RESUMO
Myometrial invasion (MI) as a percentage (%MI), categorized into <50 or ≥50 %, is an important predictor of prognosis in endometrial carcinoma. Recent studies suggest that tumor-free distance (TFD) to serosa and the absolute depth of invasion (DOI) might be stronger predictors of prognosis. Although reproducibility is important in clinical practice for patient prognostication and treatment, reproducibility of these methods for the measurement of MI is largely unknown. One or two slides from 50 patients with FIGO stage I endometrioid endometrial carcinoma were viewed by seven gynecological pathologists, who were requested to measure %MI, TFD, and DOI. We categorized %MI as <50 % (including no MI) or ≥50 %, TFD as ≤1.75 or >1.75 mm (including no MI), ≤7 or >7 mm (including no MI), and ≤10 or >10 mm (including no MI) and DOI as <4 mm (including no MI) or ≥4 mm. Light's kappa for multi-rater agreement was calculated. The %MI, TFD, and DOI could be measured in 88, 83, and 79 % of cases, respectively. Kappa was 0.75 for %MI, 0.77, 0.73, and 0.69 respectively for TFD with cutoffs of 1.75, 7, and 10 mm, and 0.59 for DOI. Pathologists reach substantial agreement when measuring %MI and TFD and moderate agreement when measuring DOI. The %MI can be measured in more cases than TFD and DOI. This supports the use of %MI in daily clinical practice, but future studies should compare %MI and TFD more extensively, including inter-observer variability.
Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Variações Dependentes do Observador , Prognóstico , Reprodutibilidade dos TestesRESUMO
PURPOSE: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Despite aggressive chemotherapy, more than 30% of patients do not respond and develop bone or lung metastasis. Oncolytic adenoviruses engineered to specifically destroy cancer cells are a feasible option for osteosarcoma treatment. VCN-01 is a replication-competent adenovirus specifically engineered to replicate in tumors with a defective RB pathway, presents an enhanced infectivity through a modified fiber and an improved distribution through the expression of a soluble hyaluronidase. The aim of this study is to elucidate whether the use of VCN-01 would be an effective therapeutic strategy for pediatric osteosarcoma. EXPERIMENTAL DESIGN: We used osteosarcoma cell lines established from patients with metastatic disease (531MII, 678R, 588M, and 595M) and a commercial cell line (143B). MTT assays were carried out to evaluate the cytotoxicity of VCN-01. Hexon assays were used to evaluate the replication of the virus. Western blot analysis was performed to assess the expression levels of viral proteins and autophagic markers. The antitumor effect of VCN-01 was evaluated in orthotopic and metastatic osteosarcoma murine animal models. RESULTS: This study found that VCN-01, a new generation genetically modified oncolytic adenovirus, administered locally or systemically, had a potent antisarcoma effect in vitro and in vivo in mouse models of intratibial and lung metastatic osteosarcoma. Moreover, VCN-01 administration showed a safe toxicity profile. CONCLUSIONS: These results uncover VCN-01 as a promising strategy for osteosarcoma, setting the bases to propel a phase I/II trial for kids with this disease. Clin Cancer Res; 22(9); 2217-25. ©2015 AACR.
Assuntos
Adenoviridae/genética , Neoplasias Ósseas/virologia , Vírus Oncolíticos/genética , Osteossarcoma/virologia , Animais , Neoplasias Ósseas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Terapia Genética/métodos , Células HEK293 , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/virologia , Camundongos , Camundongos Nus , Terapia Viral Oncolítica/métodos , Pediatria , Replicação Viral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Osteosarcoma is the most common malignant bone tumor in children and adolescents. The presence of metastases and the lack of response to conventional treatment are the major adverse prognostic factors. Therefore, there is an urgent need for new treatment strategies that overcome both of these problems. Our purpose was to elucidate whether the use of the oncolytic adenovirus Δ24-RGD alone or in combination with standard chemotherapy would be effective, in vitro and in vivo, against osteosarcoma. Our results showed that Δ24-RGD exerted a potent antitumor effect against osteosarcoma cell lines that was increased by the addition of cisplatin. Δ24-RGD osteosarcoma treatment resulted in autophagy in vitro that was further enhanced when combined with cisplatin. Of importance, administration of Δ24-RGD and/or cisplatin, in novel orthotopic and two lung metastatic models in vivo resulted in a significant reduction of tumor burden meanwhile maintaining a safe toxicity profile. Together, our data underscore the potential of Δ24-RGD to become a realistic therapeutic option for primary and metastatic pediatric osteosarcoma. Moreover, this study warrants a future clinical trial to evaluate the safety and efficacy of Δ24-RGD for this devastating disease.
