[Show abstract][Hide abstract] ABSTRACT: There have been several epidemiologic studies about the association between 25(OH)D level and lung cancer risk. We explored the potential association between serum 25-hydroxyvitamin D [25(OH)D] levels and mutations in epidermal growth factor receptor (EGFR) in patients with pulmonary adenocarcinoma. We analyzed clinical data from 135 patients whose serum 25(OH)D levels were measured and EGFR mutational status was tested at the time of diagnosis. The relationship between 25(OH)D and clinical factors such as EGFR mutational status and sex was examined. The median serum 25(OH)D level in patients with pulmonary adenocarcinoma was 16.8 ng/ml (range: 3.0 - 84.3 ng/ml). 25(OH)D level was lower in female patients than male patients (p = 0.03). Of interest, 25(OH)D level of patients with EGFR mutated tumors was low compared with those with wild type (median 18.2 ng/ml vs. 14.7 ng/ml, p = 0.011). After a dose response relationship between EGFR mutations and 25(OH)D levels (as a continuous variable) was observed (OR = 0.96, p = 0.036), we categorized 25(OH)D levels into low (≤ 16.8ng/ml) vs. high (>16.8ng/ml). Multivariate analysis revealed the association between low 25(OH)D levels and high incidence of EGFR mutations (adjusted OR = 2.42, 95% CI: 1.11-5.26, p = 0.026). This study suggests that low 25(OH)D levels are associated with EGFR mutations in pulmonary adenocarcinoma.
Preview · Article · Jul 2014 · Endocrine Related Cancer
[Show abstract][Hide abstract] ABSTRACT: This study aimed to explore the potential association of mutation in the epidermal growth factor receptor (EGFR) with brain metastases in patients with pulmonary adenocarcinoma.
We analyzed clinical data on 314 patients who were tested for EGFR mutation and underwent brain magnetic resonance imaging at diagnosis. The relationship between EGFR mutation status and brain metastases at the initial presentation was analyzed. In addition, prognostic significance of EGFR mutational status on the risk of brain metastasis was evaluated in subgroups of surgically treated patients.
Of the 314 patients, 138 patients (43.9%) had EGFR mutations. The frequency of EGFR mutation was statistically higher for patients with brain metastases (64.7%, brain metastases; 39.8%, no metastases; 40.2%, extracranial metastases; p = 0.005). A strong association between EGFR mutation status and brain metastasis was observed (adjusted odds ratio = 3.83, p = 0.001), whereas no association was observed between EGFR mutation status and extracranial metastases (adjusted odds ratio = 1.73, p = 0.079). In addition, the number of brain metastases was significantly correlated with the EGFR mutation status (p = 0.029). Further analysis of 133 patients treated with surgical resection showed that EGFR mutation status was a poor prognostic factor for the risk of brain metastasis (hazard ratio = 4.49, p = 0.026) after adjustment for pathologic N stage.
We found a significant association between EGFR mutation and risk of brain metastases at the time of diagnosis and follow-up after curative resection for pulmonary adenocarcinoma. This result indicates the distinct clinical features of EGFR-mutated tumors in terms of brain metastases.
No preview · Article · Feb 2014 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to evaluate whether or not tumor spread and the diagnostic process in non-small cell lung cancer (NSCLC) is different based on smoking history.
Associations between smoking status and clinical presentation were evaluated controlling for the effect of histology. Lung cancer with delayed diagnosis (LCDD) and incidental detection (LCID) were determined based on medical records.
Of 914 patients, frequency of distant metastases was more common in never-smokers than in smokers (59% and 36%, respectively; P<0.001). Although never-smokers were more likely to have LCDD than smokers (18% and 11%, respectively; P=0.038), LCDD were not significantly associated with frequency of distant metastases [49% (LCDD) vs. 42% (non-LCDD); P=0.189] as well as tumor [29% (T3-4) vs. 24% (T1-2); P=0.134] and node [43% (N2-3) vs. 44% (N0-1); P=0.838] stage. Interestingly, never-smokers are more likely to have LCID than smokers (31% and 19%, respectively; P=0.010). In survival analysis, LCID (P=0.001; HR, 0.63) remained a prognostic factor, while LCDD did not.
This study suggests distinct metastatic pattern and diagnostic processes of never-smokers. The link between survival and incidental detection was also indicated.
No preview · Article · Dec 2013 · Journal of Thoracic Disease
[Show abstract][Hide abstract] ABSTRACT: Malignant epithelioid hemangioendothelioma (MEHE) is a rare vascular tumor with a biological behavior that lies between those of classical epithelioid hemangioendothelioma and angiosarcoma. Furthermore, MEHE is rarely diagnosed by fine needle aspiration cytology. The authors describe the cytological features of MEHE in a 41-year-old man who presented with increasing dyspnea over a period of 1 month before admission. Computed tomography of the chest showed a 3 cm poorly defined mass in the right lower lobe. Fine needle aspiration cytology demonstrated cellular smears of loosely cohesive clusters of epithelioid cells with numerous intracytoplasmic lumens in a necrotic background. Cellular features included fine chromatin and vesicular or slightly hyperchromatic nuclei with inconspicuous nucleoli and intranuclear inclusions. Nuclear membranes were relatively irregular with indentation. Mean N/C ratio was not increased, presumably due to a moderate amount of cytoplasm. The histologic examination displayed epithelioid and spindle cell proliferation with necrosis accompanying a classical epithelioid hemangioendotheliomatous area. The immunohistochemical evaluation was confirmatory and showed immunoreactivity for vascular markers. The authors also reviewed FNAB findings of epithelioid angiosarcoma, primary adenocarcinoma, and bronchioloalveolar carcinoma of the lung to identify cytomorphologic differences by literature bases. MEHE of the lung is difficult to diagnose cytologically because of its rarity and its cytomorphologic similarities with other malignant epithelial and mesenchymal tumors. However, it may be possible to distinguish it from other entities when the possibility of this unusual vascular neoplasm is suspected and ancillary studies are supportive.
