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In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.
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Neoplasias de la Mama , Desastres , Accidente Nuclear de Fukushima , Consulta Remota , Telepatología , Humanos , Femenino , Biopsia del Ganglio Linfático Centinela , Secciones por Congelación , JapónRESUMEN
Background: Anatomical pathology care services play an essential role in cancer diagnosis through histological analysis, effective treatment of patients, and determination of prognosis. Therefore, quality control is necessary for the diagnosis of pathology. Based on this need, telepathology technology is rapidly developing in the world. This study aimed to share the experience of implementing telepathology case consultation between Mongolian and Japanese expert pathologists. Methods: The study included 173 cases that required telepathology consultation, which was complicated and doubtful in diagnosis, submitted by Mongolian pathologists between May 2019 and April 2022. The scanned digital slides were transmitted with the help of the LOOKREC cloud-based system, and the expert pathologists of Hiroshima University Hospital, Japan, browsed the images through the data on the internet and their advice and made a mutual diagnosis. Results: During the study period, 173 cases were consulted. Out of 58.4% of all cases, consultation reports were released in 2022. The majority of the cases in 2020 had a mean standard deviation turn-around time of 4.2±6.2 days. The most cases were from the lung and mediastinum were 29.4%, followed by head and neck at 12.6%, the bone at 11.9%, lymph nodes at 8.4%, GIT at 7.7%, soft tissues at 6.3%, etc. Comparing the sample submission of biopsy and cytology was significantly higher in the under 10 years of an experienced group than over 10 years of an experienced group (p<.005). The diagnostic agreement between submitter Mongolian pathologists and expert Japanese pathologists was 82.7%, and disagreement was 17.3% of all cases, with a sensitivity of 67.3% and specificity of 85.5%. Conclusions: Telepathology could save many lost opportunities and play an essential role in developing quality control and surgical pathology in Mongolia. This digital technology and the appropriate strategy and policy of the government could accelerate the overall pathology field development.
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Although the routine use of immunohistochemistry has improved the accuracy of histopathologic diagnosis in clinical practice, new methods for discovering novel diagnostic markers are still needed. We sought new diagnostic markers for malignant pleural mesothelioma (MPM) using a reverse translational approach with limited archival tissues from a very rare case. Total RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues of a synchronous collision tumor consisting of MPM and pulmonary adenocarcinoma (PAC) was employed for gene expression profiling (GEP) analysis. Among the 54 genes selected by GEP analysis, we finally identified the following two candidate MPM marker genes: PHGDH and TRIM29. Immunohistochemical analysis of 48 MM and 20 PAC cases showed that both PHGDH and TRIM29 had sensitivity and specificity almost equivalent to those of calretinin (sensitivity 50% and 46% vs. 63%, and specificity 95% and 100% vs. 100%, respectively). Importantly, of the 23 epithelioid MMs, all 3 calretinin-negative cases were positive for TRIM29. These two markers may be diagnostically useful for immunohistochemical distinction between MPMs and PACs. This successful reverse translational approach based on FFPE samples from one very rare case encourages the further use of such samples for the development of novel diagnostic markers.
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Histological distinction between epithelioid mesothelioma (EM) and reactive mesothelial hyperplasia (RMH) can be challenging. The aim of this study was to assess the diagnostic utility of Survivin, Ki-67, and loss of BRCA1-associated protein 1 (BAP1) expressions in distinguishing EM from RMH using immunohistochemistry. Formalin-fixed, paraffin-embedded specimens from 78 cases of EM and 80 cases of RMH were immunohistochemically examined for Survivin, BAP1, and Ki-67. In addition, receiver operating characteristic curve analyses were performed to establish the cut-off values for Survivin and Ki-67 labelling indices. Survivin (cut-off value: 5%) had 67.7% sensitivity and 100% specificity, while Ki-67 (cut-off value: 10%) had 85.1% sensitivity and 87.5% specificity, and BAP1 had 66.2% sensitivity and 100% specificity for the differentiation of EM from RMH. Among the combinations of two markers, the combination of Survivin and BAP1 (Survivin-positive and/or BAP1-loss finding) had the highest diagnostic accuracy (sensitivity: 89.8%; specificity: 100%; accuracy: 95.3%). We recommend using the combination of Survivin and BAP1 to distinguish EM from RMH.
