Loss of Tumor Suppressor ARID1A Protein Expression Correlates with Poor Prognosis in Patients with Primary Breast Cancer

조현득,이종은,정해연,오미혜,이지혜,장시형,김경주,한선욱,김성용,김한조,배상병,이현주 한국유방암학회 2015 Journal of breast cancer Vol.18 No.4

Purpose: Somatic mutations of the chromatin remodeling AT-rich interactive domain 1A (SWI-like) gene (ARID1A) have been identified in many human cancers, including breast cancer. The purpose of this study was to evaluate the nuclear expression of ARID1A in breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance. Methods: IHC was performed on tissue microarrays of 476 cases of breast cancer. Associations between ARID1A expression and clinicopathologic characteristics and molecular subtype were retrospectively analyzed. Results: Low expression of ARID1A was found in 339 of 476 (71.2%) cases. Low expression of ARID1A significantly correlated with positive lymph node metastasis (p=0.027), advanced pathologic stage (p=0.001), low Ki-67 labeling index (p=0.003), and negative p53 expression (p=0.017). The ARID1A low expression group had significantly shorter disease-free and overall survival than the ARID1A high expression group (p<0.001 and p<0.001, respectively). Multivariate analysis demonstrated that low expression of ARID1A was a significant independent predictive factor for poor disease-free and overall survival in patients with breast cancer (disease-free survival: hazard ratio, 0.38, 95% confidence interval [CI], 0.20–0.73, p=0.004; overall survival: hazard ratio, 0.11, 95% CI, 0.03–0.46, p=0.003). In patients with luminal A type disease, patients with low ARID1A expression had significantly shorter disease-free and overall survival rates than patients with high ARID1A expression (p=0.022 and p=0.018, respectively). Conclusion: Low expression of ARID1A is an independent prognostic factor for disease-free and overall survival in breast cancer patients and may be associated with luminal A type disease. Although the biologic function of ARID1A in breast cancer remains unknown, low expression of ARID1A can provide valuable prognostic information.

유방암에서 안드로겐 수용체, bcl-2 단백, Rb 단백의 발현과 예후인자와의 상관관계에 관한 연구

조현득,김영식,김인선 대한병리학회 1998 Journal of Pathology and Translational Medicine Vol.32 No.6

Inactivation Pattern of p16 Gene in Non-Hodgkin’s Lymphomas

조현득,김인선 대한병리학회 2002 Journal of Pathology and Translational Medicine Vol.36 No.6

Background : Loss of heterozygosity (LOH) and mutation of the p16 tumor suppressor gene have been detected in non-Hodgkin’s lymphomas (NHLs). Recently, hypermethylation of the p16 gene has been reported. The role of p16 gene alterations in the genesis of NHLs and their high-grade transformations require explanation. Methods : LOH of D9S171 and IFNA microsatellite markers, DNA hypermethylation, and mutation of exon 1 and 2A were assessed in 43 cases of NHLs. The genetic abnormalities were compared with the protein expression by immunohistochemistry, and they were evaluated according to the histologic subtypes, grades and immunophenotypes. Results : DNA hypermethylation was the most common p16 gene abnormality and was found in 30 of 39 cases (76.9%). Eight cases (18.6%) showed LOH in one or both microsatellite markers, and five cases (11.6%) showed mutations in exon 1 or 2A. Loss of protein expression was seen in 17 cases (39.5%) and was associated with mutation and LOH. Loss of protein was more frequent in high-grade lymphomas than in low-grade lymphomas. Conclusion : These results suggest that the functional loss of the p16 gene contributes to the development of NHLs, especially to the development of high-grade lymphomas.

위 선암종에서 p63의 발현 양상

조현득,양승하 순천향대학교 순천향의학연구소 2008 Journal of Soonchunhyang Medical Science Vol.14 No.1

The recent discovery of p63, a homologue of p53, has been expected to expand our understanding of p53. It has been known that p63 is almost exclusively expressed in normal squamous epithelia and overexpressed in squamous cell carcinomas, but not in adenocarciomas. The aim of this study was to evaluate the p63 status of gastric adenocarcinoma. The status of p63 was evaluated by immunohistochemical stain in seventy-seven cases of gastric adenocarcinoma. We found that p63 was expressed in only a few normal gastric epithelia but expressed in fifty-four tumors (70.1%). p63 was overexpressed in advanced gastric carcinomas and poorly differentiated carcinomas of women. These results indicated that p63 was associated with invasivenes and aggressiveness of gastric adenocarcinoma. In conclusion, in this study p63 was overexpressed in gastric adenocarcinomas and contributed for growing tumors.

조기위암에서 침윤, 유형 및 분화도에 따른 p53, bcl-2의 발현

권오선,조현득,오미혜,김의한,양승하 순천향의학연구소 2006 Journal of Soonchunhyang Medical Science Vol.12 No.2

Purpose: For evaluation of the role of tumohgenesis of p53 over expression and bcl-2 inhibition in early gastric cancer, the immunohistochemical tissue status of 31 primary early gastric cancer patients was investigated, and also the association between p53 , bcl-2 expression status and clinicopathologic parameters was analyzed for evaluation of prognostic relevance. Materials and Methods: DO7, a monoclonal antiserum to p53 protein and clone 124, monoclonal antibody to bcl-2 protein were used for the immunohistochemical analysis in 31 primary early gastric cancer tissue. The expressions were scored and divided into negative, positive, low expression, and over expression. Results: The clinocopathologic parameters; tumor depth of invasion, histologic type and differentiation were not related with the expression status of p53 and bcl-2. In 31 cases, the p53 over expression was 14 cases(45.2%), and the bcl-2 positive expression was 15 cases(48.4%), and 9 cases(29.0%) were the status of p53 over expression and bc1-2 positive expression. Conclusions: These results suggest that altered cell cycle and apoptosis control by p53 and bcl-2 may be an event in carcinogenesis of early gastric cancer but there are many other mediators that may fascilitate tumorigenesis.

