• Title/Summary/Keyword: Paraffin-embedded tissue

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The Correlation between TGF-beta 1 Blood Levels and the Formation of Bullae in Patients with Spontaneous Pneumothorax (자연 기흉 환자의 혈액 내 TGF-beta 1 Ligand 양과 폐 기포 형성과의 연관관계에 대한 연구)

  • Kim, Young-Sam;Kim, Kwang-Ho;Baek, Wan-Ki;Kim, Joung-Taek;Cha, Il-Kyu;Kim, Ji-Hye;Song, Sun-U;Choi, Mi-Sook
    • Journal of Chest Surgery
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    • v.43 no.4
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    • pp.394-398
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    • 2010
  • Background: The overexpression of transforming growth factor-beta 1 receptor II (TGF-${\beta}1$RII) and transforming growth factor-beta 1 (TGF-${\beta}1$) ligand may be involved in the formation of a bulla. In this study, we tested if serum TGF-${\beta}1$ ligand levels correlated with the expression level of TGF-${\beta}1$RII and TGF-${\beta}1$ in bullous tissues from patients with spontaneous pneumothorax. Material and Method: Bullous lung tissues and blood samples were obtained from 19 patients with spontaneous pneumothorax, 18 males and 1 female, aged 17 to 35 years old. The bullous tissues were obtained by video-assisted thoracic surgery (VATS), fixed in formalin, embedded in paraffin, and cut into $5{\sim}6{\mu}m$ thick slices. Sections were immunohistochemically stained with primary antibodies against TGF-${\beta}1$ or TGF-${\beta}1$RII, and serum levels of TGF-${\beta}1$ in patients and normal controls was measured by enzyme-linked immunosorbent assay (ELISA). Result: Of the 19 patients, 16 were TGF-${\beta}1$ positive and 10 were TGF-${\beta}1$RII positive. Among the 16 TGF-${\beta}1$ positives, 9 were also TGF-${\beta}1RII$ positive. As seen previously, strong immunohistochemical staining of TGF-${\beta}1$RII and TGF-${\beta}$ was detected in the boundary region between the bullous and normal lung tissues. Average TGF-${\beta}1$ blood levels of both TGF-${\beta}1$ and TGF-${\beta}1$RII positive patients was $38.36{\pm}16.2ng/mL$, and that of five controls was $54.06{\pm}15ng/mL$. Conclusion: These results suggest that overexpression of TGF-${\beta}1$ and TGF-${\beta}1$RII expression may be involved in the formation of bullae. TGF-${\beta}1$ blood levels in patients with primary spontaneous pneumothorax is lower than normal people, suggesting that the high level of local TGF-${\beta}1$ expression in the bullous tissue region, but not in the whole blood, may contribute more in the formation of bullae.

Is the BRCA Germline Mutation a Prognostic Factor in Korean Patients with Early-onset Breast Carcinomas? (한국의 젊은 여성유방암 환자에서 BRCA 배선유전자 돌연변이는 예후인자인가?)

  • Choi Doo Ho;Lee Min Hyuk;Haffty Bruce G.
    • Radiation Oncology Journal
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    • v.21 no.2
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    • pp.149-157
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    • 2003
  • Purpose: The purpose of this study was to determine if there were prognostic differences between BRCA related and BRCA non-related Korean patients with early-onset breast carcinomas. Materials and Methods: Sixty women who had developed breast cancers before the age of 40, and who were treated at the Soonchunhyang University Hospital, were studied independently of their family histories. The age range was 18 to 40 with a median of 34.5 years. Lymphocyte specimens from peripheral blood were studied for the heterozygous mutations of BRCA1 and BRCA2 using direct sequencing methods. Immunohistochemistry was peformed on the paraffin-embedded tissue blocks that were available. Results: Eleven deleterious mutations (18.3%, 6 in BRCA1 and 5 in BRCA2) and 7 missense mutations of unknown significance (11.7%), were found among the 60 patients. More than half of the mutation were novel, and were not reported in the database. Most of the BRCA-associated patients had no history of breast cancer. No treatment related failures were observed in the BRCA carriers, with the exception of one patient that had experienced a new primary tumor of the contralateral breast. The seven year relapse free survival rate were 50 and 79% In the BRCA carrier and BRCA negative patients, respectively. Although the expression of estrogen and progesterone receptors were less common, and histological features more aggressive, in the BRCA associated tumors, the outcome of the patients with BRCA mutations was not poorer than that on the patients without deleterious mutations. Conclusion.: Despite the BRCA mutation carriers having adverse prognostic features, the recurrence rate was relatively lower than that in the BRCA non-carrying Korean patients wi4h early-onset breast carcinomas. In addition, although the prevalence of the BRCA mutation in Korean patients was higher than that in white patients, the penetrance of the cancer seemed to be relatively low in Korean women carrying BRCA mutations. A large population based study of the BRCA mutation, with a long-term follow-up of the study patients will be required to confirm these results.