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As there are currently no absolute immunohistochemical positive markers for the definite diagnosis of malignant epithelioid mesothelioma, the identification of additional "positive" markers that may facilitate this diagnosis becomes of clinical importance. Therefore, the aim of this study was to identify novel positive markers of malignant mesothelioma. Whole genome gene expression analysis was performed using RNA extracted from formalin-fixed paraffin-embedded tissue sections of epithelioid mesothelioma and pulmonary adenocarcinoma. Gene expression analysis revealed that disabled homolog 2 (DAB2) and Intelectin-1 had significantly higher expression in epithelioid mesothelioma compared with that in pulmonary adenocarcinoma. The increased mRNA expression of DAB2 and Intelectin-1 was validated by reverse transcriptase polymerase chain reaction of RNA from tumor tissue and protein expression was validated by Western blotting of 5 mesothelioma cell lines. The utility of DAB2 and Intelectin-1 in the differential diagnosis of epithelioid mesothelioma and pulmonary adenocarcinoma was examined by an immunohistochemical study of 75 cases of epithelioid mesothelioma and 67 cases of pulmonary adenocarcinoma. The positive rates of DAB2 and Intelectin-1 expression in epithelioid mesothelioma were 80.0% and 76.0%, respectively, and 3.0% and 0%, respectively, in pulmonary adenocarcinoma. Immunohistochemically, the sensitivity and specificity of DAB2 was 80% and 97% and those of Intelectin-1 were 76% and 100% for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma. In conclusion, DAB2 and Intelectin-1 are newly identified positive markers of mesothelioma and have potential to be included in future immunohistochemical marker panels for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma.
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Proteínas Adaptadoras Transductoras de Señales/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Citocinas/genética , Perfilación de la Expresión Génica , Lectinas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mesotelioma/genética , Mesotelioma/patología , Análisis por Micromatrices , Proteínas Supresoras de Tumor/genética , Adenocarcinoma/química , Adenocarcinoma del Pulmón , Proteínas Reguladoras de la Apoptosis , Biomarcadores de Tumor/análisis , Diferenciación Celular , Proteínas Ligadas a GPI/genética , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/química , Mesotelioma/química , Mesotelioma MalignoRESUMEN
Sarcomatoid mesothelioma, a histological subtype of malignant pleural mesothelioma, is a very aggressive tumor with a poor prognosis. Histological diagnosis of sarcomatoid mesothelioma largely depends on the histomorphological feature of spindled tumor cells with immunohistochemical reactivity to cytokeratins. Diagnosis also requires clinico-radiological and/or macroscopic evidence of an extrapulmonary location to differentiate it from lung sarcomatoid carcinoma. Although there are promising immunohistochemical antibody panels to differentiate mesothelioma from lung carcinoma, a consensus on the immunohistochemical markers that distinguish sarcomatoid mesothelioma from lung sarcomatoid carcinoma has not been reached and requires further study. We performed whole gene expression analysis of formalin-fixed paraffin-embedded tissue from sarcomatoid mesothelioma and lung sarcomatoid carcinoma and observed significant differences in the expression of MUC4 and other genes between sarcomatoid mesothelioma and lung sarcomatoid carcinoma. Immunohistochemistry demonstrated that MUC4 was expressed in the spindled tumor cells of lung sarcomatoid carcinoma (21/29, 72%) but was not expressed in any sarcomatoid mesothelioma (0/31, 0%). To differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma, negative MUC4 expression showed 100% sensitivity and 72% specificity and accuracy rate of 87%, which is higher than immunohistochemical markers such as calretinin, D2-40 and Claudin-4. Therefore, we recommend to include MUC4 as a novel and useful negative immunohistochemical marker for differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma.
