Kang Hyeon Choe

EGFR Mutation Status in Primary Lung Adenocarcinomas and Corresponding Metastatic Lesions: Discordance in Pleural Metastases

UNLABELLED We evaluated EGFR and KRAS mutations between 37 paired primary tumors and corresponding metastases in lung adenocarcinoma. A substantial discordance was found in EGFR mutation status between primary tumors and corresponding metastases including pleural metastases. Moreover, the responsiveness to EGFR tyrosine kinase inhibitors tend to be correlated with EGFR mutation status in metastatic lesions than in primary tumors. INTRODUCTION The aim of this study was to compare epidermal growth factor receptor (EGFR) and KRAS mutations between primary tumors and corresponding metastases including pleural metastases in lung adenocarcinoma. METHODS Thirty-seven paired primary lung adenocarcinomas and corresponding metastatic tumors were analyzed for EGFR and KRAS mutations. In addition, 21 pleural metastases including malignant pleural effusion or pleural biopsy were used in performing these mutation analyses. RESULTS EGFR mutations were detected in 18 primary lung adenocarcinomas (48.6%) and in 16 corresponding metastases (43.2%). EGFR mutations showed a discordance rate of 16.2% (6 of 37 patients) between primary lung adenocarcinomas and corresponding metastases. Among 21 pleural metastases, 3 patients (14.3%) showed that the EGFR mutation was discordant. KRAS mutations were detected in one primary tumor and in two metastatic tumors. Eighteen patients were treated with EGFR tyrosine kinase inhibitors. One of seven patients who experienced partial response had EGFR mutations only in the metastasis, and two of seven patients who experienced progressive disease carried wild-type EGFR only in the metastasis. CONCLUSIONS EGFR mutations were discordant between primary tumors and corresponding metastases in a significant portion of lung adenocarcinomas. Furthermore, these discordance was also observed in metastases to the pleura, the nearest metastatic site.

Detection of EGFR Mutation Status in Lung Adenocarcinoma Specimens with Different Proportions of Tumor Cells Using Two Methods of Differential Sensitivity

Introduction: To evaluate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods with different sensitivities. Methods: EGFR mutation status was determined by peptide nucleic acid (PNA) clamping and direct sequencing. The samples consisted of 41 cell blocks of malignant pleural effusions with various proportions of tumor cells, as well as 23 lung biopsy specimens containing more than 20% tumor cells and the corresponding surgically resected tumors. Results: In the analysis of malignant pleural effusions, EGFR mutations were detected only by PNA clamping in four of nine patients who exhibited partial response to EGFR tyrosine kinase inhibitors; all the cell blocks of these four patients contained less than 20% tumor cells. Direct sequencing revealed wild-type EGFR, whereas PNA clamping revealed mutant EGFR, in one of five patients who exhibited progressive disease in response to EGFR tyrosine kinase inhibitor; the cell block of this patient contained a high proportion of tumor cells. A comparison of biopsy specimens containing sufficient tumor cells and the corresponding surgically resected tumors revealed discordance in the EGFR mutation status in four patients based on PNA clamping, whereas no discrepancies were observed by direct sequencing. Conclusions: Highly sensitive methods, such as PNA clamping, may be superior to direct sequencing for the detection of EGFR mutations in diagnostic specimens with a low proportion of tumor cells. Direct sequencing may be more representative when diagnostic specimens with a high proportion of tumor cells are available.

Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion

Purpose The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE). Materials and Methods Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA). Results The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%. Conclusion The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.

The diagnostic efficacy and safety of endobronchial ultrasound-guided transbronchial needle aspiration as an initial diagnostic tool

