• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.557-567
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• 2001

Background : Tumor angiogenesis is required for tumor growth and metastasis. In this study, we investigated the correlation between the intensity of angiogenesis and stage, nodal status, histologic type, metastasis and survival rate of non-small cell lung cancer. Method : Formalin fixed, paraffin embedded surgical specimens of 45 patients who had surgically resected primary non-small cell lung cancers without pre or post operative adjuvant chemotherapy or radiotherapy were examined. The microvessel count(MVC) was demonstrated by immunohistochemical staining for CD31(platelet endothelial cell adhesion molecule, PECAM). Results : Microvessel counts(MVCs) in stage IIIA and IIIB were higher than in stage I and II(p<0.05). The MVC in patients with lymph node metastasis was higher than that in patients without lymph node metastasis, although the difference was not statistically significant(p>0.05). However, in adenocarcinoma, the MVC in patients with lymph node metastasis was significantly higher than that seen in patients without lymph node metastasis(p<0.05). The MVC in adenocarcinoma was higher than that in squamous cell carcinoma(p<0.05). The difference between the MVCs of adenocarcinoma and squamous cell carcinoma was not statistically significant in stage I and II or N0 stage(p>0.05). However, in stage IIIA and IIIB or N1~3 stage, the MVC in adenocarcinoma was higher than that in squamous cell carcinoma(p<0.05). MVC was more increased when metastasis developed within 12 months. In the same histologic type and stage, the duration of survival time in patients with high MVC was shorter than in patients with low MVC, however the difference was not statistically significant(p>0.05). The survival rate in patients with high MVCs was lower than that in patients with low MVCs(P<0.05). Conclusion : In non-small cell lung cancer, MVC correlated relatively well with pathologic stage, nodal status(limited in patients with adenocarcinoma), histologic type, postoperative metastasis and survival rate. However, in the same histologic type and stage, MVC was not significantly related to the duration of survival. Therefore the assessment of the intensity of angiogenesis in non-small cell lung cancer may be helpful in predicting prognosis and in selecting patients for systemic adjuvant therapy of potential metastasis according to the results.

• The Korean Journal of Cytopathology
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• v.8 no.2
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• pp.109-114
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• 1997

Transbronchial fine needle aspiration(TBNA) is one of the cytologic methods in diagnosing lung cancers. TBNA can be used in cases of hilar, mediastinal or lung masses adjacent to the bronchi. We analyzed and compaired the findings of 27 cases of TBNA and bronchial washing and brushing(BW/BB) in lung cancers confirmed by either biopsy or surgical resection between Jun, 1996 and May, 1997 in Asan Medical Center. They were 18 cases of non-small cell carcinomas(eight squamous cell carcinomas, nine adenocarcinomas, and one large cell undifferentiated carcinoma), eight cases of small cell carcinomas, and one case of metastatic hepatocellular carcinoma. The sensitivity of TBNA was 37%(10/27) and false negative was 63%(17/27). Although the sensitivity of BW/BB w3s 56%(15/27), it was not different statistically from that of TBNA(Chi square, p=0.38). Overall sensitivity of TBNA and BW/BB in this series was 70%(19/27). Forty-seven percent of false negative TBNA(8/17) were positive in BW/BB. The findings suggest that the addition of TBNA to the standard BW/BB increases diagnostic yield in cytologic diagnosis of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.42-46
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• 2009

Lung cancer is one of the most prevalent cancers and it has the highest mortality of all forms of cancers. Although surgery, chemotherapy and radiotherapy are routinely used for the treatment of lung cancer treatment, little progress has been made in the treatment of this condition over the past 20 years. The histological subtype of squamous cell carcinoma (SCC) accounts for approximately 30% of all lung cancer patients. Spontaneous regression of non-small-cell lung cancer (NSCL) is an extremely rare phenomenon. Spontaneous regression of cancer (SR) is defined as a complete or partial, temporary or permanent disappearance of all or at least some the relevant parameters of soundly diagnosed malignant disease without any medical treatment or with treatment that is considered inadequate to produce the resulting regression.