Clinical Features and Prognostic Factors in 41 Patients of Primary Nasal/Nasopharyngeal Non-Hodgkin's Lymphoma: Prognostic Significance of Immunophenotype (비/비인강 비호즈킨 림프종의 임상양상과 예후 인자 : 면역 표현형의 임상적 의의)

  • Park Soon-Seo;Park Jong-Beom;Suh Cheol-Won;Park Ji-Woon;Lim Soo-Duk;Huh Joo-Ryung;Nam Soon-Yuhl;Kim Sang-Yoon;Lee Ho-Gyu;Chang Hye-Sook;Kim Tae-Won;Lee Je-Hwan;Kim Sung-Bae
    • Korean Journal of Head & Neck Oncology
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    • v.15 no.2
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    • pp.149-155
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    • 1999
  • Objectives: To study the clinical features of the primary nasal/nasopharyngeal non-Hodgkin's lymphomas and to evaluate the implication of immunophenotyping as a prognostic factor. Patients and Methods: From January 1990 to December 1997,41 patients(median age, 41 years) of primary nasal/nasopharyngeal non-Hodgkin's lymphoma were studied. The clinical records and paraffin-embedded tissue blocks were reviewed retrospectively. The histologic features, immunophenotypic findings(pan-T, pan-B, CD3, CD56) and Epstein-Barr virus in situ hybridizatios were examined. The prognostic factors for clinical outcome were evaluated in these patients. According to Ann-Arbor system, there were 30 patiets(73%) with stage IE, 4(10%) with stage IIE, 3(7%) with stage IIIE, 4(10%) with stage IVE lymphoma. Among the patients with stage IE/IIE, 4 patients received local radiation alone, 4 received chemotherapy alone, 25 received combination chemotherapy and radiotherapy and 1 refused treatment. The patients with stage IIIE/IVE were given combination chemotherapy and radiotherapy. Results: Immunophenotyping were performed in 40 patients and staining results were as follows: 3(7%) patients with B cell, 17(42%) with T cell, 18(44%) with NK/T cell(CD56 positive), and two patients with unclassifiable result. Epstein-Barr(EB) virus in situ hybridization were performed in 28 patients and 23(82%) patients had positive EBV-encoded RNAs(EBERs). 21(55%) patients achieved a complete remission. There was no difference in complete remission between radiation alone and combination therapy. With median follow-up of 30 months, 5-years disease free survival of complete responders was 60% and 5-years overall survival rate was 36%. Multivariate analysis showed that better overall survival was related with absence of B symptoms, ECOG performance${\leq}1$ and non-NK cells. Conclusion: Most of all cases were positive for EBER. Since NK/T phenotype carried the worst prognosis, analysis for CD56 expression should be done. Further prospective studies were warranted to evaluate the role of chemotherapy in stage IE/IIE.