Assuntos
Adenoviridae/fisiologia , Cisplatino/uso terapêutico , Oligopeptídeos/uso terapêutico , Vírus Oncolíticos/fisiologia , Osteossarcoma/terapia , Adolescente , Animais , Autofagia/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Criança , Cisplatino/farmacologia , Terapia Combinada , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Camundongos Nus , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/ultraestrutura , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: The cortactin (CTTN) gene has been found, by transcriptomic profiling, to be overexpressed in pediatric osteosarcoma. The location of CTTN at 11q13 and the role of cortactin in cytoskeleton restructuring make CTTN of interest as a potential biomarker for osteosarcoma. MATERIALS AND METHODS: Osteoblasts were isolated from 20 high-grade osteosarcomas before chemotherapy, and paired with cell samples from normal tissue, prior to RNA expression analysis on HG-U133A chips (Affymetrix). Semiquantitative CTTN mRNA expression was analyzed by real-time PCR. An osteosarcoma tissue microarray (TMA) containing 233 tissue spots from 48 patients was used for an immunohistochemical (IHC) study of cortactin. RESULTS: Transcriptomic profiling and real-time PCR analysis indicated increased CTTN expression in osteosarcomas (p = 0.001, Student's T test). TMA IHC showed cortactin to be present more frequently and in greater abundance in osteosarcomas than non-tumoral osteoblastic samples (p< 0.006, Mann-Withney test). Analysis of clinical outcomes indicated that overall survival for patients with primary tumors positive for cortactin was significantly lower than that for patients with cortactin negative (or only weakly staining) tumors (p = 0.0278, Log-rank test). CONCLUSIONS: Our preliminary data support the hypothesis that over-expression of cortactin, contained in the 11q13 amplicon, is involved in osteosarcoma carcinogenesis. The potential of cortactin overexpression as a biomarker for osteosarcoma is consolidated.
Assuntos
Neoplasias Ósseas/genética , Cortactina/genética , Expressão Gênica , Osteossarcoma/genética , Regulação para Cima , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Cortactina/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , Análise Serial de Tecidos , Células Tumorais Cultivadas , Adulto JovemRESUMO
Epithelial ovarian carcinoma is still the most common cause of death from gynaecological cancer in USA and western Europe. The optimal therapy of epithelial ovarian carcinoma requires participation of a multidisciplinary team - from diagnosis through the entire natural history of each individual patient. Only 20-30% of patients are diagnosed at the initial stage, when appropriate staging surgery in combination with adjuvant chemotherapy for high-risk patients can be curative. Treating patients with advanced disease consists of a staging surgery with maximum cytoreductive effort, followed by chemotherapy with a combination of taxane and carboplatin. Unfortunately, the majority of patients with advanced disease will relapse and become candidates for therapy that comprises individualised chemotherapy, and surgery in selected cases. For this reason, there is still a need for new treatments and strategies in the first-line setting.
Assuntos
Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Animais , Carcinoma/diagnóstico , Carcinoma/metabolismo , Carcinoma/terapia , Prática Clínica Baseada em Evidências/tendências , Feminino , Humanos , Imuno-Histoquímica , Terapia Neoadjuvante , Estadiamento de Neoplasias/métodos , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologiaRESUMO
Surgery for rectal cancer continues to develop towards improving local control and overall survival, maintaining quality of life and preserving sphincter, genitourinary and sexual function. The multidisciplinary approach integrated in a team of different specialists ensures an individualised treatment for each patient with rectal cancer. Thus, the role of the pathologist has acquired an important relevance, not only in diagnosis, management and evaluation of the surgical specimen, but also for selection of the best adjuvant treatment. Parameters such as macroscopic quality of the mesorectum, status of the circumferential margin and lymph node harvest are considered basic criteria by current guidelines. Additionally, consistency in reporting based on the histologic classification proposed by the World Health Organization (WHO) is mandatory, along with inclusion into the pathologic report of current criteria for tumour node metastasis (TNM) staging, assessment of response to neoadjuvant chemoradiation therapy and clinically relevant molecular studies. Detection of defects in mismatch repair genes and mutational analysis of specific genes should be included as predictive markers for therapy.