• Tuberculosis and Respiratory Diseases
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• v.48 no.3
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• pp.324-330
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• 2000

Objective : Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. Multiple molecular changes and growth factor production have been documented in lung cancers, both small cell and non-small cell types. Insulin-like growth factors(IGFs) are important mitogenic and anabolic peptides, both in vivo and in vitro, and are thought to be significant autocrine-paracrine factors involved in normal and malignant cell proliferation. In this study, the degree of expression of IGF-1 on the immunohistochemical staining in human non-small cell lung cancer(NSCLC) cells and small cell lung cancer (SCLC) cells were investigated. Methods : Immunohistochemical staining for IGF-1 was performed in 15 cases of small cell carcinoma, 15 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 12 cases of bronchoalveolar carcinoma. Results : The expression of IGF-1 on the immunohistochemical staining significantly increased in NSCLC cells than in SCLC cells. Conclusion : These results suggest the expression of IGF-1 in human lung cancer cells. The immunohistochemical staining of IGF-1 in lung cancer cell lines may assist in the differentiation of NSCLC and SCLC.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.321-329
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• 2006

Background : To evaluate the clinical characteristics of lung cancer patients in Korea, where there is a higher number of smokers than in Western countries. Methods : A retrospective study was performed on 1655 lung cancer patients, who were diagnosed at a university hospital between September 1996 and August 2005. Age, gender, cell types and clinical stage were analysed. Of 941 patients, who responded to a questionnaire at the time of diagnosis, the smoking habits, occupational history, family history of lung cancer in the first-degree relatives, coexisting diseases (diabetes mellitus and cardiovascular disease), body weight loss, ECOG performance status and presenting symptoms, were examined prospectively. In addition, coexisting diseases including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and active pulmonary tuberculosis were evaluated. Results : Of the 1655 patients, the male to females ratio was 3.6. Squamous cell carcinoma was the most common cancer whereas adenocarcinoma was more common in lifetime nonsmokers or women. 19.9% of the patients were non smokers and 80.1% ever smokers. Since 2000, there was an increase in the incidence of adenocarcinoma with a corresponding decrease in the incidence of squamous cell carcinoma. 6.2% of patients were asymptomatic. A coincident diagnosis of chronic obstructive pulmonary disease, cardiovascular disease, diabetes mellitus, active pulmonary tuberculosis, and idiopathic pulmonary fibrosis was made in: 44.1%, 22.2%, 10.7%, 3.9%, and 1.6% of patients, respectively. A positive family history of lung cancer in the first-degree relatives was identified in 4.4% of patients. An occupational history relevant to lung cancer was identified in 12.2% of patients. Conclusion : There is a high proportion of cigarette smokers in Korean lung cancer patients. The most common cell type was squamous cell carcinoma. However, a more detailed, prospective study of the clinical characteristics will be needed to better characterize lung cancer in Korea.

• Journal of Life Science
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• v.21 no.3
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• pp.417-423
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• 2011

Thymosin ${\beta}4$ (TB-4) has been reported to play a key role in tumor growth, metastasis and angiogenesis. In addition, TB-4 induced the expression of vascular endothelial growth factor (VEGF) and stabilized the hypoxia-inducible factor (HIF)-$1{\alpha}$ in melanoma cells. Although the importance of thymosin ${\beta}4$ in angiogenesis and metastasis has been proven, there are few studies that show the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$. This study was conducted to analyze the relationship among these proteins in various tumors. Using tissue microarray analysis, we investigated the expression patterns of TB-4, VEGF and HIF-$1{\alpha}$ in various tumors to identify the expression patterns and relationships of these proteins in certain tumors. TB-4 was highly expressed in osteosarcoma, colon adenocarcinoma, esophageal squamous cell carcinoma, kidney and urinary bladder transitional carcinoma, lung cancer, and liver cancer. HIF-$1{\alpha}$ was highly expressed in nasal cavity inverted papilloma, lung cancer, and esophageal squamous cell carcinoma. The expression patterns of TB-4 and HIF-$1{\alpha}$ were almost similar and co-localized. VEGF expression was high in the blood vessels in tumors, but usually not high in the tumors themselves. VEGF was moderately expressed in stomach cancer, liver angiosarcoma, gall bladder adenocarcinoma, and uterus endometrial adenocarcinoma. The expression patterns of VEGF shows similarities in certain tumors including stomach cancer, osteosarcoma, liposarcoma, lung cancer, liver cancer, gall bladder adenocarcinoma, esophageal squamous cell carcinoma, stomach cancer, colorectal carcinoma and renal cell carcinoma. These results suggest that the expression patterns of TB-4, HIF-$1{\alpha}$ and VEGF were co-localized and related to tumorigenesis and angiogenesis of certain tumors.