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EXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN AND TYPE I COLLAGEN IN THE ELONGATED BONE IN THE MANDIBLE OF ADULT MONGREL DOGS (성견 하악 골체부 신장시 신장부위의 증식세포핵항원과 제 1형 교원질 발현에 관한 연구)

  • Lim, Sun-Mo;Ahn, Byoung-Keun;Park, Young-Ju;Park, Hee-Geon;Park, Jun-Woo;Rhee, Gun-Joo;Lee, Yong-Chan;Cho, Byoung-Ouck
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.5
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    • pp.385-396
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    • 2001
  • The purpose of this experiment was to examine the histological changes and the pattern of expression of proliferating cell nuclear antigen(PCNA) and type I collagen in the elongated bone affected by osteodistraction of the mandibular body in an adult canine model. Seven adult male mongrel dogs weighing over 20kg were used for this experiment. The author excluded 3 animals because they died before the planned time of sacrifice. The custom-made linear extraoral device and 4 bicortical fixation screws 2.3mm in diameter, 50mm in total length, 15mm in screw length were used in each animal. The distal part of the distractor produced a 0.75mm gap between proximal and distal bony segments every $360^{\circ}$ turn of the rotation rod of the device. The mandibular body of the right side from each animal was experimental side and the left side was left intact and served as control. At the experimental side, the mandibular body was osteotomized. After 5-day latency period, the segments were distracted with a rate of 1.1mm/day and a rhythm of two/day for ensuing 7 days. The animals were sacrificed at the 4th. 17th, and 32th day after the end of the distraction. The bony specimens were decalcified, embedded in paraffin, sectioned $5{\mu}m$ thick and stained with Masson trichrome and examined under the light microscope. The immunohistochemical examinations using anti-PCNA antibody and anti-type-I collagen antibody were performed to examine the pattern of the expression of PCNA and type I collagen, respectively. Results : 1. The mean increment of the distance between the proximal and distal screw-holding parts of the distractor was 6.8mm. The average elongation of the mandible in the experimental side was 5.3mm. The loss of elongation was 1.5mm in average. 2. New bone was already observed at the 4th. day after the end of distraction. But, bony union was not completed in the distraction gap at the 32th. day after the end of distraction by radiographic and microscopic examinations. 3. The expression rate of PCNA positive cells in the distraction gap had a tendency of decrease from 35.1-68.8% initially, to 49.1%, and finally to 17.6-27.2%. But at the final period, the tissue of the elongated gap still had the ability of cell proliferation. On the other hand, the expression of PCNA positive cells in the control side were negligible through the experimental period. 4. PCNA positive cells were observed primarily both at the central fibrous zone and at the region of just adjacent to CFZ which initiated new bone formation. 5. The expression pattern of the type I collagen was not zone-specific. They were observed diffusely throughout the elongation gap. 6. The predominant mechanism of new bone formation in the distraction gap was intramembranous. But, some of the regenerated bone was formed by endochondral ossification.

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Expression of p53 in Human Primary Lung Cancers (인체 폐암종에서 p53의 발현에 관한 연구)

  • Lee, Young-Kyu;Park, Sung-Soo;Shin, Dong-Ho;Lee, Dong-Hoo;Lee, Jung-Hee;Lee, Jung-Dal
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.4
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    • pp.395-403
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    • 1993
  • Background: The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Alteration or inactivation of p53 by mutations, or by its interactions with oncogene products of DNA tumor viruses, can lead to cancer. Mutations of the p53 gene occur frequently in human primary lung cancers and the wild-type p 53 allele is often concomitantly deleted. These suggest that deprivation of suppressive role of the wild-type p53 may ensure tumor cell growth presumable by the mutant p53 gene. Methods: In an attempt to investigate this hypothesis, a mutant p53 gene was immunohistochemically demonstrated in the formalin-fixed paraffin-embedded tissue sections of lung cancers by using a monoclonal antibody p53 (Ab-3 and clone DO7). Results: The expression of p53 (DO7) was found in all four normal lung tissues, four small cell carcinomas, and four non small cell carcinomas in histologic types of lung cancer. In the six normal lung tissues the expressions of p53 (Ab-3) were not found. Contrarily, the expression of p53 (Ab-3) was found in the nuclei of lung cancers among fifteen (46.9%) of thirty-two cases studied. The expression of p53 (Ab-3) was disclosed in three case (37.5%) of eight small cell carcinomas and twelve cases (50.0%) of twenty-four non small cell carcinomas in histologic types of lung cancer. Conclusion: These findings suggest that expression of the mutant p53 is related to the one of events in the pathogenesis of human lung cancer and the role of the other oncogenes might be also related to the development of lung cancers.