Assuntos
Carcinoma , Procedimentos Cirúrgicos do Sistema Digestório/normas , Estadiamento de Neoplasias/normas , Neoplasias Retais , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/tendências , Humanos , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/tendências , Controle de Qualidade , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Padrões de ReferênciaRESUMO
PURPOSE: Osteosarcoma is the most prevalent bone tumor in children and adolescents. At present, the mechanisms of initiation, maintenance, and metastasis are poorly understood. The purpose of this study was to identify relevant molecular targets in the pathogenesis of osteosarcoma. EXPERIMENTAL DESIGN: Tumor chemonaive osteoblastic populations and paired control normal osteoblasts were isolated and characterized phenotypically from seven osteosarcoma patients. Global transcriptomic profiling was analyzed by robust microarray analysis. Candidate genes were confirmed by real-time PCR and organized in molecular pathways. EBF2 and osteoprotegerin (OPG) levels were determined by real-time PCR and OPG protein levels were assessed by ELISA. Immunohistochemical analysis was done in a panel of 46 osteosarcoma samples. Silencing of EBF2 was achieved by lentiviral transduction of short hairpin RNA. Apoptosis was determined by caspase-3/7 activity. RESULTS: A robust clustered transcriptomic signature was obtained in osteosarcoma. Transcription factor EBF2, a known functional bone regulator, was among the most significantly overexpressed genes. Immunohistochemical analysis showed that osteosarcoma is expressed in approximately 70% of tumors analyzed. Because EBF2 was shown previously to act as a transcriptional activator of OPG, elevated levels of EBF2 were associated with high OPG protein levels in osteosarcoma samples compared with normal osteoblastic cells. Knockdown of EBF2 led to stunted abrogation of OPG levels and increased sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. CONCLUSIONS: These findings suggest that EBF2 represents a novel marker of osteosarcoma. EBF2 up-regulation may be one of the mechanisms involved in the high levels of OPG in osteosarcoma, contributing to decrease TRAIL-induced apoptosis and leading to TRAIL resistance.
Assuntos
Apoptose/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Neoplasias Ósseas/genética , Osteoprotegerina/fisiologia , Osteossarcoma/genética , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Adolescente , Adulto , Apoptose/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Células Cultivadas , Criança , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Análise por Pareamento , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Análise de Sobrevida , Adulto JovemRESUMO
With a view to identify the proteins involved in transformation, metastasis or chemoresistance in pediatric osteosarcoma, we carried out a new experimental approach based on comparison of the proteomic profile of paired samples of osteosarcoma and normal bone tissues from the same patient. The proteomic profiles of five pairs of cell lines (normal vs tumoral) were obtained by two-dimensional difference gel electrophoresis. We detected 56 differential protein spots (t test, p < 0.05). Subsequent protein characterization by nano-LC-ESI-MS/MS enabled us to identify some of these proteins, 16 of which were chosen on the basis of the change of their relative abundance between osteosarcomas and paired normal bones and also because their involvement was supported by the genomic analysis. Two of the 16 proteins, Alpha-crystallin B chain (CRYAB) and ezrin (EZR1), were selected for further studies: an immunohistochemical analysis of a TMA (tissue microarray) and real-time PCR for a set of 14 osteosarcoma/normal-bone pairs. The results of this second tier of studies confirmed that there were significant increases in the amounts of CRYAB and ezrin, especially in advanced stages of the disease. Our overall conclusion is that proteomic profiling of paired samples of osteosarcoma and normal bone tissues from the same patient is a practicable and potentially powerful way of initiating and proceeding with a search for proteins and genes involved in pediatric osteosarcoma.