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Carcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Mucina 4/biosíntesis , Neoplasias Pleurales/diagnóstico , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Perfilación de la Expresión Génica/métodos , Humanos , Inmunohistoquímica , Mesotelioma Maligno , Mucina 4/análisis , Sensibilidad y EspecificidadRESUMEN
AIMS: The aims of this study were to clarify the usefulness of immunohistochemistry in the differential diagnosis of epithelioid mesothelioma with a solid growth pattern [solid epithelioid mesothelioma (SEM)] and poorly differentiated squamous cell carcinoma (PDSCC), and to confirm the validity of a specific type of antibody panel. Additionally, we aimed to clarify the pitfalls of immunohistochemical analyses. METHODS AND RESULTS: Formalin-fixed paraffin-embedded specimens from 36 cases of SEM and 38 cases of PDSCC were immunohistochemically examined for calretinin, podoplanin (D2-40), Wilms' tumour gene product (WT1), cytokeratin (CK) 5/6, p40, p63, carcinoembryonic antigen (CEA), epithelial-related antigen (MOC31), claudin-4, thyroid transcription factor-1 (TTF-1), and napsin A. WT1 showed the highest diagnostic accuracy (85.1%) as a mesothelial marker, and CEA, p40 and claudin-4 showed higher diagnostic accuracies (95.9%, 94.6%, and 93.2%, respectively) as carcinoma markers. Calretinin (diagnostic accuracy: 75.7%), D2-40 (diagnostic accuracy: 67.6%), CK5/6 (diagnostic accuracy: 63.5%), TTF-1 (diagnostic accuracy: 55.4%) and napsin A (diagnostic accuracy: 52.7%) could not differentiate between SEM and PDSCC. Among these markers, the combination of calretinin and WT1 showed the highest diagnostic accuracy (86.5%) as a positive marker, and the combination of p40 and CEA showed the highest diagnostic accuracy (97.3%) as a negative marker. The combination of CEA and claudin-4 also showed relatively high diagnostic accuracy (94.6%) as a negative marker. CONCLUSIONS: We recommend the combination of WT1 and calretinin as a positive maker, and the combination of CEA and claudin-4 as a negative marker, for differential diagnoses of SEM and PDSCC.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Mesotelioma Maligno , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To elucidate differences in the level and localization of pleural irregularities in early malignant pleural mesothelioma (eMPM) and benign asbestos pleural effusion (BAPE) using CT. STUDY DESIGN: Retrospective assessment of CT findings of consecutive patients with BAPE at a single centre and patients with eMPM reported in Japanese vital statistics. METHODOLOGY: Thirty-six patients with confirmed diagnoses of BAPE and sixty-six patients with confirmed diagnoses of eMPM (mesothelioma stages T1 or T2) were included. Informed consent, CT scans, and clinical and pathologic details were obtained for all patients and were reviewed by one radiologist, two pathologists, and two pulmonologists. Asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening were assessed in all patients. RESULTS: Prevalence of asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening was significantly higher in the BAPE group. Low-level irregularity was more common in the BAPE group (p<0.001), whereas high-level irregularity, mediastinal localization, and interlobar fissure were more prevalent in the eMPM group (p<0.001). Interlobar pleural irregularity was not observed in any patients in the BAPE group, although 55% of patients in the eMPM group showed interlobar pleural irregularity. Mediastinal pleural involvement was observed in 74% of patients in the eMPM group and had a positive predictive value of 89%. CONCLUSION: This study demonstrates that the level and localization of plural irregularities significantly differed between patients with BAPE and eMPM. Large-scale prospective studies are needed to fully establish the diagnostic utility of such differences.