• Tuberculosis and Respiratory Diseases
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• v.58 no.4
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• pp.352-358
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• 2005

Microsatellites are short tandem repeated nucleotide sequences that are present throughout the human genome. Variations in the repeat number or a loss of heterozygosity around the microsatellites have been termed a microsatellite alteration (MA). A MA reflects the genetic instability caused by an impairment in the DNA mismatch repair system and is suggested to be a novel tumorigenic mechanism. A number of studies have reported that MA in the DNA extracted from the plasma occurs at varying frequencies among patients with a non-small cell lung carcinoma (NSCLC). The genomic DNA from 9 subjects with a non-small cell lung cancer (squamous cell cancer 6, adenocarcinoma 2, non-small cell lung cancer1) and 9 age matched non-cancer control subjects (AMC: tuberculosis 3, other inflammatory lung disease 6) and 12 normal control subjects (NC) were extracted from the peripheral blood leukocytes and plasma. Three microsatellite loci were amplified with the primers targeting the Gene Bank sequence D21S1245, D3S1300, and D3S1234. MA in the form of an allelic loss or a band shift was examined with 6% polyacrylamide gel electrophoresis and silver staining. None (0/12) of the NC subjects less than 40 years of age showed a MA in any of the three markers, while 88.9%(8/9) of the AMC above 40 showed a MA in at least one of the three markers (p<0.05). Sixty percent(6/10) of the control subjects with a smoking history showed a MA in one of the three markers, while 9.1%(1/11) of the control subjects without smoking history showed a MA (p<0.05). However, not only did 66.7%(6/9) of lung cancer patients show a MA in at least one of the three markers but so did 88.9%(8/21) of the AMC patients (p>0.05). In conclusion, a MA in the D21S1245, D3S1300, and D3S1234 loci using DNA extracted from the plasma was detected in 66.7% of lung cancer while no MA was found in the young non-smoking control subjects. However, many of the non-cancer control subjects (aged smokers) also showed a MA, which compromised the specificity of the MA analysis as a screening test. Therefore, a further study with a larger sample size will be needed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9865-9869
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• 2014

Background: Transthoracic fine needle aspiration (FNA) is one of several methods for establishing tissue diagnosis of lung lesions. Other tissue or cell sources for diagnosis include sputum, endobronchial biopsy, washing and brushing, endobronchial FNA, transthoracic core needle biopsy, biopsy from thoracoscopy or thoracotomy. The purpose of this study was to compare the sensitivity and specificity of FNA and other diagnostic tests in diagnosing lung lesions. Materials and Methods: The population included all patients undergoing FNA for lung lesions at Meir Medical Center from 2006 through 2010. Information regarding additional tissue tests was derived from the electronic archives of the Department of Pathology, patient records and files from the Department of Oncology. Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values were calculated for each test. Results: FNA was carried out in 245 patients. Malignant tumors were diagnosed in 190 cases (78%). They included adenocarcinoma (43%), squamous cell carcinoma (15%), non-small cell carcinoma, not otherwise specified (19%), neurondocrine tumors (7%), metastases (9%) and lymphoma (3%). The specificity of FNA for lung neoplasms was 100%; sensitivity and diagnostic accuracy were 87%. Conclusions: FNA is the most sensitive procedure for establishing tissue diagnoses of lung cancer. Combination with core needle biopsy increases the sensitivity. Factors related to the lesion (nature, degenerative changes, location) and to performance of all stages of test affect the ability to establish a diagnosis.

• Korean Journal of Radiology
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• v.22 no.3
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• pp.464-475
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• 2021

Objective: This study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification. Materials and Methods: Among the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed. Results: The median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma. Conclusion: The tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification.

• Molecules and Cells
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• v.42 no.2
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• pp.161-165
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• 2019

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and has high rates of metastasis. Transforming growth factor beta-inducible protein (TGFBI) is an extracellular matrix component involved in tumour growth and metastasis. However, the exact role of TGFBI in NSCLC remains controversial. Gene silencing via DNA methylation of the promoter region is common in lung tumorigenesis and could thus be used for the development of molecular biomarkers. We analysed the methylation status of the TGFBI promoter in 138 NSCLC specimens via methylation-specific PCR and evaluated the correlation between TGFBI methylation and patient survival. TGFBI promoter methylation was detected in 25 (18.1%) of the tumours and was demonstrated to be associated with gene silencing. We observed no statistical correlation between TGFBI methylation and clinicopathological characteristics. Univariate and multivariate analyses showed that TGFBI methylation is significantly associated with poor survival outcomes in adenocarcinoma cases (adjusted hazard ratio = 2.88, 95% confidence interval = 1.19-6.99, P = 0.019), but not in squamous cell cases. Our findings suggest that methylation in the TGFBI promoter may be associated with pathogenesis of NSCLC and can be used as a predictive marker for lung adenocarcinoma prognosis. Further large-scale studies are needed to confirm these findings.