• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.36-43
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• 1999

Background : Tumor growth is the net result of intrinsic proliferation and escape from active cell death. bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death(apoptosis). Based on this information, it seems to be reasonable to expect that there may be clinical prognostic significance of bcl-2 expression in non-small cell lung cancer. But its prognostic significance is not established. Methods: To investigate the role of bcl-2 in lung cancer, we performed immunohistochemical stain of bcl-2 on 57 biopsy specimens from resected primary non-small cell lung cancer. Thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between bcl-2 expression, clinical parameters, S-, $G_1$-phase fraction and survival. Results: bcl-2 were detected in 43.8% of total 57 patients(according to histology, squamous cancer 47%, adenocarcinoma 32%, according to TNM stage, I 28.6%, II 52.3%, III 45.5%. both differences were insignificant). By using the flow cytometric analysis, mean S-phase fraction of bcl-2(+) and (-) group were 14.1($\pm7.8$)%, 24.7($\pm10.5$)% (p<0.005), mean $G_1$-phase fraction of bcl-2(+) and bcl-2(-) group were 75.5($\pm10.8$)%, 65.5($\pm11.4$)%(p<0.05). 2yr, 3yr and 5yr survival and median survival time of bcl-2(+) group were 65%, 54%, 41%, 53 months, and those of bcl-2(-) group were 71%, 52%, 46%, 37 months. (p>0.05, Kaplan-Meier, log rank) Conclusion: bcl-2 was detected in 43.8% of primary non-small cell lung cancer. The S-phase fraction of bcl-2(+) group was less than bcl-2(-) group, and G1-phase fraction of bcl-2(+) group was more than bcl-2(-) group. But, expression of bcl-2 could not be a prognostic factor.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.117-127
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• 2002

Backgroud : MUC1 mucin is a heavily glycosylated large glycoprotein and is expressed aberrantly in carcinoma. CD44 is polymorphic family of cell surface glycoproteins participating in cell-cell adhesion and modulation of the cell-matrix interaction. MUC1 mucin and CD44 expression have been implicated in a tumor invasion and metastasis in certain malignancies. In this study, the expression of MUC1 and the standard form of CD44 (CD44s) was examined in non-small cell lung cancer (NSCLC). Methods : Immunohistochemical staining using monoclonal antibodies including MUC1 glycoprotein and CD44s was performed on 80 NSCLC surgical specimens. The association between MUC1 and CD44s expression and the histological type and tumor stage was investigated. Results : Depolarized MUC1 expression in more than 10% of cancer cells was found in 12 (27.9%) out of 43 squamous cell carcinomas (SCCs) and 12 (32.4%) out of 37 adenocarcinomas (ACs). It was not associated with the tumor histological type and the TNM-stage in SCCs. Depolarized MUC1 expression correlated with the N-stage in ACs (p=0.036). CD44s was expressed in 36 (83.7%) out of 43 SCCs and 14 (37.8%) out of 37 ACs. Reduced CD44s expression correlated with the N-stage (p=0.031) and the TNM-stage (p=0.006) in SCCs. Conclusions : Depolarized MUC1 expression was related to the nodal stage in NSCLC adenocarcinoma. Reduced CD44s expression was related to nodal involvement and the TNM-stage in squamous cell carcinoma. This suggests that MUC1 and CD44s expression in NSCLC might play important roles in tumor progression and cap be used as prognostic variables.

• Journal of Chest Surgery
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• v.31 no.4
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• pp.362-368
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• 1998