Background/Aims Real-time, convex probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used for the staging of malignant mediastinal lymph nodes. We evaluated the diagnostic efficacy and safety of EBUS-TBNA when used as an initial diagnostic tool. Methods We retrospectively studied 56 patients who underwent EBUS-TBNA as an initial diagnostic tool between August 2010 and December 2011. Procedure purpose were classified into four categories: 1) intrathoracic masses adjacent to the central airway; 2) enlarged lymph nodes for concurrent diagnosis and staging in suspected malignancy; 3) enlarged lymph nodes in suspected malignancy cases with inability to perform percutaneous core needle biopsy (PCNB); and 4) solely mediastinal masses/lymph nodes in lieu of mediastinoscopy. Results The diagnostic accuracy of EBUS-TBNA regardless of procedure purpose was calculated to be 83.9%. Furthermore, the diagnostic accuracy of malignant disease was significantly higher than benign disease (93.9% vs. 70.6%, p < 0.001). The diagnostic accuracy of EBUS-TBNA for each disease is as follows: tuberculosis, 50%; sarcoidosis, 60%; aspergillosis, 100%; lung abscess, 100%; lung cancer, 93%; and lymphoma, 100%. There were minor complications in seven patients during the EBUS-TBNA procedure. The complications included mild hypoxia and bleeding. Conclusions In conclusion, EBUS-TBNA is a useful initial diagnostic tool for both benign and malignant diseases. EBUS-TBAN is also a very safe procedure and less invasive compared to mediastinoscopy or PCNB.

Bowel infarction due to intestinal mucormycosis in an immunocompetent patient

Mucormycosis is a fatal opportunistic fungal infection that typically occurs in immunocompromised patients. The classical manifestation of mucormycosis is a rhinocerebral infection, and although primary gastrointestinal infection is uncommon, it has an extremely high mortality rate in immunocompromised patients. Furthermore, cases of gastrointestinal mucormycosis in an immunocompetent host are rarely reported. Here, we describe our experience of a male patient, with no underlying disease, who succumbed to a bowel infarction caused by intestinal mucormycosis during mechanical ventilatory care for severe pneumonia and septic shock.

Extranodal Interdigitating Dendritic Cell Sarcoma Presenting in the Pleura: A Case Report

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from the antigen-presenting cells of the immune system. This disease usually involves the lymph nodes, and rarely, extranodal sites may be affected. The authors report a case of extranodal IDCS presenting in the pleura. A 32-yr-old man presented with progressive chest pain. Imaging studies showed diffuse pleural thickening with pleural effusion. Morphological and immunohistochemical analysis of an incisional biopsy of the pleura were consistent with a diagnosis of IDCS; tumor cells were positive for S100 and CD45, but negative for CD1a, CD21, CD35, B cell and T cell markers. The patient was administered chemotherapy, but died of progressive disease. Although its incidence is extremely rare, this case suggests that extranodal IDCS should be considered in the differential diagnosis of undifferentiated neoplasms and that immunohistochemical staining be performed using appropriate markers.

Diagnostic performance of CD66c in lung adenocarcinoma-associated malignant pleural effusion: comparison with CEA, CA 19-9, and CYFRA 21-1.

Summary Various tumour markers have been evaluated in malignant pleural effusions, but not CD66c. This study evaluated the diagnostic ability of CD66c in lung adenocarcinoma-associated malignant pleural effusions (LA-MPEs) and compared it with other known tumour markers. Forty-seven cases of LA-MPE and 52 cases of benign pleural effusions were collected. The levels of CD66c, CEA, CA 19-9, and CYFRA 21-1 were measured by enzyme immunoassay. The expression of CD66c, CEA, and CA 19-9 in cell blocks was measured by immunocytochemistry. CEA had the best diagnostic values, with a sensitivity of 87.2% and specificity of 92.3%. Both CD66c and CA 19-9 showed the highest specificity of 98.1%, with sensitivities of 63.8% and 55.3%, respectively. CYFRA 21-1 had a sensitivity of 83.0% and specificity of 76.9%. CEA combined with CA 19-9 reached a sensitivity of 91.5% and a specificity of 98.1%. The sensitivities of immunocytochemical staining for CD66c, CEA, and CA 19-9 were 72.5%, 75%, and 40%, respectively. CD66c showed a diagnostic performance comparable to CYFRA 21-1 and CA 19-9 by enzyme immunoassay. Immunocytochemical study showed that CD66c and CEA were more sensitive than CA19-9. Both studies support CD66c as a potential tumour marker to differentiate LA-MPE from benign effusions.

The Prognostic Value of Residual Volume/Total Lung Capacity in Patients with Chronic Obstructive Pulmonary Disease.

