molecular markers to be underexpressed. Multivariate analysis in patients with COPD identified membranous beta-Catenin as a differential biomarker, which displayed an underexpression, with an Odds Ratio (95% Confidence Interval) of 0.26 (0.07-1.01). A significant lowest expression of membranous beta-catenin was detected in NSCLC of the patients with COPD.

[Bronchogenic carcinoma 2000-2001: characteristics and overall survival]. / Carcinoma broncogénico 2000-2001: características y supervivencia global.

OBJECTIVE: To describe the clinical characteristics and survival of patients diagnosed with bronchogenic carcinoma during the years 2000 and 2001 in a tertiary level hospital. PATIENTS AND METHODS: Data were collected from our hospital's tumor registry and validated with independent sources. Of all the patients diagnosed with or treated for bronchogenic carcinoma in our hospital, only those from our health care area were selected. RESULTS: During the 2-year study period, 482 patients were diagnosed. Of those, 91% were men. The mean (SD) age was 66.6 (9.65) years. Large cell carcinomas accounted for 29.4% of cases. Of all the cases of bronchogenic carcinoma, 41.3% were diagnosed in stage IV. Thirty percent of non-small cell carcinomas were classified as stage I, compared to 6% of small cell carcinomas (P< .001). The most frequent treatment was chemotherapy (42.1%) and 20% of patients underwent surgery. The overall 5-year survival rate was 13% (95% confidence interval [CI], 10%-16%), while survival was significantly lower in patients aged 68 years or older (95% CI, 3%-15%; P< .001) and in patients with small cell carcinoma (0%, P< .01). CONCLUSIONS: Our recent experience (2000-2001) confirmed the advanced age of patients with bronchogenic carcinoma, the frequency of diagnosis in advanced stages of the disease (41% in stage IV), and the low overall 5-year survival rate (13%).

Carcinoma broncogénico 2000-2001: características y supervivencia global / Bronchogenic carcinoma 2000-2001: characteristics and overall survival

Objetivo: Describir las características clínicas y la supervivencia de los carcinomas broncogénicos (CB) diagnosticados durante los años 2000 y 2001 en un hospital terciario. Pacientes y métodos: La información se recogió de la base de datos del Registro de Tumores del hospital y se validó con fuentes independientes. De todos los pacientes con CB diagnosticados o tratados en nuestro centro, se seleccionó a los que provenían exclusivamente del área de salud correspondiente. Resultados: Se diagnosticaron 482 casos en los 2 años del estudio; un 90% de los pacientes eran varones. La edad media ± desviación estándar fue de 66,6 ± 9,65 años. El 29,4% eran CB de células grandes. El 41,3% de todos los CB se diagnosticaron en estadio IV. El 30% de los CB no microcíticos se clasificaron en estadio I, en comparación con el 6% de los CB microcíticos (p < 0,001). El tratamiento más frecuente fue la quimioterapia (42,1%); la cirugía se efectuó en el 20% de los casos. La supervivencia global a los 5 años fue de 13% (intervalo de confianza del 95%, 10-16%), y fue significativamente inferior (p < 0,001) en los pacientes con mayor edad (≥ 68 años), en quienes se cifró en un 9% (intervalo de confianza del 95%, 3-15), y en el CB microcítico (0%; p < 0,01). Conclusiones: Se confirma en nuestra reciente experiencia (2000-2001) la elevada edad de los pacientes con CB, el frecuente diagnóstico en estadios avanzados (estadio IV: 41%) y la deficiente supervivencia global a los 5 años (el 13% del global)

