• Korean Journal of Head & Neck Oncology
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• v.27 no.1
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• pp.32-37
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• 2011

서 론 : 미세갑상선유두상암종 환자에서 불필요한 예방적 중앙 림프절절제술을 피하기 위해서 림프절 전이를 수술 전에 예측하는 수단이 필요하다. 림프관 생성 및 성장의 조절에 VEGF-C/D, VEGFR-3 pathway, podoplain이 관여된다는 사실이 밝혀져 있다. 림프관 생성 및 성장과 관련된 인자인 VEGF-C/D, podoplanin에 대한 면역조직화학염색과 반정량적 분석을 통해 미세갑상선유두상암종에서 림프절전이와의 관련성을 확인하고자 하였다. 대상 및 방법 : 2006년 9월부터 2008년 6월까지 본원에서 미세갑상선유두상암종으로 진단받고 1인 술자에 의해 갑상선 전 절제술 및 예방적 중앙 림프절절제술을 받은 104명의 환자 중 중앙 림프절 전이가 있었던 환자와 없었던 환자를 각각 25명씩 무작위로 선별하여 종양부위에 면역화학염색을 실시하여 림프관생성인자의 발현 정도를 비교하였다. 결 과 : 대상군 50예 중 VEGF-C/D는 50예(100%) 모두 발현이 되었고 podoplanin은 33예(66%)에서 발현이 되었다. 그 중 VEGF-C는 10예(20%)에서 약한 양성, 37예(74%)에서 중등도 양성, 3예(6%)에서 강한 양성소견을 보였고 VEGF-D는 9예(18%)에서 약한 양성, 37예(74%)에서 중등도 양성, 4예(8%)에서 강한 양성소견을 보였다. 중앙 림프절 전이 음성 환자 군과 양성 환자 군으로 분류하였을 때 VEGF-C/D의 발현율의 차이는 p-value가 각각 0.48, 1.00으로 통계적으로 유의한 차이를 보이지 않았다. 50예 전체를 대상으로 하여 종양의 개수, 최대크기, 검출된 전체 림프절의 수, 양성 림프절의 수, 주변조직 침범여부에 따른 VEGF-C/D의 발현도 통계적으로 유의한 차이를 보이지 않았다. Podoplanin의 경우 염색 여부에 따라 양성군과 음성군으로 나누어 분석하였을 때 종양의 개수, 최대크기, 검출된 림프절의 수, 양성 림프절의 수, 주변조직 침범여부도 통계적으로 유의한 차이를 보이지 않았다. 결 론 : VEGF-C/D는 대상군 전체(100%)에서 발현이 되었고 podoplanin은 66%에서 발현이 되었다. 림프관 생성인자로 알려진 VEGF-C/D및 podoplanin이 미세갑상선유두상암종에서 많이 발현이 되는 것으로 보아 위 인자들이 림프절 전이를 일으키는 인자 중 하나로 생각된다. 하지만 미세갑상선유두상암종에서 중앙 림프절 전이를 예측할 수 있는 인자로 부적합 한 것으로 생각되며 향후 더 많은 증례를 통해 관련성 여부에 대한 연구가 필요하고 또 다른 인자의 관련성에 대해서 연구가 필요하겠다.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.56-64
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• 2008

Purpose: Cathepsin D(CD) is a lysosomal acid proteinase that is related to malignant progression, invasion, and a poor prognosis in several tumors. The aim of this study was to evaluate the prognostic clinical significance of CD and p53 expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer who were treated with preoperative chemoradiation. Materials and Methods: Eighty-nine patients with locally advanced rectal cancer(cT3/T4 or N+) were included in this study. Preoperative chemoradiation consisted of a dose of 50.4 Gy of pelvic radiation and two concurrent cycles of administration of 5-fluorouracil and leucovorin. Surgery was performed six weeks after chemoradiation. CD and p53 expression in pretreatment formalin-fixed paraffin-embedded tumor biopsy specimens were assessed by immunohistochemical staining using a CD and p53 monoclonal antibodies. The threshold value for a positive stain in tumor tissue and stromal cells was 1+ intensity in 10% of the tumors or stromal cells, respectively. Results: Positive CD expression was found in 57(64%) of the tumors and 32(35%) of the stromal cell specimens. There was no association with CD expression of the tumor or stromal cells and patient characteristics. There was a correlation between tumor CD expression with stromal cell CD expression(p=0.01). Overexpression of p53 was not a significant prognostic factor. The 5-year overall survival(OS) and disease-free survival(DFS) rates were not different between tumor CD-negative and positive patient biopsy samples(69% vs. 65%, 60% vs. 61%, respectively). The 5-year OS rates in the tumor-negative/stromal cell-negative, tumor-negative/stromal cell-positive, tumor-positive/stromal cell-negative and tumor-positive/stromal cell-positive biopsy samples were 75%, 28%, 62%, and 73%, respectively. Stromal cell staining only without positive tumor staining demonstrated the worst overall survival prognosis for patients(p=0.013). Conclusion: Overexpression of p53 in rectal biopy tissue was not associated with prognostic significance. In the pretreatment biopsy specimens, an exclusive increase in CD expression in stromal cells without tumor expression was related to poor overall survival in patients with locally advanced rectal cancer treated with preoperative chemoradiation.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.6
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• pp.499-510
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• 2006

