• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.455-465
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• 1999

Background: Even though lung cancer has become a major cancer in Korea, national survey for lung cancer has not been available except several reports from individual hospitals. Methods: Korean Academy of Tuberculosis and Respiratory Diseases retrospectively investigated the characteristics of lung cancer diagnosed from January 1997 to December 1997 at general hospitals over 400 beds. Results: Among 3,794 patients, 76.8% are smokers and 89.8% of male patients are smokers. Squamous cell carcinoma is the leading type of lung cancer(44.7%) followed by adenocarcinoma(27.9%). Smoking rate in adenocarcinoma was significantly lower than in squamous cell carcinoma and small cell cancer. Cough is the most common symptom, however, 7.2% are asymptomatic. Bronchoscopic biopsy has a main role in the diagnosis of squamous cell carcinoma and small cell cancer but percutaneous needle biopsy has more important role in adenocarcinoma. Two-thirds of NSCLC patients were found in unresectable advanced stages. Conclusion: In contrast to other countries, squamous cell carcinoma is still the most frequent type of lung cancer. High proportions of smoker and advanced, unresectable lung cancer urge us to develop the program for cessation of smoking and early detection.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.149-155
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• 1995

Background: Cytokeratin 19 is 40KD acidic molecule whose distribution is restricted to simple or pseudo-stratified epithelia, such as the epithelial layer of the bronchial tree. Immunohistochemical study have shown that cytokeratin 19 is overexpressed in lung carcinoma tissue. An immunoradiometric assay, CYFRA 21-1 has been developed using two monoclonal antibody, BM 19-21 and KS 19-1, reactive to different epitopes on cytokeratin 19. We studied the diagnostic value of CYFRA 21-1 in lung cancer. Method: The serum CYFRA 21-1 level using immunoradiometric kit(ELSA-CYFRA 21-1) was measured in 54 patients who admit to Yeungnam University Hospital from April, 1993 to August, 1994. Lung cancer group was 39 primary lung cancer patients(19 patients with squamous cell carcinoma, 11 patients with adenocarcinoma and 9 patients with small cell carcinoma). Control group was 15 patients with non malignant lung diseases(8 patients with pulmonary tuberculosis, 3 patients with chronic obstructive pulmonary disease, 2 patients with pneumonia and 2 patients with chronic obstructive pulmonary disease combined with pulmonary tuberculosis). Results: The mean serum value of CYFRA 21-1 was $20.2{\pm}4.7ng/ml$ in squamous cell carcinoma, $7.2{\pm}1.6ng/ml$ in adenocarcinoma and $15.5{\pm}4.7ng/ml$ in non-small cell lung cancer. The serum value of CYFRA 21-1 in control group was $1.7{\pm}0.5ng/ml$. All of the serum values of 3 histologic types were significantly higher than that of control group(p<0.01). The serum value of CYFRA 21-1 of squamous cell carcinoma was significantly higher than that of adenocarcinoma(p <0.05). Serum value of CYFRA 21-1 in small cell lung cancer was $2.9{\pm}0.9ng/ml$ and not significantly different compared with control group. Using cut off value of 3.3ng/ml, sensitivity and specificity was 11.1%, 65.2% in small cell lung cancer, 70.0%, 62.5% in non-small cell lung cancer, 73.7%, 75% in squamous cell carcinoma and 63.6%, 78.9% in adenocarcinoma, respectively. Conclusion: The serum levels of CYFRA 21-1 may be useful in diagnosis of non-small cell lung carcinoma, especially in squamous cell carcinoma with its high specificity.

• Journal of Chest Surgery
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• v.30 no.4
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• pp.445-448
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• 1997

Percutaneous transthoracic fine needle biopsy has been widely used In the diagnosis of pulmonary lesions especially lung cancer. Onc of the rarest complication's is that malignant cells are implanted within the needle tract and developed a chest wall mass subsequently. Wc expcrlenccd a case of chest wall implantatio of lung cancer after percutaneous transthoracic floe needle biopsy. A 65-ycar old man had undergone bilobectomy (right upper lobe and right middle lobe)for squamous cell (·4rcinoma (TINOMO) of the lung. 60 days after percutaneous biopsy (48 days after operation), a tiny nodule (1 mm sized) was notcd at the right anterior chcst wall where the diagnostic fine needle biopsy had been performed before operation. This tiny mass was rapidly growing to 1.5 cm sized mass for 20 days. We carried out wide excision of chest wall mass and skin grafting, and confirmed squamous cell carcinoma histopathologically as same as the lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.165-172
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• 2007