대장암에서의 Hypoxia Inducible Factor-1α (HIF-1α) 및 Vascular Endothelial Growth Factor (VEGF): 예후 및 종양표지자로서의 가능성

최윤영,조현득,박동국,김성용,이문수,김창호,조무식,백무준 대한대장항문학회 2008 Annals of Coloproctolgy Vol.24 No.5

Purpose: Angiogenesis is one of the key steps in solid tumor growth and metastasis. We investigated the prognostic significance of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) expressions as markers of angiogenesis in colon cancer. Methods: We retrospectively reviewed the medical records of 78 patients with colon or rectal cancer who underwent a surgical resection at Soonchunhyang University Hospital from January 2000 to December 2001, and we evaluated the expression of VEGF and HIF-1α in archival tumor tissues by using immunohistochemistry. We recorded the clinical and the pathological characteristics of the patients and analyzed their survival outcomes. Results: Thirty-four (34) patients were male, and the mean age of all the patients was 66.7 years. HIF-1α and VEGF were positive in 56% (44 patients) and 53% (42 patients) of the tumors, respectively. HIF-1α expression was significantly associated with several pathological parameters, such as TNM stage (P=0.001), lymph node metastasis (P=0.001). HIF-1α expression was also associated with VEGF expression (P=0.032). The survival of patients with HIF-1α expression was worse than that of patients with no HIF-1α expression (P=0.036). However, VEGF expression was not associated with other pathological characteristics. Conclusions: We suggest that, in cases of colorectal cancer, HIF-1α expression may be associated with expression of VEGF, progression of tumors, and poor prognosis.

Loss of FAT Atypical Cadherin 4 Expression Is Associated with High Pathologic T Stage in Radically Resected Gastric Cancer

정해연,조현득,오미혜,이지혜,이현주,장시형,이문수 대한위암학회 2015 Journal of gastric cancer Vol.15 No.1

Variable cytoplasmic expressions of FAT4 were observed in gastric cancers, with 33 cases (24.3%) showing loss of expression (H-score <10). Loss of FAT4 expression was associated with an increased rate of perineural invasion (H-score <10 vs. ≥10, 36.4% vs. 16.5%, P=0.015), high pathologic T stage (P=0.015), high tumor-node-metastasis stage (P=0.017), and reduced disease-free survival time (H-score <10 vs. ≥10, mean survival 62.7±7.3 months vs. 79.1±3.1 months, P=0.025). However, no association was found between the loss of FAT4 expression and tumor size, gross type, histologic subtype, Lauren classification, lymphovascular invasion, or overall survival.

Calcifying Aponeurotic Fibroma of the Elbow - A Case Report -

오미혜,조현득,박용구,정은아,이지혜,한종규 대한병리학회 2009 Journal of Pathology and Translational Medicine Vol.43 No.1

Calcifying aponeurotic fibroma is a rare soft tissue tumor that mostly occurs in the distal extremities of children and adolescents. We report here on a case of calcifying aponeurotic fibroma of the right elbow in an 8-year-old boy, and the tumor was diagnosed by surgical excision. The patient complained of painless swelling and mild limitation of the range of motion of the elbow joint. Radiologically, the mass was ill-defined and showed stippled calcification with shallow bony erosion. Microscopically, the tumor was composed of spindle cells with nodular deposits of hyalination and calcification, and these deposits were surrounded by palisading polygonal plump cells. Immunohistochemically, the tumor showed a diffuse positive expression for CD99 and negativity for smooth muscle actin, S-100 protein and CD34. The patient has been well with no signs of recurrence during the 42 months after surgery. Calcifying aponeurotic fibroma is a rare soft tissue tumor that mostly occurs in the distal extremities of children and adolescents. We report here on a case of calcifying aponeurotic fibroma of the right elbow in an 8-year-old boy, and the tumor was diagnosed by surgical excision. The patient complained of painless swelling and mild limitation of the range of motion of the elbow joint. Radiologically, the mass was ill-defined and showed stippled calcification with shallow bony erosion. Microscopically, the tumor was composed of spindle cells with nodular deposits of hyalination and calcification, and these deposits were surrounded by palisading polygonal plump cells. Immunohistochemically, the tumor showed a diffuse positive expression for CD99 and negativity for smooth muscle actin, S-100 protein and CD34. The patient has been well with no signs of recurrence during the 42 months after surgery.

전립선암 진단에서 P504S와 34βE12 면역염색의 유용성

윤종현,조현득,김두상,이창호 대한비뇨의학회 2007 Investigative and Clinical Urology Vol.48 No.7

Efficacy of three fine needle biopsy techniques for suspected pancreatic malignancies

이가영,조현득,황보영,양재국,한수정,최현종,이윤나,차상우,문종호,조영덕,박상흠,이태훈 대한내과학회 2018 대한내과학회 추계학술대회 Vol.2018 No.1