No preview · Article · Nov 2011 · Diagnostic Cytopathology
[Show abstract][Hide abstract] ABSTRACT: Well-differentiated papillary mesothelioma (WDPM) is a rare subtype of malignant mesothelioma, which is considered to have low malignant potential. Because of its rare occurrence in the pleura, cytopathologists are not familiar with the cytologic features of WDPM, and to date only one report regarding the cytomorphology of aspiration biopsies of WDPM in pleura has been released. The authors present the findings of fine needle aspiration cytology of WDPM in the pleura in a 53-year-old woman. Aspiration smears showed papillary clusters composed of one to three layers of surface tumor cells and a central hyalinized stromal core. Tumor cells were round, ovoid, and spindle like with minimally atypical nuclei and small conspicuous nucleoli. Mitotic activity was virtually absent. Excisional biopsy histologic and immunohistochemical findings were wholly compatible with WDPM findings. Knowledge of the specific cytologic findings of WDPM is crucial for accurate diagnosis and appropriate treatment.
Preview · Article · Dec 2009 · The Korean Journal of Pathology
[Show abstract][Hide abstract] ABSTRACT: This retrospective study was performed to evaluate a possible association between the presence of epidermal growth factor receptor (EGFR) mutations and the standardized uptake value (SUV) of (18)F-fluoro-2-deoxy-glucose ((18)F-FDG) uptake in patients with non-small cell lung cancer (NSCLC). We included 100 patients who were tested for EGFR mutations by direct sequencing of resected tissues and who underwent preoperative positron emission tomography/computed tomography at the time of diagnosis. The maximum SUV by the primary tumor was chosen for further analysis. EGFR mutations in exons 19 and 21 were detected in 21 NSCLC patients (21%). EGFR mutations were more frequent in never-smokers than ever-smokers (35% versus 11%; P=0.003), in adenocarcinomas than non-adenocarcinomas (34% versus 6%; P=0.001), and in females than males (41% versus 12%; P=0.001). The SUV ranged from 1.3 to 33.0 (median 10.6). Area under receiver operating characteristic curve for SUVs in respect to the presence of EGFR mutations was 0.74 (95% CI: 0.62-0.85). When a cut off value was used, patients with low SUVs were more likely to have EGFR mutations than those with high SUVs (40% versus 11%; P=0.001). On multivariate analysis, a low SUV remained a significant predictors for EGFR mutations (P=0.025). (18)F-FDG uptake was associated with the presence of EGFR mutation. These results extrapolate that (18)F-FDG uptake might be helpful to discriminate patients who harbor EGFR mutations, especially when a genetic test is not feasible.
Full-text · Article · May 2009 · Lung cancer (Amsterdam, Netherlands)
[Show abstract][Hide abstract] ABSTRACT: We aimed to discriminate subgroups according to the risk of brain metastases in patients with non-small cell lung cancer (NSCLC) lacking neurological symptoms. We performed a retrospective review of 433 patients with NSCLC who underwent chest computed tomography (CT), brain magnetic resonance imaging (MRI) and bone scans at an initial staging work-up between April 2003 and April 2007. Brain metastases were determined by MRI. Patients were stratified into groups according to the number of risk factors (0-3) identified by multivariate analysis. In multivariate analysis, histopathology with non-squamous cell carcinoma, nodal stage 2 on CT and presence of bone metastases were three risk factors for brain metastases. Patients were divided into four groups according to the number (0-3) of these predictive factors. The proportions of patients with brain metastases in the four groups were 2%, 3%, 17% and 35%, respectively, and these differences were significant (P<0.001). When analysis was performed in patients with localised disease, the number of risk factors was correlated with the prevalence of brain metastases (P=0.013) but stage was not (P=0.153). Although this diagnostic model should be validated through further studies, our data suggest that the number of risk factors might be a useful tool to identify silent brain metastases in patients with NSCLC.
Full-text · Article · Aug 2008 · European journal of cancer (Oxford, England: 1990)
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the potential role of (18)F-fluoro-2-deoxy-glucose (FDG) uptake by primary tumors and N2 nodes on positron emission tomography (PET) in patients with stage IIIA N2 non-small-cell lung cancer (NSCLC). We retrospectively analyzed PET scans of 57 NSCLC patients who received surgical resection and proved pathologically to have stage IIIA N2 disease between January 2000 and April 2005. On each patient's PET scan, FDG uptake by the primary tumor and N2 nodes was evaluated using the maximum standardized uptake value (SUV). The SUV of the primary tumor (SUVt) and the highest value of the N2 nodes (SUVn) in each patient were treated as continuous variables for initial analysis. The SUVn and T stage (T1-2 vs. T3) were significant prognostic factors in univariate analysis (P=0.004 and 0.017, respectively), but the SUVt was not. Adjusted for the size of the N2 node (<or=1cm vs.>1cm), SUVt, and T stage (T1-2 vs. T3), the SUVn was associated with survival (P=0.019). Patients were divided into those with a low and high SUVn using a cutoff value. Controlling for the size of N2 nodes and T stages, patients with a low SUVn showed a tendency for prolonged survival (P=0.053). These results suggest that FDG uptake by the N2 node may predict survival of patients with stage IIIA N2 NSCLC.