Background: The pathogenesis of lung cancer includes the accumulation of multiple genetic abnormalities. The CREB-binding protein(CBP) is one of several transcriptional co-activators among various sequence-specific DNA-binding transcription factors. CBP is involved in a wide range of cellular activities, such as DNA repair, cell growth, differentiation, and apoptosis that are suspected of contributing to tumorigenesis. The goal of this study was to evaluate CBP expression in a series of human lung tissues containing normal epithelium, premalignant lesions(hyperplasia and dysplasia) and squamous cell carcinomas. Materials and Methods: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections by use of a monoclonal anti-CBP antibody. CBP expression was compared in samples from 120 patients with premalignant and malignant histological types including 20 metaplastic specimens, 40 dysplastic specimens, and 60 squamous cell carcinomas in the lung. Results: CBP expression was seen in 35% (7/20) of the metaplastic specimens. 65% (26/40) of the dysplastic specimens, and 70% (42/60) of the squamous cell carcinomas (p<0.05). According to celluar atypism, CBP expression was 50% (10/20) of the low-grade dysplastic specimens and 80% (16/20) of the high-grade dysplastic specimens(p <0.01). By cellular differentiation, CBP expression was seen in 95% (19/20) of the well differentiated squamous cell carcinomas, 85% (17/20) of the moderately differentiated carcinomas and 30% (6/20) of the poorly differentiated lesions (p <0.05). Conclusion: These results suggest that CBP may have an important role in malignant transformation of precancerous lung lesions and may be a marker for malignancy.

• 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 Chest Surgery
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• v.29 no.9
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• pp.1031-1035
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• 1996

International Ass ciation for the Study of Lung Cancer(IASLC) recommended the following classification of small cell lung carcinoma(SCLC) : (1) Small cell carcinoma (2) Mixed small cell/large cell carcinoma (3) Combined small cell carcinoma. Combined small cell carcinomas contain a squamous cell carcinoma or adenocarcinoma component. The prognostic significance of these elements is not known, but since the frequency and extent of non-small cell elements are considerably greater in posttherapy and autopsy tissues, it is possible that the non-SCLC elements are more resistant to therapy than the SCLC cells. Metaplasia & dysplasia of the bronchial surface epithelium are frequently observed in the bronchial biopsy specimens that contain small cell carcinoma of the lung. We report a case of combined small cell carcinoma with squamous element associated with microinvasive squamous cell carcinoma of the bronchial surface epithelium in 68 year old male patient, stage was IIIa. The two lesion are not connected n serial sections.

• Tuberculosis and Respiratory Diseases
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• v.50 no.6
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• pp.668-675
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• 2001

Background : Non-smalll lung cancer(NSCLC) develops as a result of the accumulation of multiple genetic abnormalities. Loss of heterozygosity(LOH) is one of the most frequent genetic alterations that is found in NSCLC, and the chromosomal regions that display a high rate of LOH are thought to harbor tumor suppressor genes(TSGs). This study was done to determine the frequency of LOH in 21q with the aim of identifying potential TSG loci. Method : Thirty-nine surgically resected NSCLCs were analysed. Patients peripheral lymphocytes were used as the source of the normal DNA. Five microsatellite Inarkers of 21q were used to study LOH : 21q21.1(D21S1432, and D21S1994); 21q21.2-21.3(D21S1442) ; 21q22.1(21S1445) ; and 21q22.2-22.3(D21S266). The fractional allelic loss(FAL) in a tumor was calculated as the ratio of the number of markers showing LOH to the number of informative markers. Result : LOH for at least one locus was detected in 21 of 39 tumors(53.8%). Among the 21 tumors with LOH, 5(21.8%) showed LOH at almost all informative loci. Although statistically not significant, LOH was found more frequently in squamous cell carcinomas(15 of 23, 65.2%) than in adenocarcinomas(6 of 16, 37.5%). In the squamous cell carcinomas the frequency of LOH was higher in stage II-III (80.0%) than in stage I (53.8%). The FAL value in squamous cell carcinomas($0.431{\pm}0.375$) was significantly higher than that found in adenocarcinomas($0.l92{\pm}0.276$). Conclusion : These results suggest that LOH on 21q may be involved in the development of NSCLC, and that TSG(s) that contribute to the pathogenesis of NSCLC may exist on 21q.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.846-854
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• 1995