Malignant tumors of the human salivary glands may arise from major or minor salivary glands. Adenoid cystic carcinoma (ACC) is the second most common malignant neoplasm in the salivary glands. ACC is occasionally highly aggressive tumor that readily invades adjacent tissues and metastasize to distant organs at early stages of the disease. Although ACC tends to grow slowly, treatment outcome may be poor due to wide local infiltration, perineural or intraneural spread and a propensity for hematogenous metastasis. Therefore, knowledge of cellular and molecular characteristics that influence the growth, survival and metastasis of tumor cells, is important for new treatment strategies of salivary ACC. I determined expressions of epiderma growth factor (EGF)-signaling molecules using surgical specimens of human ACCs. Protein expressions of EGF, transforming growth $factor(TGF)-{\alpha}$, EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and human EGF receptor (HER)-2 were assessed in 18 cases of salivary ACC by immunohistochemical staining. Adjacent normal salivary tissues and mucosal tissues, uninvolved by the malignant tumor, served as internal controls. Most of the tumors, especially ACC with a tubulocribriform pattern, were positive for EGF signaling molecules. The overall percentages of the 18 specimens expressing EGF, $TGF-{\alpha}$, EGFR, pEGFR, and HER2 were 50, 89, 61, 61 and 83% respectively. Moreover, tumor-associated endothelial cells and infiltrating immune-related cells in the stroma of ACC, also expressed these biomarkers. Taken together, EGF-signaling molecules are actively expressed in salivary ACC. Therefore, we suggest that these biomarkers can be molecular targets for new treatment strategies of salivary tumors.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.973-981
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• 1998

Background: About 30% to 40% of the patients with pathologic stage I non-small cell lung cancer (NSCLC) die within 5 years after complete resection. The identification of poor prognostic factors and the application of additional treatment are very important to improve the survival rate in resected stage I NSCLC. Materials and methods: Sixty-eight(68) patients who had been diagnosed postoperatively between Janury 1989 and December 1995 as having stage I non-small cell lung cancer according to the TNM classification were studied. The postoperative 5-year survival rate was calculated with the Kaplan-Meier method, and clinico- histopathologic factors including age, sex, operative method, type of tumor cell, T factor, grade of the differentiation in a squamous cell carcinoma, invasion of blood vessel and expression of the nm23-H1 protein were investigated and analyzed. Results: The median survival of the entire group of patients was 58$\pm$3 months, with a 5-year survival of 58.9%. In univariate analysis, invasion of blood vessel and poor differentiation of the tumor cell in a squamous cell carcinoma significantly worsened the survival. In multivariate analysis, invasion of blood vessel and grade of the differentiation of the tumor cells in a squamous cell carcinoma remained independent prognostic factors. High expression of the nm23-H1 protein was related to a high postoperative 5-year survival in comparision with low expression of the nm23-H1 pretein (73.0% vs 50.7%), but there was no statistical significance. Conclusions: These results highlight the negative prognostic value of poor differentiation of tumor cells in a squamous cell carcinoma and invasion of blood vessel in stage I non-small cell lung cancer. Also, further studies are necessary to be determined prognostic value of the T factor and expression of the nm23 protein in non-small cell lung cancer.

• Korean Journal of Head & Neck Oncology
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• v.29 no.1
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• pp.1-10
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• 2013