The aim of this study was to evaluate a usefulness of serum SCC antigen in diagnosis or evaluation of therapeutic effect of lung cancer by investigation of the differences of SCC antigen concentration in lung mass according to TNM staging, and mass size of lung cancer. And the other aim was to know whether SCC antigen plays a role in infiltrative growth of lung cancer or not, comparing with concentration of epidermal growth factor receptor(EGFr) in tissue which is related with growth and differentiation of tumor cell. The results of this study were as follows. The concentration of SCC antigen in squamous cell carcinoma of lung(69${\pm}$25ng/ml) was higher than in unaffected lung tissue(34${\pm}$7ng /ml).(p＜0.05). The concentration of SCC antigen was higher in squamous cell carcinoma (69${\pm}$25ng/ml) than in adenocarcinoma (35${\pm}$25ng/ml) (p＜0.05), but the concentration of EGFr showed no any significant difference in both histological types. In small sized mass(＜3cm in diameter) the concentration of SCC antigen in central portion of tumor was higher than that of peripheral portion, whereas in large sized mass($\geq$5cm in diameter), the concentration of SCC antigen in peripheral portion of tumor was higher than that of central portion.(p＜0.05). The concentration of EGFr according to tumor size was not significantly different in central and peripheral portion of tumor. The concentration of SCC antigen according to TNM staging of lung cancer was that from central portion was higher in stage I, II, but that from peripheral portion was higher in stage III, IV (p＜0.05). The concentration of EGFr from central portion was higher in higher TNM stage(not significant) but that from peripheral portion shows no significant changes. In conclusion, the concentration of SCC antigen in tissue was higher in squamous cell carcinoma than in unaffected lung tissue or adenocarcinoma, and the concentration of SCC antigen increased according to tumor size or TNM staging like in serum level. so, serum SCC antigen is a useful tumor marker to diagnose or evaluate therapeutic effect of squamous cell carcinoma of lung. But further studies are necessary to confirm the relation of infiltrative growth in lung cancer and concentration of SCC antigen because there was a different pattern of regional tissue concentration of SCC antigen and EGFr

• Radiation Oncology Journal
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• v.5 no.2
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• pp.97-104
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• 1987

From January 1970 through December 1984, 15 patients with sinonasal Non-Hodgkin's lymphoma combined to the head and neck were treated by external irradiation.13 patients were stage It and 2 were stage IIE by Ann Arbor Classification. However, when using TNM system, 7 were locally advanced T3, T4 lesions. All patients had follow up from 3.7 to 16 years with the median follow-up of 8.5 years. The overall actuarial 5-year survival rates were $25\%,\;28\%$ for IE and $0\%$ for IIE. Total tumor dose varied from 40 to 68 Gy. $100\%$ complete response with a total tumor dose of more than 55 Gy and $73\%$ complete response with less than 55Gy. When the disease was staged using the TNM (AJC) system, the five-year disease free survival for T1 and T2 patients was $50\%$ as compared with $14\%$ for T3 and T4. Failure rate by stage was $33\%(2/6)$ for T1 and T2, $86\%(6/7)$ for T3 and T4, and $100\%$(2/2) for IIE. The results suggest that 1. Higher CR could be obtained with a total tuner dose of more than 55 Gy. 2. Use of TNM staging system is as important as Ann arbor in management of sinonasal NHL. 3. The addition of combination chemotherapy should be considered for T3, T4 and IIE the sinonasal Non-Hodgkin's lymphoma although the disease is limited to head and neck.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.114-119
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• 2006

Purpose: The purpose of this study is to determine whether it is possible to evaluate patients with pN2 or pN3 early gastric cancer (EGC) as being in an advanced stage before and during the operation. Materials and Methods: 4,430 patients underwent a gastrectomy for cancer from 1990 to 2003. Eight of the 552 patients with EGC included pN2 or pN3. The estimated clinical and surgical stage before and during the operation were compared to the pathological results, and a follow-up of progression was done. Results: The patients were evenly distributed among all age groups with seven men and one woman. The pre-operative estimate of T1 by CT was 25% (2/8). In the main, the cT stage was over estimated. The estimate of over N2 was 50% (4/8). One patient was preoperatively staged as la sT1 during operation was 57.1% (4/7), and the estimate of over N2 was 67% (4/6). Two patients were intraoperatively evaluated as Ia. Only one patient survived over 5 years, and the mean survival of these patients was 15 months $(95%\;Cl:\;0{\sim}35.5)$. Conclusion: It was generally possible to evaluate patients with EGC of over pN2 as being in an advanced stage before and during the operation. Although very rare (2/552, 0.04%), there were EGC patients whose stages were not predictable at all. Therefore, more precise preoperative and intraoperative staging methods are warranted.