Background: Cytokeratin 19 is a subunit of cytokeratin intermediate filament expressed in simple epithelia such as respiratory epithelial cells and their malignant counterparts. An immunoradiometric assay is available to detect a fragment of the cytokeratin, referred to as Cyfra 21-1 in the serum. This study was conducted to evaluate the clinical utility of this new marker in the diagnosis of lung cancer compared with established markers of squamous cell carcinoma antigen (SCC Ag) and carcino-embryonic antigen(CEA). In addition, we compared the diagnostic sensitivity and specificity of Cyfra 21-1 with those of SCC Ag in squamous cell carcinoma of the lung. We also measured the level of Cyfra 21-1 in the different stages of squamous cell carcinoma of the lung. Method: We measured Cyfra 21-1(ELSA-CYFRA 21-1), SCC Ag(ABBOTT SCC RIABEAD) and CEA(ELSA2-CEA) in 79 patients with primary lung cancer and in 78 persons as a comparison group including 32 patients with pulmonary tuberculosis, 23 patients with benign lung disease and 23 cases with healthy individual. Cyfra 21-1 is measured by a solid-phase immunoradiometric assay(CIS Bio International, France) based on the two-site sandwich method. SCC Ag is measured by a radioimmunoassay(Abbott Laboratories, USA). CEA is measured by a immunoradiometric assay(CIS Bio International, France). All data were expressed as the mean$\pm$standard deviation. Results: 1) The mean value of Cyfra 21-1 was $18.38{\pm}3.65\;ng/mL$ in the lung cancer and $1.l6{\pm}0.53\;ng/mL$ in the comparison group(p<0.0001). SCC Ag was $3.53{\pm}6.06\;ng/mL$ in the lung cancer and $1.19{\pm}0.5\;ng/mL$ in the comparison group(p<0.01). CEA was $35.03{\pm}13.9\;ng/mL$ in the lung cancer and $2.89{\pm}1.01\;ng/mL$ in the comparison group(p<0.0001). 2) Cyfra 21-1 level in squamous cell carcinoma($31.52{\pm}40.13\;ng/mL$) was higher than that in adenocarcinoma($2.41{\pm}1.34\;ng/mL$)(p<0.0001) and small cell carcinoma($2.15{\pm}2.05\;ng/mL$)(p=0.007). SCC Ag level in squamous cell carcinoma($5.1{\pm}7.68\;ng/mL$) was higher than that in adenocarcinoma($1.36{\pm}0.69\;ng/mL$)(p=0.009) and small cell carcinoma($1.1{\pm}0.24\;ng/mL$) (p=0.024). 3) The level of Cyfra 21-1 was not correlated with the progression of stage in squamous cell carcinoma of the lung. 4) Using the cut-off value of 3.3ng/mL, the diagnostic sensitivity of Cyfra 21-1 was 83% in squamous cell carcinoma, 22% in adenocarcinoma and 17% in small cell carcinoma. The sensitivity of SCC Ag and CEA were 39% and 20%, respectively in squamous cell carcinoma, 11% and 39% in adenocarcinoma, and 0% and 33% in small cell carcinoma. 5) Comparison of the receiver operating characteristics curves(ROC curve) for Cyfra 21-1, SCC Ag and CEA revealed that Cyfra 21-1 showed highest diagnostic sensitivity among them in the diagnosis of lung cancer. Conclusion: Cyfra 21-1 is thought to be a better tumor marker for the diagnosis of lung cancer than SCC Ag and CEA, especially in squamous cell carcinoma of the lung.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.265-272
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• 2004

Background : RASSF1A, which is one of tumor suppressor genes, is frequently inactivated by hypermethylation of the promoter region in a variety of human cancers, including lung cancer. This study was performed to investigate the association between RASSF1A methylation and the clinicopathological factors in patients with squamous cell carcinoma of the lung. Methods : Eighty-one samples from the patients with squamous cell carcinoma of lung were examined. The promoter methyation of RASSF1A was analyzed by methylation specific PCR and sequencing. Statistical analysis was made to examine the association between RASSF1A methylation and the clinicopathological parameters. Results : RASSF1A methylation was observed in 37.0 % (30 of 81) of the patients with squamous cell carcinoma of the lung. RASSF1A methylation was found to be associated with cellular differentiation(p=0.0097) and the overall survival(p=0.0635). However, there was no association between RASSF1A methylation and the other clinicopathological parameters, such as the pathological TNM stage, the recurrence rate, lymph node invasion and the amount of cigarettes smoked. Conclusion : RASSF1A methylation might be associated with a poor prognosis in patients with squamous carcinoma of the lung. A larger scale study is needed.

• Tuberculosis and Respiratory Diseases
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• v.40 no.6
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• pp.669-676
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• 1993

Background: DNA content analysis of human solid tumor is now widely performed by flow cytometric study. One of the most interesting and potentially important observation in this field is that proliferative activity(S-Phase fraction of cell cycle) may profoundly affect prognosis. Method: S-Phase fraction(SPF) have been measured by flow cytometric method using tumor cells isolated from paraffin embedded tissue. To evaluate the prognostic significance, SPF of squamous lung cancer cell was assessed in 21 patients who died without any specific treatment. Results: 1) Mean survival time of squamous lung cancer patients was 225(${\pm}162$) days. Survival time were shortened, when TNM stage and PS scale were advanced. 2) Mean value of SPF of squamous lung cancer patients was 23.4(${\pm}11.3$)%. SPF had nothing to do with advance of TNM stage and PS scale. 3) Mean survival time of high SPF group(more than 20% of cell proliferation cycle) and low SPF group were 153(${\pm}99$) days and 342(${\pm}180$) days(p<0.01). In each identical TNM stage and PS scale, there were also statistic significant differences in mean survival time between high and low SPF group. Conclusion: On multivariate analysis including TNM stage and performance status, SPF was the significant and independent prognostic factor in the primary squamous lung cancer patients group.