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Asbestosis/patología , Neoplasias Pulmonares/patología , Mediastino/patología , Mesotelioma/patología , Pleura/patología , Derrame Pleural/patología , Tomografía Computarizada por Rayos X , Anciano , Asbestosis/diagnóstico por imagen , Femenino , Humanos , Japón , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Mesotelioma/diagnóstico por imagen , Mesotelioma Maligno , Persona de Mediana Edad , Pleura/diagnóstico por imagen , Derrame Pleural/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
AIM: The objective of this study was to determine the computed tomographic (CT) features of malignant peritoneal mesothelioma (MPM). PATIENTS AND METHODS: We analyzed CT features of MPM cases and compared them to those of other malignant conditions (non-MPM). RESULTS: Multiple nodular lesions occurred more frequently in the MPM group compared to non-MPM cases (p=0.013). Thickening of the mesentery was detected more frequently in MPM cases than in non-MPM cases (56% vs. 18%, p=0.029). Pleural plaques were detected in 13 cases (45%) in the MPM group but were not detected in the non-MPM group. The MPM-CT index score, determined in each case as the sum of the findings which are potentially characteristic of MPM, was significantly higher in MPM than in non-MPM cases (p=0.001). CONCLUSION: MPM presented characteristic CT findings, and the MPM-CT index may be useful for differential diagnosis of MPM.
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Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Mesotelioma/diagnóstico por imagen , Mesotelioma/patología , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Mesotelioma Maligno , Neoplasias Pleurales/patología , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: The purpose of this study was to clarify the characteristic findings of mesothelioma at the time of diagnosis, and determine precautions and guidelines for diagnosing mesothelioma early in imaging studies. MATERIALS AND METHODS: Overall, 327 patients with pleural mesothelioma were selected from 6030 patients who died of mesothelioma between 2003 and 2008 in Japan. Their imaging findings were examined retrospectively. RESULTS: Plaques were found in 35 % of computed tomography (CT) scans. Asbestosis, diffuse pleural thickening, and rounded atelectasis were found in only seven (2 %), five (2 %), and two cases (1 %), respectively. Pleural thickening findings on CT scans were classified into four stages: no irregularity, mild irregularity, high irregularity, and mass formation. Overall, 18 % of cases did not show a clear irregularity. Localized thickening was observed in the mediastinal (77 %) and basal (76 %) pleura and in the interlobar fissure (49 %). Eight percent of cases did not have any thickening in these three areas. CONCLUSIONS: Upon examination of the CT scans at diagnosis, 18 % of mesothelioma cases did not show a clear irregularity. When diagnosing pleural effusion of unknown etiology, it is necessary to consider the possibility of mesothelioma even when no plaque and pleural irregularity are observed.
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Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Mesotelioma/diagnóstico por imagen , Mesotelioma/mortalidad , Neoplasias Pleurales/diagnóstico por imagen , Neoplasias Pleurales/mortalidad , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón , Masculino , Mesotelioma Maligno , Persona de Mediana Edad , Pleura/diagnóstico por imagen , Estudios Retrospectivos , Adulto JovenRESUMEN
CD9 is involved in cell growth, adhesion and motility and its expression is reported to be of prognostic significance in various types of human malignancies. We found increased cell migration in the mesothelioma cell lines MSTO-211H and TUM1 following in vitro shRNA-mediated knockdown of CD9 expression. We investigated CD9 expression in 112 malignant pleural mesotheliomas. CD9 expression was observed in 62 of 71 epithelioid, 13 of 20 biphasic and only 1 of 21 sarcomatoid mesotheliomas. Among the epithelioid mesotheliomas (EMs), CD9 expression was observed in all of the 33 cases with a differentiated type (EM-D) and in 29 of the 38 cases with a less-differentiated type (EM-LD). Patients with CD9 expression showed higher 1- and 2-year survival rates (63 and 25%) compared to the patients without CD9 expression (39 and 11%). Univariate analysis revealed that patients with CD9 expression demonstrated a more favorable survival (P=0.0025) along with other clinicopathological factors, including age younger than 60 years, IMIG stage I-II, epithelioid histology, EM-D and patients who underwent extrapleural pneumonectomy or received chemotherapy. Multivariate analysis identified CD9 expression as an independent prognostic factor with a hazard ratio (HR) of 1.99 in the analysis of all mesotheliomas (P=0.0261) and an HR of 2.60 in the analysis of EMs (P=0.0376). CD9 expression is an independent favorable prognostic marker of malignant mesothelioma.