• Journal of Chest Surgery
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• v.41 no.1
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• pp.68-73
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• 2008

Background: The presence of infiltrated mediastinal lymph nodes is a crucial factor for the prognosis of lung cancer. The aim of our study is to investigate the pattern of metastatic non-small cell lung cancer that spreads to the mediastinal lymph nodes, in relation to the primary tumor site, in patients who underwent major lung resection with complete mediastinal lymph node dissection. Material and Method: We retrospectively. studies 293 consecutive patients [mean age $63.0{\pm}8.3$ years (range $37{\sim}88$) and 220 males (75.1%)] who underwent major lung resection due to non-small cell lung cancer from January 1998 to December 2005. The primary tumor and lymph node status was classified according to the international TNM staging system reported by Mountain. The histologic type of the tumors was determined according to the WHO classification. Fisher's exact test was used; otherwise the chi-square test of independence was employed. A p-value < 0.05 was considered significant. Result: Lobectomy was carried out in 180 patients, bilobectomy in 50, sleeve lobectomy in 10 and pnemonectomy in 53. The pathologic report revealed 124 adenocarcinomas, 138 squamous-cell tumors, 14 adenosquamous tumors, 1 carcinoid tumor, 8 large cell carcinomas, 1 carcinosarcoma, 2 mucoepidermoid carcinomas and 5 undifferentiated tumors. The TNM stage was IA in 51 patients, IB in 98, IIB in 41, IIIA in 71, IIIB in 61 and IV in 6. 25.9 % of the 79 patients had N2 tumor. Most common infiltrated mediastinal lymph node was level No.4 in the right upper lobe, level No. 4 and 5 in the left upper lobe and level No. 7 in the other lobes, but no statistically significant difference was observed. Thirty-six patients (12.3%) presented with skip metastasis to the mediastinum. Conclusion: Mediastinal lymph node dissection is necessary for accurately determining the pTNM stage. It seems that there is no definite way that non-small cell lung cancer spreads to the lymphatics, in relation to the location of the primary cancer. Further, skip metastasis to the mediastinal lymph nodes was present in 12.3% of our patients.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.363-371
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• 1994

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 the 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 small lung cancer cell was assessed in 42 patients who died after receiving anticancer chemotherapy. Results: 1) Mean survival time of patients with small cell lung cancer was 190(${\pm}156$) days. Survival time were shortened, when TNM stage and PS scale were advanced. 2) Mean value of SPF of patients with small cell lung cancer was 27.4(${\pm}8.5$)%. SPF had nothing to do with advance of TNM stage and PS scale. 3) In each identical TNM stage, there were not statistic significance between SPF and survival times. 4) There was a tendency like that higher SPF, better chemotherapeutic response. Conclusion: We could not find statistic significance between SPF and survival times, but SPF was a good predictive factor for chemotherapeutic response.

• Journal of Chest Surgery
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• v.35 no.5
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• pp.392-396
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• 2002

Background: Video-thoracoscopy is known to be an useful method to provide accurate pre-resectional staging in patients with lung cancer in addition to the conventional radiologic studies and mediastinoscopy, for the pleural cavity is inspected directly and biopsy specimens call be obtained. This study is undertaken to evaluate how video-thoracoscopy can be used in deciding pre-resectional stage Material and Method: Video-thoracoscopy was performed in patients with lung cancer who were scheduled for surgical resection based on the radiologic staging and mediastinoscopic biopsy. 37 patients were included in this study. Pre-thoracoscopically 18 cases were in TNM stage 1, 7 in stage 2, and 12 in stage 3. Result: In 15 of 37 cases, video-thoracoscopy could not be performed effectively due to heavy adhesions in the pleural cavity, diaphragmatic and chest wall invasion of tumor and bulky tumor mass es. Mediastinal lymph nodes were positive postresectionally in 6 of these 15 cases. In 22 cases, video-thoracoscopy was performed as usual. Positive mediastinal lymph nodes were identified in 2 cases and exploratory thoracotomy was prevented. Surgical resection were carried out in remaining 20 cases and 5 cases among them had positive mediastinal lymph nodes. Conclusion: We believe that it is difficult to perform pre-thoracotorny video-thoracoscopy for all lung cancer patients for there were many cases that thoracoscory could not be undertaken doe to heavy adhesions in the pleural cavity, tumor involvement of the chest wall and/or diaphragm and bulky tumor mass. However we think it is helpful in preventing unnecessary exploratory thoracotomy for some patients with lung cancer whom pre-thoracotomy video-thoracoscopy was carried out.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.756-765
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• 1997