Objective: To describe the clinical characteristics and survival of patients diagnosed with bronchogenic carcinoma during the years 2000 and 2001 in a tertiary level hospital. Patients and Methods: Data were collected from our hospital´s tumor registry and validated with independent sources. Of all the patients diagnosed with or treated for bronchogenic carcinoma in our hospital, only those from our health care area were selected. Results: During the 2-year study period, 482 patients were diagnosed. Of those, 91% were men. The mean (SD) age was 66.6 (9.65) years. Large cell carcinomas accounted for 29.4% of cases. Of all the cases of bronchogenic carcinoma, 41.3% were diagnosed in stage IV. Thirty percent of non-small cell carcinomas were classified as stage I, compared to 6% of small cell carcinomas (P<.001). The most frequent treatment was chemotherapy (42.1%) and 20% of patients underwent surgery. The overall 5-year survival rate was 13% (95% confidence interval [CI], 10%-16%), while survival was significantly lower in patients aged 68 years or older (95% CI, 3%-15%; P<.001) and in patients with small cell carcinoma (0%, P<.01). Conclusions: Our recent experience (2000-2001) confirmed the advanced age of patients with bronchogenic carcinoma, the frequency of diagnosis in advanced stages of the disease (41% in stage IV), and the low overall 5-year survival rate (13%)

Loss of the mitochondrial bioenergetic capacity underlies the glucose avidity of carcinomas.

The down-regulation of the catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is a hallmark of most human carcinomas. This characteristic of the cancer cell provides a proteomic signature of cellular bioenergetics that can predict the prognosis of colon, lung, and breast cancer patients. Here we show that the in vivo tumor glucose uptake of lung carcinomas, as assessed by positron emission tomography in 110 patients using 2-deoxy-2-[18F]fluoro-d-glucose as probe, inversely correlates with the bioenergetic signature determined by immunohistochemical analysis in tumor surgical specimens. Further, we show that inhibition of the activity of oxidative phosphorylation by incubation of cancer cells with oligomycin triggers a rapid increase in their rates of aerobic glycolysis. Moreover, we show that the cellular expression level of the beta-F1-ATPase protein of mitochondrial oxidative phosphorylation inversely correlates (P < 0.001) with the rates of aerobic glycolysis in cancer cells. The results highlight the relevance of the alteration of the bioenergetic function of mitochondria for glucose capture and consumption by aerobic glycolysis in carcinomas.

Alteration of the VRK1-p53 autoregulatory loop in human lung carcinomas.

Human VRK1 (vaccinia-related kinase 1) is a novel serine-threonine kinase that regulates several transcription factors, including p53, ATF2 and c-Jun; and its loss results in defects of cell proliferation. VRK1 stabilizes p53 and the accumulated p53 downregulates VRK1 forming an autoregulatory loop. Wild-type p53, but not mutant p53, was able to downregulate VRK1 in the A549 lung carcinoma cell line. VRK1 expression has been studied in human lung carcinomas. VRK1 protein level was significantly higher in squamous cell lung carcinomas than in adenocarcinomas, and inversely correlated with p16. Tumours with p53 mutations have a positive trend with those having very high levels of VRK1 protein, particularly in squamous cell lung carcinomas. These data indicate that the VRK1-p53 autoregulatory loop was not functional in a group of lung carcinomas. The accumulation of VRK1 in tumours with mutant p53 could result in stimulation of other signalling pathways that can contribute to tumour growth and progression in addition to those resulting from loss of p53 function.

Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein immunostaining in human normal tissues and lung carcinomas.

The LKB1 tumor suppressor gene codes for a serine/threonine protein kinase, and among its substrates is the adenosine monophosphate-dependent protein kinase, a sensor of intracellular energy levels. LKB1 is genetically inactivated in several types of tumors, especially lung adenocarcinomas. Here we used immunohistochemistry to evaluate the levels of LKB1 and the phosphorylated form of the acetyl-CoA carboxylase (ACC) protein in a variety of human adult normal tissues and in 159 lung carcinomas. The enzyme ACC becomes inactive upon phosphorylation by adenosine monophosphate-dependent protein kinase. Our analysis in normal tissues revealed strong LKB1 immunostaining in most epithelia, in the seminiferous tubules of the testis, in myocytes from skeletal muscle, and in glia cells. In contrast to the cytosolic location of LKB1 found in most tissues, glia cells carried mainly nuclear LKB1. Some epithelial cells showed apical accumulation of LKB1, supporting its role in cell polarity. Regarding phospho-ACC (p-ACC), strong immunostaining was observed in myocytes from the skeletal muscle and heart, and in Leydig cells of the testis. In lung tumors, LKB1 immunostaining was absent, moderate, and high in 20%, 61%, and 19% of the tumors, respectively, whereas p-ACC immunostaining was found to be absent/low, moderate, and high in 35%, 34%, and 31% of the tumors, respectively. High levels of LKB1 and p-ACC immunostaining predominated in lung adenocarcinomas compared with squamous cell carcinomas. Finally, high p-ACC was an independent marker for prediction of better survival in lung adenocarcinoma patients. Median overall survival was longer in patients with p-ACC-positive than those with p-ACC-negative tumors (96 versus 44 months, P = .04). In conclusion, our observations provide complete information about the pattern and levels of LKB1 and p-ACC immunostaining in normal tissues and in lung tumors, and highlight the special relevance of abnormalities of the LKB1 pathway in lung adenocarcinoma.