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Biomarcadores de Tumor/metabolismo , Movimiento Celular , Mesotelioma/mortalidad , Neoplasias Pleurales/mortalidad , Tetraspanina 29/metabolismo , Adhesión Celular , Diferenciación Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Masculino , Mesotelioma/metabolismo , Mesotelioma/terapia , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/terapia , Pronóstico , ARN Interferente Pequeño/genética , Tasa de Supervivencia , Tetraspanina 29/antagonistas & inhibidores , Tetraspanina 29/genética , Células Tumorales CultivadasRESUMEN
BACKGROUND: There are few reports concerning treatment strategies and their contributions to survival of patients with malignant mesothelioma (MM) in Japan. MATERIAL AND METHODS: We extracted all death cases due to MM between 2003 and 2008. The diagnosis of MM was confirmed in 929 cases. Histological subtypes was determined in 709 cases, including 396 (55.9%) epithelioid, 154 (21.7%) sarcomatoid, 126 (17.8%) biphasic, and 33 (4.7%) other types. RESULTS AND CONCLUSION: Median overall survival (OS) of all MM cases was 7.7 months (95% confidence interval, 7.1-8.3). Median OS of patients with epithelioid MM was significantly longer than that of patients with biphasic (p = 0.030) or sarcomatoid (p < 0.001) MM. Surgical resection was performed in 172 patients (18.5%) and 449 (48.3%) received systemic chemotherapy. Survival of patients treated with both surgery and systemic chemotherapy was favorable. Median OS of patients in the late phase of the study period (2006-2008) was significantly longer than that in the early phase (2003-2005) (8.1 vs. 7.5 months, p = 0.008). Independent favorable prognostic factors included age younger than 70 years, female gender, epithelioid subtype, and clinical stage I-III. Multivariate analysis demonstrated that patients who had radical surgery and systemic chemotherapy showed a longer survival, though this could be due to selection bias of patients.
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Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Mesotelioma/mortalidad , Mesotelioma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Terapia Combinada , Femenino , Humanos , Japón/epidemiología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Masculino , Mesotelioma/diagnóstico , Mesotelioma/epidemiología , Mesotelioma Maligno , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells, without established indicators to predict responsiveness to chemotherapy. EXPERIMENTAL DESIGN: Our study involving 79 MPM patients showed that 73.4% of MPM expressed CD26 on cell membrane. RESULTS: The majority of epithelioid and biphasic types of MPM expressed CD26 on the cell membrane, whereas the sarcomatoid type showed a lack of CD26 surface expression. Although the sarcomatoid type was associated with poor prognosis (P < 0.0001), no significant relationship between CD26 expression and survival was observed. On the contrary, there was a trend for an association between response rate to chemotherapy and CD26 expression (P = 0.053), with a higher level of CD26 expression more likely to be linked to better response to chemotherapy. Moreover, CD26 expression was a significant factor associated with improved survival in patients who received chemotherapy [median survival time (MST), 18.6 vs. 10.7 months, P = 0.0083]. Furthermore, CD26 expression was significantly associated with better prognosis in patients receiving non-pemetrexed-containing regimens (MST, 14.2 vs. 7.4 months, P = 0.0042), whereas there was no significant association between CD26 expression and survival time for patients receiving pemetrexed-containing regimens. Our in vitro and microarray studies showed that mesothelioma cells expressing high CD26 displayed high proliferative activity, and CD26 expression was closely linked to cell-cycle regulation, apoptosis, and chemotherapy resistance. CONCLUSIONS: Our results strongly suggest that CD26 is a clinically significant biomarker for predicting response to chemotherapy for MPM.