Background : To study the prognosis of patients with lung cancer, many investigators have reported the methods to detect cell proliferation in tissues including PCNA, thymidine autoradiography, flow cytometry and Ki-67. PCNA, also known as cyclin, is a cell related nuclear protein with 36KD intranuclear polypeptide that is maximally elevated in S phase of proliferating cells. In this study, PCNA was identified by paraffin-embedding tissue using immunohistochemistry which has an advantage of simplicity and maintenance of tissue architecture. The variation of PCNA expression is known to be related with proliferating fraction, histologic type, anatomic(TNM) stage, degree of cell differentiation, S-phase fraction and survival rate. We analyzed the correlation between PCNA expression and S-phase fraction, survival. Method : To investigate expression of PCNA in primary lung cancer, we used immunohistochemical stain to paraffin-embedded sections of 57 resected primary non-small cell lung cancer specimen and the results were analyzed according to the cell type, cell differentiation, TNM stage, S-phase fraction and survival. Results : PCNA expression was divided into five group according to degree of staging(-, +, ++, +++, ++++). Squamous cell type showed high positivity than in adenocarcinoma. Nonsignificant difference related to TNM stage was noticed. Nonsignificant difference related to degree of cell differentiation was noticed. S-phase fraction was increased with advance of PCNA positivity, but it could not reach the statistic significance. The 2 year survival rate and median survival time were -50% 13 months, +75% 41.3 months, ++73% 33.6 months, +++67% 29.0 months, ++++25% 9 months with statistic significance (P<0.05, Kaplan-Meier, generalized Wilcox). Conclusion : From this study, PCNA expression was high positive in squamous cell cancer. And, there was no relationship between PCNA positivity and TNM stage, cellular differentiation or S-phase fraction. But, the patients with high positive PCNA staining showed poor survival rate than the patients with lower positive PCNA staining (p<0.05). It was concluded that PCNA immunostaining is a simple and useful method for survival prediction in paraffin embedded tissue of non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.757-765
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• 2000

Background : Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count as a measure of tumor angiogenesis, has been significantly correlated with invasive and metastatic patterns in breast. prostate and cutaneous carcinomas. Materials and Methods : Fifty patients with curatively resected non-small cell lung cancer were evaluated. Tumor tissues embedded in paraffin block were stained by anti CD 31 (PECAM, platelet endothelial cellular adhesion molecule) using immunohistochemical method to assess microvessel count. Microvessels were counted in the most active areas of neovascularization(microscopy, 200$\times$). Results: 1) Mean microvessel count was 47.1$\pm$17.7(per 200$\times$field) in total 50 cases. 2) Mean microvessel count of adenocarcinoma (54.4$\pm$19.9) was significantly higher than that of squamous cancer (43.9$\pm$16.2) (p<0.05), but there were no relationship between microvessel count and TNM stages. 3) Median survival time, 2-year and 5-year survival rates of the low microvascular group (microvessel count<45, 22 cases) were 61 months, 80% and 40%, respectively, and those of the high microvascular group(microvessel count$\geq$45, 28 cases) were 46 months, 75% and 12%, respectively. As results, prognosis of low microvascular group is statistically significantly superior to that of the high microvascular group (p=0.0162, Kaplan-Meier, log-rank). Conclusion : Angiogenesis assessed by microvessel count can be used as one of the significant prognostic factors in non-small cell lung cancer.