Assuntos
Neoplasias Ósseas/metabolismo , Osso e Ossos/metabolismo , Proteínas de Neoplasias/análise , Osteossarcoma/metabolismo , Proteômica/métodos , Adolescente , Neoplasias Ósseas/química , Osso e Ossos/química , Criança , Cromatografia Líquida , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Eletroforese em Gel Bidimensional , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Osteossarcoma/química , Reação em Cadeia da Polimerase , Estatísticas não Paramétricas , Espectrometria de Massas em Tandem , Análise Serial de Tecidos , Células Tumorais Cultivadas , Adulto Jovem , Cadeia B de alfa-Cristalina/genética , Cadeia B de alfa-Cristalina/metabolismoRESUMO
Smooth muscle tumors (SMTs) are the most frequent mesenchymal tumors of the uterus. The majority of the uterine SMTs are readily classificable as benign or malignant based on their gross and microscopic appearances. However, when unusual features are seen in some leiomyoma variants, the differential diagnosis with a leiomyosarcoma may become challenging. Moreover, diagnostic criteria for the different subtypes of leiomyosarcoma are not uniform. Finally, non-smooth muscle tumors that originate in the uterus may show overlapping histologic and even immunohistochemical features with uterine SMTs, more commonly with the spindle and epithelioid variants, complicating their correct classification. The diagnosis of malignant uterine SMTs has important prognostic and therapeutic implications. This review provides a practical approach to the diagnosis of uterine leiomyosarcoma based on a systematic assessment of histologic parameters as well as a systematic approach to its differential diagnosis based on histologic and immunohistochemical features.
Assuntos
Patologia/educação , Tumor de Músculo Liso/diagnóstico , Neoplasias Uterinas/diagnóstico , Feminino , Humanos , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/patologia , Índice Mitótico , Necrose , Tumor de Músculo Liso/patologia , Neoplasias Uterinas/patologiaRESUMO
Vascular endothelial growth factor (VEGF) serum levels and VEGF and cellular expression were prospectively analyzed in 60 patients (group A consisted of asymptomatic patients or patients presenting mild dysmenorrhea; 30 women comprised group B severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia) who underwent surgery for cystic ovarian endometriosis to asses whether a correlation exists among VEGF serum levels, VEGF cellular expression, and pelvic pain. No differences were found in VEGF serum levels and VEGF cellular expression between both groups. Therefore, we conclude that pain symptoms in ovarian endometriosis are not correlated with VEGF serum levels and VEGF cellular expression.
Assuntos
Endometriose/sangue , Endometriose/complicações , Doenças Ovarianas/sangue , Doenças Ovarianas/complicações , Dor Pélvica/etiologia , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Endometriose/metabolismo , Feminino , Humanos , Cistos Ovarianos/metabolismo , Doenças Ovarianas/metabolismo , Dor Pélvica/sangue , Dor Pélvica/metabolismo , Estudos Prospectivos , Distribuição TecidualRESUMO
PURPOSE: An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. A key regulatory mechanism of the MAPKs [extracellular signal-regulated kinase (ERK); c-jun NH(2)-terminal kinase (JNK); and p38] is the dual specificity phosphatase CL100, also called MAPK phosphatase-1 (MKP-1). This study was designed to examine the involvement of CL100/MKP-1 and stress-related MAPKs in lung cancer. EXPERIMENTAL DESIGN: We assessed the expression of CL100/MKP-1 and the activation of the MAPKs in a panel of 18 human cell lines [1 primary normal bronchial epithelium, 8 non-small cell lung cancer (NSCLC), 7 small cell lung cancer (SCLC), and 2 carcinoids] and in 108 NSCLC surgical specimens. RESULTS: In the cell lines, CL100/MKP-1 expression was substantially higher in NSCLC than in SCLC. P-ERK, P-JNK, and P-p38 were activated in SCLC and NSCLC, but the degree of their activation was variable. Immunohistochemistry in NSCLC resection specimens showed high levels of CL100/MKP-1 and activation of the three MAPK compared with normal lung. In univariate analysis, no relationship was found among CL100/MKP-1 expression and P-ERK, P-JNK, or P-p38. Interestingly, high CL100/MKP-1 expression levels independently predicted improved survival in multivariate analysis. JNK activation associated with T(1-2) and early stage, whereas ERK activation correlated with late stages and higher T and N. Neither JNK nor ERK activation were independent prognostic factors when studied for patient survival. CONCLUSIONS: Our data indicate the relevance of MAPKs and CL100/MKP-1 in lung cancer and point at CL100/MKP-1 as a potential positive prognostic factor in NSCLC. Finally, our study supports the search of new molecular targets for lung cancer therapy within the MAPK signaling pathway.