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Dipeptidil Peptidasa 4/genética , Mesotelioma/genética , Mesotelioma/mortalidad , Neoplasias Pleurales/genética , Neoplasias Pleurales/mortalidad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Dipeptidil Peptidasa 4/metabolismo , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Masculino , Mesotelioma/tratamiento farmacológico , Persona de Mediana Edad , Neoplasias Pleurales/tratamiento farmacológico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
By immunizing mice with a lung adenocarcinoma cell line, we previously established a murine IgG1 monoclonal antibody that recognizes a sialylated sugar chain designated Krebs von den Lungen-6 (KL-6). KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. The aim of this study was to determine whether KL-6 expression in tumors correlates with circulating KL-6 levels and whether circulating KL-6 has any prognostic value in patients with surgically resected non-small cell lung cancer (NSCLC). Immunohistochemical analysis of KL-6 expression was performed on 103 NSCLC tissues, and its associations with serum KL-6 levels and survival were examined. We also evaluated whether KL-6 expression patterns and/or serum KL-6 levels could predict prognosis in these NSCLC patients. Immunohistochemical analysis of KL-6 in NSCLC tissues showed that a depolarized KL-6 expression pattern was associated with a high level of circulating KL-6 and a poor prognosis in NSCLC patients who underwent curative surgery. Furthermore, a high circulating KL-6 level was associated with both poorer progression-free survival (PFS) and overall survival (OS), and multivariate analyses confirmed its independent prognostic value for both PFS and OS (p = 0.041 and 0.023, respectively). Our data suggest that preoperative serum KL-6 level reflects KL-6 expression patterns in NSCLC tissue, and can serve as a useful prognostic biomarker in NSCLC patients who undergo curative surgery.
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Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/cirugía , Mucina-1/sangre , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Inmunohistoquímica , Masculino , Ratones , Persona de Mediana Edad , Pronóstico , Resultado del TratamientoRESUMEN
In the present study, malignant mesothelioma (MM) cases in Japan were investigated retrospectively. We extracted records for 6030 cases of death due to MM between 2003 and 2008 to clarify the clinical features of MM, including its association with asbestos exposure (AE). Of all these cases, a clinical diagnosis of MM was confirmed for 929. The origin of MM included the pleura in 794 cases (85.5%), the peritoneum in 123 cases (13.2%), the pericardium in seven cases (0.8%), and the testicular tunica vaginalis in five cases (0.5%). The histological subtypes of MM included 396 epithelioid (55.9%), 154 sarcomatoid (21.7%), 126 biphasic (17.8%), and 33 cases (4.7%) classified as "other types". Of all the MM cases, AE was indicated in 76.8% and pleural plaques were detected in 34.2%. The number of asbestos particles was determined in 103 cases of MM. More than 1000 asbestos particles per gram dried lung tissue were detected in 74.8% of cases and more than 5000 particles were detected in 43.7% of cases. We compared patient characteristics and the diagnostic procedures for MM before and after the "Kubota shock". Compared with the early phase of this study (2003-2005), the median age at diagnosis of MM was higher, the number of cases without definite diagnosis of MM was lower, the proportion of cases diagnosed by thoracoscopy was higher, and the percentage of cases in which the occupational history was described in the medical records was significantly higher in the later phase (2006-2008). Our study confirmed that more than 70% of MM cases in Japan are associated with AE. The "Kubota shock" may affect some features pertaining to MM.