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Expression of Transforming Growth Factor-Beta in Patients with Interstitial Lung Diseases (ILD) (간질성 폐질환환자에서 Transforming growth factor-beta의 발현에 관한 연구)

  • Park, Sung-Soo;Lee, Kyung-Sang;Yang, Suck-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Lee, Dong-Hoo;Lee, Jung-Dal;Lee, Jung-Hee
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.164-172
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    • 1996
  • Background : Transforming growth factor-$\beta$(TGF-$\beta$) may play a role in a variety of fibroproliferative disorders including pulmonary fibrosis via the induction of extracellular matrix accumulation. TGF-$\beta$ not only stimulates extracellular matrix production, but also decreases matrix degradation. Interstial lung diseases have demonstrated marked expression of TGF-$\beta$. Methods : To evaluate the possible role of TGF-$\beta$ in human pulmonary fibrosis, by using neutralizing antibody of TGF-$\beta$ we investigated immunohistochemically the expression of TGF-$\beta$ in the formalin-fixed, paraffin-embedded tissue sections of the 5 normal cases for the control, and a couple of pieces of tissues taken out of 3 cases with idiopathic pulmonary fibrosis, 3 cases with ILD from bleomycin toxicity, 3 cases with ILD from sarcoidosis, and 3 cases with ILD from eosinophilic granuloma. Results : In the 5 normal cases for the control, the TGF-$\beta$ was expressed in bronchial and alveolar epithelial cells. Up-regulation of the TGF-$\beta$ expression was showed in the interstitial fibroblast cells of alveolar septa in 5 pieces and proliferated alveolar pneumocytes in 1 piece among 6 pieces tissues taken out of 3 cases with idiopathic pulmonary fibrosis. Also up-regulation of the TGF-$\beta$ expression was showed in alveolar lining pneumocytes, intra-alveolar mononuclear cells, and epithelioid cells in most of cases of ILD from bleomycin toxicity, sarcoidosis and eosinophilic granuloma. Conclusion : These findings suggest that up-regulation of the TGF-$\beta$are involved in pathogenesis of interstitial lung fibrosis from variety of causes.

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Electron Microscopic Studies on Olfactory Bulbs in the Vertebrates by Phylogenetics (계통발생에 따른 척추동물의 뇌후구에 대한 전자현미경적 연구)