The prognostic role of resting pulmonary hyperinflation as measured by residual volume (RV)/total lung capacity (TLC) in chronic obstructive pulmonary disease (COPD) remains poorly understood. Therefore, this study aimed to identify the factors related to resting pulmonary hyperinflation in COPD and to determine whether resting pulmonary hyperinflation is a prognostic factor in COPD. In total, 353 patients with COPD in the Korean Obstructive Lung Disease cohort recruited from 16 hospitals were enrolled. Resting pulmonary hyperinflation was defined as RV/TLC ≥ 40%. Multivariate logistic regression analysis demonstrated that older age (P = 0.001), lower forced expiratory volume in 1 second (FEV1) (P < 0.001), higher St. George Respiratory Questionnaire (SGRQ) score (P = 0.019), and higher emphysema index (P = 0.010) were associated independently with resting hyperinflation. Multivariate Cox regression model that included age, gender, dyspnea scale, SGRQ, RV/TLC, and 6-min walking distance revealed that an older age (HR = 1.07, P = 0.027), a higher RV/TLC (HR = 1.04, P = 0.025), and a shorter 6-min walking distance (HR = 0.99, P < 0.001) were independent predictors of all-cause mortality. Our data showed that older age, higher emphysema index, higher SGRQ score, and lower FEV1 were associated independently with resting pulmonary hyperinflation in COPD. RV/TLC is an independent risk factor for all-cause mortality in COPD. Graphical Abstract

Clinical investigation of cavitary tuberculosis and tuberculous pneumonia.

Background The radiographic characteristics of tuberculous pneumonia in adults are similar to primary tuberculosis that occurs in childhood, and upper lobe cavitary tuberculosis is the hallmark of postprimary tuberculosis. The purpose of this study was to investigate the factors associated with tuberculous pneumonia by making comparison with cavitary tuberculosis. Methods The medical records and radiographic findings of patients with cavitary tuberculosis and tuberculous pneumonia, and who were diagnosed between March 2003 and February 2006, were analyzed retrospectively. Results Forty patients had cavitary tuberculosis and sixteen patients had tuberculous pneumonia. Fever was more frequent for tuberculous pneumonia, whereas hemoptysis was more frequent for cavitary tuberculosis. The duration of symptoms before visiting the hospital was shorter, but the diagnosis after admission was more delayed for tuberculous pneumonia patients than for cavitary tuberculosis patients. The prevalence of underlying comorbidities such cancer, diabetes, alcoholism and long-term steroid use was not different between the two groups. The patients with tuberculous pneumonia were older and they had lower levels of serum albumin and hemoglobin than those with cavitary tuberculosis. The patients with tuberculous pneumonia showed a tendency to have more frequent endobronchial lesion. Tuberculous pneumonia occurred in any lobe, whereas the majority of cavitary tuberculosis patients had upper lung lesion, but the prevalence of lymphadenopathy, pleural effusion and previous tuberculosis scar was not different between the two groups. Conclusions Older age, a lower level of serum albumin and hemoglobin and a random distribution of lesion were associated with tuberculosis pneumonia as compared with cavitary tuberculosis. These findings suggest that the pathogenesis of tuberculous pneumonia might be different from that of cavitary tuberculosis.

Goodness-of-Fits of the Spirometric Reference Values for Koreans and USA Caucasians to Spirometry Data from Residents of a Region within Chungbuk Province.

Background Korean regression models for spirometric reference values are different from those of Americans. Using spirometry results of Korean adults, goodness-of-fits of the Korean and the USA Caucasian regression models for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were compared. Methods The number of study participants was 2,360 (1,124 males and 1,236 females). Spirometry was performed under the guidelines of the American Thoracic Society and the European Respiratory Society. After excluding unsuitable participants, spirometric data for 729 individuals (105 males and 624 females) was included in the statistical analysis. The estimated FVC and FEV1 values were compared with those measured. Goodness-of-fits for Korean and USA Caucasian models were compared using an F-test. Results In males, the expected values of FVC and FEV1 using the Korean model were 12.5% and 5.7% greater than those measured, respectively. The corresponding values for the USA Caucasian model were 3.5% and 0.6%. In females, the difference in FVC and FEV1 were 13.5% and 7.7% for the Korean model, and 6.3% and 0.4% for the USA model, respectively. Goodness-of-fit for the Korean model regarding FVC was not good to the study population, but the Korean regression model for FEV1, and the USA Caucasian models for FVC and FEV1 showed good fits to the measured data. Conclusion These results suggest that the USA Caucasian model correlates better to the measured data than the Korean model. Using reference values derived from the Korean model can lead to an overestimation regarding the prevalence of abnormal lung function.