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.

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

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.

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.

Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer

배상병,조현득,오미혜,이지혜,장시형,홍순억,조준훈,김성용,한선욱,이종은,김한조,이현주 한국유방암학회 2016 Journal of breast cancer Vol.19 No.3

Purpose: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. Methods: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas. Results: High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (p<0.001), negative lymph nodes (p=0.011), early pathologic stage (p=0.025), high tumor-infiltrating lymphocyte (TIL) (p<0.001) counts, negative estrogen receptor (p<0.001) and progesterone receptor (p=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (p=0.003), cytokeratin 5/6 (p=0.011), epidermal growth factor receptor (p<0.001), and p53 (p<0.001) expression, and high Ki-67 proliferating index (p<0.001). Based on intrinsic subtypes, high PD-L1 expression and high TIL counts were significantly associated with the HER2 and triple-negative basal type (p<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (p=0.041) and overall survival (OS) (p=0.026) in the univariate analysis, but not in the multivariate analysis. Higher TIL levels was an independent prognostic factor for decreased disease progression (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.284–4.445; p=0.006) and overall death (HR, 3.666; 95% CI, 1.561–8.607; p=0.003). Conclusion: PD-L1 protein expression in breast cancer is associated with better DFS and OS, but is not an independent prognostic factor. High PD-L1 expression was significantly associated with high TIL levels. This finding has important implications for antibody therapies targeting the PD-1/PD-L1 signaling mechanism in breast cancer.

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

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

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Diagnosis of Intestinal Tuberculosis by Polymerase Chain Reaction

Oh, Hwa Eun,Cho, Hyun Deuk,Choi, Jong Sang 고려대학교 의과대학 1998 고려대 의대 잡지 Vol.35 No.3

장결핵이 의심되는 42예의 생검 혹은 절제된 조직에서 PCR과 AFB 염색, 그리고 Rhodamine-Auramine 형광 염색(RAF-AFB)을 시행했다 환자는 만성 설사와 복통을 호소하였고 복통이 가장 흔한 증상이었다(76%). 병리학적 소견상, 10예에서 만성 건락성 육아종성염증으로 진단되었고. 32예는 만성 비건락성 육아종성 염증으로 진단되었다. Ziehl-Neelsen(ZN) AFB 염색에서 25예 중 11예에서 결핵균이 관찰되었으며(44%) Rhodamine-Auramine 형광 염색에서는 25예 중 13예에서 결핵균이 관찰되었다(52%). 25예 중 9예에서 Ziehl-Neelsen(ZN) AFB염색과 RAF-AFB 염색 모두에서 결핵균이 관찰되었으며. 6예는 두 AFB 염색중 어느 하나에서 결핵균을 관찰할 수 있었으므로 15예에서 결핵균을 관찰할 수 있었다(60%). PCR에서 전체 42예 중 8예에서 결핵균의 DNA를 확인할 수 있었다(19%). 비록 PCR이 장결핵의 진단에 있어서 빠르고, 민감한 방법이기는 하나, 우리의 실험결과에 의하면 상대적으로 덜 민감한 방법이었다. 그러므로, 결핵균을 검출하는데 있어서 AFB 염색과 PCR을 병행하는 것이 진단의 정확도를 높일 수 있으리라 생각한다. With 42 endoscopically biopsied or resected tissues, we performed a polymerase chain reaction(PCR), acid fast bacilli(AFB) stain assay and Rhodamine-Auramine fluorescent acid-fast (RAF-AFB) staining. With clinical impressions of intestinal tuberculosis, specimens were obtained from patients with chronic diarrhea or abdominal pain. Abdominal pain was the most common symptom (76%). On pathologic findings, ten of forty-two cases were diagnosed as chronic caseating granulomatous inflammation and thirty-two cases were diagnosed as chronic noncaseating granulomatous inflammation. Ziehl-Neelsen(ZN) stain from formalin-fixed, paraffin-embedded tissue revealed AFB in eleven of twenty-five cases(44%). Rhodamine-Auramine fluorescent acid-fast staining revealed AFB in thirteen of 25 cases(52%). Nine of 25 cases showed AFB on both ZN and RAF-AFB stainings and six of 25 cases showed AFB one each of ZN and RAF-AFB stainings, the resulting fifteen of 25 cases(60%) showed AFB with special stains. M. tuberculosis DNA was identified in 8 of 42 cases(l9%) by PCR, two cases of the positive eight cases and six cases without AFB stainings revealed positive findings on Tb-PCR. Although PCR is known a s a rapid, sensitive, and specific method for the diagnosis of intestinal tuberculosis, our study showed relatively low sensitivity and specificity, which might be caused by low numbers of organisms in the specimen and/or inadequate specimen. Therefore, for the detection of M. tuberculosis, diagnostic accuracy will be increased when both AFB stain and PCR are determined.

유방조직에서 티로신 활성효소 수용체인 EphA2, c-met 및 c-erbB-2의 발현

민수기,조현득,조성진,박혜림,신형식,박영의,염범우 대한병리학회 2005 Journal of Pathology and Translational Medicine Vol.39 No.1

Background : Tyrosine kinase receptor (TKR) is an important protein for normal-development, growth and tumorigenesis in human tissues. The purpose of this study was to evaluate the effect of TKR in the progression of breast cancer. Methods : The expressions of EphA2, c-met and c-erbB-2 were examined, by using immunohistochemical methods and RT-PCR, in samples of breast tissue that included 111 samples of normal epithelium, 34 samples of ductal carcinoma in situ (DCIS), and 109 samples of invasive ductal carcinomas (IDC). The results were compared with the prognostic parameters of breast cancer including the tumor grade, growth pattern, lymph node metastasis and the expressions of ER, PR, p53 and Ki-67. Results : The protein expressions of the three TKRs were higher in DCIS and IDC than in normal epithelium. The protein expression of EphA2 was correlated with a tumor grade, a labeling index of Ki-67, and the protein expression of c-met. Overexpression of c-erbB-2 was correlated with lymph node metastasis. The mRNA levels of the three TKRs were correlated with each other in normal tissue and IDC. The level of c-met mRNA was higher in the low grade tumors. Conclusions : The three TKRs may play roles in the tumorigenesis of human breast cancer. The overexpressions of EphA2 and c-erbB-2 may be a poor prognostic parameter in breast cancers.

전립선암 진단에서 P504S와 34βE12 면역염색의 유용성

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

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.