  • Choi, W.B.;Chung, Y.H.;Seo, J.E.
    • Applied Microscopy
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    • v.15 no.2
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    • pp.31-68
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    • 1985
  • Authors are trying to unveil the ultrastructural organization of olfactory bulb, which has been summerized under light microscopic level or communicated only in some detail in different view point until now. For the critical point of view, since the phylogenetical approach will give the ultimate value in the correlative study between structural and functional bases (Brodal, 1969), the present study was carried out light and electron microscopic analyses of the structures of the neurons and synaptic organizations in olfactory bulbs from different animals in phylogenetical scale. We selected each one species from five animal classes: the house rabbit(Oryctolagus cuniculus var. domesticus [Gmelin]) from Mammalia, the domestic fowl (Gallus gallus domesticus Brisson) from Aves, the viper (Agkistrodon hylys [G.P. Pallas]) from Reptilia, a frog (Bombiana orientalis Boulenger) from Amphibia and the crussian carp (Carassius carassius [Linne]) from Pisces. For light microscopic study, samples were fixed in 10% formalin and paraffin sections were stained with hematoxylin-eosin. For the electron microscopic study, the tissues were fixed by perfusion through the heart or immersion with 1% paraform-aldehyde-glutaraldehyde mixture (phosphate buffer, pH 7.4), and final tissue block trimmed under dissecting microscope were osmicated (1% OsO4), they were embedded in Araldite or Epon 812, and ultrathin sections were made by LKB-V ultratome following the inspection of semi-thin sections stained with toluidine blue-borax solution. Ultra-thin sections contrasted with uranyl acetate and lead citrate were observed with JEM 100CX electron microscope. We have summerized our morphological analyses as follows: 1. The olfactory bulb of rabbit, viper and frog shows the eight layers of fila olfactoria, glomerular, external granular, external plexiform, mitral cell, internal plexiform, internal granular, medullary but domestic fowl shows the five layers of glomerular, fibrillar, mitral, granular and medullary and the three layers of fibrilla, glomerular and medullary in crussian carp. The sharpness of demarcation between the layers shows deferential tendency according to phylogenetical order. 2. Mitral cells of vertebrate have large triangular or oval shape with spherical nuclei which contain not so much chromatin. The cytoplasm contains numerous cell organelles, of which Nissl's bodies or granular endoplasmic reticula arranged as parallel strands. Development of granular endoplasmic reticula were declined as the phylogentical grade is going lower. 3. Tufted cells of all animal are mostly spindle or polygonal contour and contain oval nuclei which located in periphery of cytoplasm. The nuclei of rabbit, fowl, viper and frog has relatively space chromatin, but a nucleus of crussian carp contain irregularly aggregated chromatin in karyoplasm. Their cytoplasmic volume and cell organelle contents are in between those of mitral cell and granular cell. They contain moderate amount of mitochondria, granular endoplasmic reticula, a few Golgi complex, polysomes, lysosome, etc. 4. Granule of cells of all the vertebrate amimals studied exhibit similar features; cells and their dense nuclei show spherical or oval contour, and they have the thin rim of cytoplasm which contain only a few cell organelles. 5. In rabbit, the soma of mitral cells were in contact with boutons with two types of synaptic vesicles, that is, round and flat vesicles, especially flat vesicles in boutons were showing reciprocal synapses. However, in domestic fowls, vipers, frogs and crussian carps, there were found boutons showing only spherical synaptic vesicles. 6. The boutons containing round synaptic vesicles were made contact with the some of tufted cell of olfactory bulb in the rabbits, fowls, vipers and frogs, but no synaptic boutons were observed in soma of tufted cells in crussian carps. In the frogs, there were observed dendrites were contact with the soma of tufted cells. 7. In the neuropils of plexiform, granular and glomerular layers olfactory bulbs in the vertebrate, the synapses were axo-large dendrites, axo-median and small dendrites, dendrodendritic, and axo-axonal contacts. However, in the neuropil of crussian carps, synapses were observed only in glomerular layer.

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A Study of Microsatellite Instability in Primary Small Cell Lung Cancers by Microsatellite Analysis (원발성 소세포폐암에서 Microsatellite 분석을 이용한 Microsatellite 불안정화에 대한 연구)

  • Cho, Eun-Song;Chang, Joon;Park, Jae-Min;Shin, Dong-Hwan;Kim, Se-Hoon;Kim, Young-Sam;Chang, Yoon-Soo;Cho, Chul-Ho;Kwak, Seung-Min;Lee, Jun-Gu;Chung, Kyung-Young;Kim, Sung-Kyu;Lee, Won-Young;Kim, Se-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.2
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    • pp.180-190
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    • 2000
  • Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

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The Relationship between Expression of EGFR, MMP-9, and C-erbB-2 and Survival Time in Resected Non-Small Cell Lung Cancer (수술을 시행한 비소세포 폐암 환자에서 EGFR, MMP-9 및 C-erbB-2의 발현과 환자 생존율과의 관계)

  • Lee, Seung Heon;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Ha, Eun Sil;Kim, Jeong-Ha;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sung Yong;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa;Kim, Chul Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.3
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    • pp.286-297
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    • 2005
  • Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.