Prognostic value of KIT expression in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very aggressive disease, with poor survival rates despite standard treatment with combination chemotherapy with or without radiotherapy. Further insights into the molecular biology of this malignant tumour are needed to improve the therapeutic approaches and outcome. KIT protein is expressed in SCLC, and its kinase activity has been implicated in the pathophysiology of many tumours, including SCLC. The purpose of this study was to evaluate the prevalence of KIT expression in patients with SCLC and its prognostic value. METHODS: We performed an inmunohistochemical analysis of 204 SCLC samples to determine KIT protein expression. The relationship between KIT expression and clinicopathological parameters was evaluated. Univariate and multivariate analyses were performed to define its prognostic significance. RESULTS: KIT expression was observed in 149 of 204 tumour tissues (73%). KIT expression was associated with advanced disease and with decreased incidence of bone metastases. No significant differences were observed for time to disease progression (TTP) (9.1% versus 6.2% at 3 years, p=0.6) or overall survival (OS) (10.7% versus 6.9% at 3 years, p=0.37) among patients with KIT positive versus negative tumours, respectively. Multivariate analysis showed that sex, tumour stage, albumin levels and response to therapy were the only independent predictors for survival. CONCLUSION: KIT protein is expressed in a high percentage of SCLC tumours. In our study population, however, the expression of KIT had no significant impact on survival.

[Risk factors in bronchogenic carcinoma surgery]. / Parámetros de riesgo en la cirugía del carcinoma broncogénico.

OBJECTIVE: To analyze the factors that determine the risk of morbidity and mortality associated with lung resection in patients with bronchogenic carcinoma. PATIENTS AND METHODS: Prospective multicenter study conducted between October 1, 1993 and September 30, 1997 in the 19 hospitals that make up the Bronchogenic Carcinoma Cooperative Group. During the study period, 2994 patients with bronchogenic carcinoma underwent surgery. The morbidity and mortality data at 30 days from all centers were recorded in a single registry. RESULTS: Major resection was performed in 2491 patients, whereas 212 underwent minor resection. The resection had to be extended in 296 and exploratory thoracotomy was carried out in 291. Postoperative complications were reported in 1057 patients (35.2%). Complications directly related to surgery were the most common (22.9%), followed by respiratory (19.5%) and cardiovascular (10.7%) complications. Of the patients with complications, 654 patients (21.8%) had only 1, whereas 403 (13.4%) had more than 1. After classification of complications, 21% were found to be minor and 14.2% were major. Mortality at 30 days was 6.8% (204 patients), and strongly linked to the presentation of major complications--40.8% of those with such complications died. CONCLUSIONS: Surgical treatment of bronchogenic carcinoma in Spain is associated with high morbidity and mortality. The morbidity reported in the present study lies in the middle of the ranges found in the literature, whereas mortality lies at the high end of the range. The presence of major complications and/or multiple complications should be considered as strong risk factors.

Tratamiento multimodal en el carcinoma broncogénico no microcítico (N2) clínico: ¿cuál es la respuesta?. Respuesta del autor / On 'Multimodal treatment of clinical non-small cell N2 bronchogenic carcinoma: what is the answer?'. Author’s reply

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