연구배경 및 목적 표피성장인자수용체(EGFR)는 HER2/neu(erbB2), HER3(erbB3), HER4(erbB4)를 포함하는 receptor tyrosine ki-nase의 erbB 그룹에 속하는 수용체이다. 표피성장인자수용체의 과발현은 다양한 종류의 암, 특히 두경부편평세포암에서 예후를 악화시킨다고 알려져 있다. 이에 저자들은 하인두편평세포암에서 표피성장인자수용체의 발현 및 분포를 확인하고, 하인두암에서 표피성장인자(EGF)가 암세포의 증식과 침습에 미치는 영향에 대해 알아보고자 하였다. 대상 및 방법 57명의 하인두편평세포암 환자의 조직에서 표피성장인자수용체의 발현을 면역화학적염색을 통해 확인하고, 이에 대해 임상병리학적 요인과 생존율에 대한 분석을 시행하고, 일부 환자의 정상 및 암조직에서 Western blot을 시행하였다. 하인두편평세포암 세포주인 FaDu에서 proliferative assay, colony dispersion, wound healing assay, invasion assay를 시행하여, 하인두암의 진행에서 표피성장인자의 역할에 대하여 분석하였다. 또한 RT-PCR과 Zymography를 통하여 Matrix metalloproteinase(MMP)-2, 9의 발현을 확인하였다. 결 과 63.2%의 하인두편평세포암 조직에서 표피성장인자수용체의 발현이 확인되었다. 표피성장인자수용체의 발현은 정상조직에서 비하여 하인두암 조직에서 유의하게 증가되어 있었으며, 병리학적 병기(p=0.022)가 올라갈수록 유의하게 증가하였으나, 증례수의 제한으로 생존율에서는 통계적 유의성을 얻지는 못했다(p=0.053). in vitro의 결과로 표피성장인자를 FaDu 세포주에 처리하였을 때, FaDu 세포주의 증식이 유의하게 증가되었으며(p<0.05), Transwell invasion chamber상 침습의 증가가 확인되었다(p<0.05). RT-PCR과 zymogram 실험상 표피성장인자처리시 FaDu 세포주의 MMP-2, 9이 발현이 증가되고 활성화되는 것이 확인하였다. 결 론 본 연구에서 표피성장인자수용체의 과발현이 하인두암의 예후 인자로서의 가능성을 확인하였고, 표피성장인자가 하인두편평세포암의 증식과 침습에 관여하는 것을 확인하였다.

• 대한두경부종양학회:학술대회논문집
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• 1997.11a
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• pp.282.1-282.1
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• 1997

• 대한두경부종양학회:학술대회논문집
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• 1992.11a
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• pp.131.1-131.1
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• 1992

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.298-305
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• 2015

Stem cell-like tumor cells are reported to be the main reason for tumor recurrence and metastasis. As one of the new approaches to overcome cancer, studies are emerging to inhibit the expressions of stem cell transcriptional factors (Oct4, Sox2, Klf-4, and Lin28) in cancer cells. MicroRNAs are master genetic regulators that can control development and differentiation of stem cells. In this study using various ovarian tumors (Skov3, Ovcar3, Tov112D, Tov21G, PA-1 and Hsc832(c)T), we examined the expressions of stem cell-related transcription factors, and the biological changes in cell survival and growth by miR-126 that targets stem cell transcriptional factors. We observed that treatment of miR-126 induced the morphological changes and cell suspension in most cells. In addition, miR-126 induced gradual regression of cell division except Skov3 cells, especially significant time-dependent reduction in Tov112D, Tov21G and PA-1. When we examined the expression of stem cell transcriptional factors, Sox2 was shown to be down-regulated after miR-126. Our results demonstrate that miR-126 treatment can provide the reversible environment to regulate cell division and to induce cell death of ovarian tumors, suggesting the molecular biological clues for clinical usage.

• Investigative Magnetic Resonance Imaging
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• v.1 no.1
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• pp.125-129
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• 1997

Purpose: The aim of this study was to find correlation between the expression of epidermal growth factor receptor (EGFR) and MR findings in the brain glioma. Materials and Methods: MR features including edema, margin, necrosis, heterogeneity, hemorrhage and contrast enhancement were retrospectively analyzed with preoperative MR images in 41 patients with proven brain gliomas (8 low grade astrocytomas, 12 anaplastic astrocytomas, 21 glioblastoma multiformes). Immunohistochemical study of EGFR was done and their expressions were graded by both stained distribution and intensity. Correlation analysis between the MR features and EGFR expressions was done. Results: Peritumoral edema was correlated with both distribution (r=0.71, p=0.00) and stain intensity (r=0.69, p=0.00) of EGFR expression. Other MR features showed no statistical correlation with EGFR expression. Conclusion: MRI is useful in evaluation of brain glioma, and peritumoral edema is useful finding that suggests EGFR expression as well as malignant histopathologic grade of the tumor.

• The Journal of the Korean bone and joint tumor society
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• v.9 no.1
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• pp.77-83
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• 2003

Aggressive fibromatosis is a rare soft tissue tumor with locally invasive and infiltrative characteristics. The mechanism of this invasive nature was not reported until now. Mutations or reduction of PTEN, tumor suppressor gene, in cancer tissues, have been found to be associated with invasiveness and metastatic properties of cancer cells. To know the pattern of expression of PTEN in aggressive fibromatosis, we analysed the expression of PTEN with immunohistochemical stain and immunoblotting. PTEN was homogeneously expressed in the normal musculoaponeurotic tissues, but absent or very faint in tissues of patients with aggressive fibromatosis as evidenced by western blot analysis and immunohistochemical examinations. Although the meaning of decreased PTEN expression in aggressive fibromatosis is not certain, it might be involved in the growth of the aggressive fibromatosis, and associated with phenotype of aggressive fibromatosis.