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Amianto/efectos adversos , Mesotelioma/inducido químicamente , Mesotelioma/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón/epidemiología , Masculino , Mesotelioma/patología , Persona de Mediana Edad , Adulto JovenRESUMEN
Mesothelioma, a highly aggressive cancer with poor prognosis and refractory to currently available therapies show increasing trends of its incidence in Japan and other developing countries. Although surgery is a gold standard for patients with early mesothelioma, most patients with advanced disease are not suitable for surgical resection and have option of palliative chemotherapy alone. One of the new treatment strategies for mesothelioma, the humanized anti-CD26 monoclonal antibody therapy is under development. CD26, a 110-kDa transmembrane glycoprotein with known dipeptidyl peptidase IV activity, plays a role in tumor development and its expression was reported in various human malignancies. This study determined the preliminary selection criteria for humanized monoclonal anti-CD26 antibody therapy. Eighty-one epithelioid (49 differentiated and 32 less differentiated), 34 sarcomatoid, 19 biphasic mesothelioma and 8 mesothelioma cell lines were immunohistochemically examined using 8 different commercially available anti-CD26 antibodies for membranous and cytoplasmic expression. The cytoplasmic expression of CD26 was observed in all histological types of mesothelioma, while the membranous expression of CD26 was found in 88% of differentiated and 69% of less differentiated epithelioid mesothelioma, and none of sarcomatoid mesothelioma with anti-CD26 antibodies with rabbit polyclonal anti-DPP4 antibody and similar results were also obtained with goat polyclonal anti-DPP4/CD26 antibody. These antibodies absorbed with soluble human CD26 proteins do not show CD26 expression in mesothelioma tissue, suggesting these two antibodies localize true CD26 protein. Seven mesothelioma cell lines, including sarcomatoid types, also showed membranous expression of CD26 in cellblock preparation. CD26 vector transfection to CD26-negative MSTO-211H cells showed membranous expression of CD26 by flow cytometry, but not in tumor developed in NOD/SCID mice with inoculation of CD26 vector transfected MSTO-211H cells. We found that both rabbit and goat polyclonal antibodies are suitable for immunohistochemical evaluation of membranous expression of CD26 in mesothelioma.
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Membrana Celular/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Expresión Génica , Mesotelioma/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Dipeptidil Peptidasa 4/genética , Femenino , Humanos , Masculino , Mesotelioma/tratamiento farmacológico , Mesotelioma/patología , Ratones , Ratones SCID , Persona de Mediana Edad , Trasplante de Neoplasias , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Adulto JovenRESUMEN
To examine the radiofrequency ablation (RFA) reliability in early breast cancer, we performed RFA followed by delayed surgical resection on 41 patients with invasive or non-invasive breast carcinoma less than 2 cm. MRI scans were obtained before ablation and resection. Excised specimens were examined pathologically by haematoxylin-eosin and nicotinamide adenine dinucleotide-diaphorase staining. 40 patients completed 1 RFA session, which was sufficient to achieve complete tumour cell death. Overall complete ablation rate was 87.8% (36/41). There were no treatment-related complications other than that of a superficial burn in 1 case. After RFA, the tumour was no longer enhanced on MRI in 25/26 (96.2%) cases. Residual cancer, which was suspected on MRI in 1 case, was confirmed pathologically. MRI could be an applicable modality to evaluate therapeutic effect. RFA could be an alternate local treatment option to breast-conserving surgery for early breast cancer.
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Neoplasias de la Mama/cirugía , Ablación por Catéter , Mastectomía Segmentaria , Procedimientos Quirúrgicos Mínimamente Invasivos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Estudios de Factibilidad , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Invasividad Neoplásica , Proyectos Piloto , Factores de Tiempo , Resultado del TratamientoRESUMEN
By the radiological examination, differential diagnosis of asbestosis from chronic interstitial pneumonia such as IPF/UIP is difficult. The pathological features of asbestosis show the peribronchiolar fibrosis which suggest that asbestos fibers cause the inflammation of bronchioli. Therefore, the criteria for pathological diagnosis of asbestosis in 2010, contain the finding of peribronchiolar fibrosis again. Chest CT scanning including HRCT for total of 38 cases clinically diagnosed asbestosis were reviewed by 3 radiologists and one pulmonologist. On the other hand, the histology of lung tissues obtained by surgery or autopsy were examined by 4 pulmonological pathologists. Furthermore, the content of asbestos bodies in the lung was counted by phase-contrast microscopy. Thirteen cases were definitely diagnosed of asbestosis in the image including HRCT and 17 cases were diagnosed by the histopathological examination showing lung fibrosis with peribronchiolar fibrosis. Only 10 cases were indicated asbestosis by both the radiological and histopathological examinations. The mean value of asbestos bodies for these cases, was 2,133,255 per gram of dry lung tissue.