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/enzimologia , Proteínas de Ciclo Celular/biossíntese , Proteínas Imediatamente Precoces/biossíntese , Neoplasias Pulmonares/enzimologia , Fosfoproteínas Fosfatases/biossíntese , Proteínas Tirosina Fosfatases/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Northern Blotting , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/terapia , Linhagem Celular Tumoral , DNA Complementar/metabolismo , Fosfatase 1 de Especificidade Dupla , Feminino , Humanos , Imuno-Histoquímica , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Pulmonares/terapia , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Proteína Fosfatase 1 , RNA/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Tempo , Resultado do Tratamento , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The fragile histidine triad (FHIT) gene, located at chromosome 3p14.2, is deleted in many solid tumors, including lung cancer. Its protein product is presumed to have tumor suppressor function. We investigated the incidence of loss of heterozygosity and loss of FHIT expression in a series of non-small-cell lung carcinomas and its correlation to apoptosis, proliferation index and prognosis. FHIT expression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissues from 54 squamous cell carcinomas (SCC) and 44 adenocarcinomas (AC) of the lung. DNA from frozen tumor and corresponding normal tissues were analyzed for allelic losses at two loci located internal (D3S1300, D3S1234) and three loci in flanking regions centromeric and telomeric (D3S1210, D3S1312, D3S1313) to the FHIT gene. Apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL). Proliferation index was determined with ki-67 and flow cytometric analysis. We correlated the results with tumor histology, prognosis and some immunohistochemical markers (p53, bcl-2, bax, c-myc, p21(waf1), cyclin-D1). FHIT expression was related to tumor histology: 52 of 54 (96.3%) SCC and 20 of 44 (45.5%) AC were negative for FHIT (P<0.0001). We found LOH at 3p14.2 in 67.8% of the 98 cases: 72.3% of SCC and 61.4% of AC. Loss of FHIT expression was associated with a higher proliferation index (ki-67, P=0.007; flow cytometry, P<0.004) and lower apoptotic index (P=0.018). LOH at FHIT gene were associated to a high proliferation (flow cytometry, P<0.001) and lower apoptotic level (P=0.043). The log-rank test demonstrated a significant inverse correlation (P=0.039) between loss of FHIT expression and patient survival. FHIT plays an important role in the development of non-small-cell lung cancer, particularly in SCC. Loss of FHIT protein is correlated with a high proliferation and low apoptotic index in tumor cells, and is an independent prognostic indicator for the clinical outcome in patients with these tumors.
Assuntos
Hidrolases Anidrido Ácido/metabolismo , Apoptose , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Divisão Celular , DNA de Neoplasias/análise , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Humanos , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Perda de Heterozigosidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da PolimeraseRESUMO
hnRNP A2/B1 has been suggested as a useful early detection marker for lung carcinoma. hnRNP A2/B1 is a member of a large family of heterogeneous nuclear ribonucleoproteins (hnRNP proteins) involved in a variety of functions, including regulation of transcription, mRNA metabolism, and translation. In lung cancer, we have evaluated the expression and cellular localization of several members of the hnRNP family, hnRNP A1, A2, B1, C1, C2 and K. 16 cell lines (SCLC and NSCLC) and biopsies from 32 lung cancer patients were analyzed. Our results suggest that, besides hnRNP A2/B1, the expression of other members of the hnRNP family is altered both in SCLC and NSCLC. In the biopsies, negative or low expression of the hnRNP proteins analyzed was observed in normal epithelial cells whereas lung cancer cells showed highly intense nuclear or cytoplasmic immunolocalization. In all the lung cancer cell lines, the mRNA for all the hnRNP proteins was detected. In general, higher levels of hnRNP mRNAs were found in SCLC as compared with NSCLC. Our results also suggest that the expression and processing of each hnRNP protein in lung cancer is independently regulated and is not exclusively related to proliferation status. In SCLC cell lines, hnRNP A1 protein expression correlated with that of Bcl-x(L). In the lung cancer cell lines, hnRNP K protein localization varied with the cellular confluence.