ALK-Positive Renal Cell Carcinoma in a Large Series of Consecutively Resected Korean Renal Cell Carcinoma Patients

이철,문경철,박정환,서자희,남경한 대한병리학회 2013 Journal of Pathology and Translational Medicine Vol.47 No.5

Background: Recently, there have been a few reports of renal cell carcinoma (RCC) cases with anaplastic lymphoma kinase (ALK) gene fusion. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases. Methods: We screened 829 RCCs by ALK immunohistochemistry, and performed fluorescence in situ hybridization analysis using ALK dual-color break-apart rearrangement probe. Histological review and additional immunohistochemistry analyses were done in positive cases. Results: One ALK-positive case was found. Initial diagnosis of this case was papillary RCC type 2. This comprises 0.12% of all RCCs (1/829) and 1.9% of papillary RCCs (1/53). This patient was a 44-year-old male with RCC found during routine health check-up. He was alive without evidence of disease 12 years after surgery. The tumor showed a papillary and tubular pattern, and showed positivity for CD10 (focal), epithelial membrane antigen, cytokeratin 7, pan-cytokeratin, PAX-2, and vimentin. Conclusions: We found the first RCC case with ALK gene rearrangement in Korean patients by ALK immunohistochemistry among 829 RCCs. This case showed similar histological and immunohistochemical features to those of previous adult cases with ALK rearrangement, and showed relatively good prognosis.

만성 간질환 환자의 간조직에서 Sandwitch In Situ Hybridization 에 의한 B 형 간염바이러스의 검출

이상혁(Sang Hyuk Lee),김세종(Sei Jong Kim),박창수(Chang Soo Park),김현수(Hyun Soo Kim) 대한내과학회 1997 대한내과학회지 Vol.52 No.6

N/A Objectives: In situ hybridization(ISH) is widely applied as an effective method to detect the positive signal in the preservation of histological architecture with high specificity. The purpose of this study is to evaulate the clinical availability of SISH(sand-witch in situ hybridization) using HBsAg mRNA probe in biopsy specimen of patients with chronic liver disease. Methods: SISH was employed to detect the HBsAg mRNA & DNA in 127 cases of chronic liver diseases and the results were compared with those obtained by immunohistochemistry and enzyme immunoassay methods, Results: The HBsAg mRNA & DNA by SISH and the HBsAg by immmunohistochemistry were detected in 94 cases(92.2%) and 86 cases(84.3%) of 102 HBsAg seropositive cases, respectively. The detection of HBsAg mRNA & DNA by SISH was identified in 8 cases of 25 HBsAg seronegative cases of chronic liver disease, and the HBsAg by immunohistochemistry in 1 case. The detection rates of HBsAg mRNA & DNA by SISH were 78.3% in chronic persistent hepatitis, 81.7% in chronic active hepatitis, 87.5% in liver cirrhosis, and 70.6% in hepatocellular carcinoma. The positive rates of HRsAg by immunohistochemistry were 56.5% in chronic persistent hepatitis, 71.8% in chronic active hepatitis, 87.5% in liver cirrhosis, and 52.9% in hepatocellular carcinoma. The detection of HBsAg mRNA & DNA by SISH is more sensitive than that of HBsAg by immunohistochemistry. Conclusion: SISH using HBsAg mHNA probe is a useful and sensitive method to detect HBV in chronic liver disease, and it is more sensitive than immunohistochemistry.

흰쥐 뇌조직의 발달에 따른 Guanine Deaminase의 발현 양상

이경훈,최재선,이화영,신동훈,강태천,김현준,조사선,백상호,5성연선,박주배 대한해부학회 1999 Anatomy & Cell Biology Vol.32 No.2

염증성 치은 상피와 치낭의 표피성장인자 수용체의 발현 및 실험적 치아이동에 미치는 영향에 관한 연구

김영호,배창 대한치과교정학회 1997 대한치과교정학회지 Vol.27 No.2

동소 mRNA 보합결합법과 면역조직 화학적 염색법을 이용하여 정상 치은 상피와 염증성 치은 상피의 표피성장인자 수용체의 발현을 관찰하여 치은 상피의 염증에 있어서 표피성장인자 수용체의 역할을 연구하고, 타액에 노출되지 않는 치낭 조직에 있어서 표피성장인자 수용체의 발현을 관찰하여 다음과 같은 결과를 얻었다. 1. 동소 mRNA 보합결합법상 정상 치은 상피에서 EGFR mRNA는 거의 기저세포층에 국한되어 나타났으며, 극세포층은 약양성을 보였고 과립층과 각화층에서는 발현되지 않았다. 2. 면역조직 화학적 염색법상 정상 치은 상피에서 EGFR 단백은 거의 각화층과 과립층에국한되어 나타났으며, 극세포층은 약양성을 보였고 기저세포층에서는 발현되지 않았다. 3. 동소 mRNA 보합결합법상 염증성 치은 상피에서 EGFR mRNA는 각화층을 제외한 전층에 걸쳐서 균일하게 분포하였다. 4. 면역조직 화학적 염색법상 염증성 치은 상피에서 EGFR 단백은 기저세포층에서 각화층에 걸쳐서 균일하게 분포하였다. 5. 치낭 조직에서는 동소 mRNA 보합결합법과 면역조직 화학적 염색법 모두에서 Malassez 상피세포 잔존물에 강하게 염색이 되었고, 그 외의 주위 조직에서는 발현되지 않았다. 이상의 결과에서 볼 때, 염증성 치은 상피에서 EGFR의 과발현과 치낭 조직의 Malassez 상피세포 잔존물에서 다량의 EGFR이 존재하는 것으로 미루어, 이는 구강 환경에 가해질 수 있는 손상에 대하여 생체의 항상성을 유지하기 위한 반응으로 여겨진다. Epidermal growth factor(EGF), a single chain polypeptide of 53 amino acids with a molecular weight of 6,045 Da, was first isolated from the male mouse submandibular glands. EGF stimulates cellular proliferation and differentiation in several tissues and accelerates the rate of wound healing. EGF is bound to the specific receptor(EGFR) on the cell membrane of its target cell. EGFR is a transmembrane glycoprotein with a molecular weight of 170,000 Da and is detectable on a large variety of cell types. The authors investigated the expression of EGFR in the normal and inflamed human gingival epithelium to study the role of FGFR in the inflammation of the gingival epithelium, and the expression of EGFR in the dental follicle by using in situ mRNA hybridization and immunohistochemistry. The results were as follows; 1. The expression of EGFR mRNA in the normal gingival epithelium on in situ mRNA hybridization was mainly localized on the basal cell layer, and the spinous layer was weakly positive. The granular and cornified layers ere negative. 2. The expression of EGFR protein in the normal gingival epithelium on immunohistochemistry was localized on the cornified and granular layers, and the spinous layer was weakly positive. The basal cell layer was completely negative. 3. The expression of EGFR mRNA in the inflamed gingival epithelium on in situ mRNA hybridization was evenly and homogeneously distributed in the whole layers of the gingival epithelium except the cornified layer. The staining intensity appeared to increase progressively from the basal cell layer to the cornified layer. 4. The expression of EGFR protein in the inflamed gingival epithelium on immunohistochemistry was evenly and homogeneously distributed in the whole layers of the gingival epithelium. The staining intensity appeared to increase progressively from the cornified layer to the basal cell layer. 5. Strong positive reaction was seen in the epithelial cell rests of Malassez, whereas only background staining was seen in other cells of the dental follicle. In conclusion, the up-regulation of EGFR in the inflamed gingival epithelium and the high amounts of EGFR in the epithelial cell rests of Malassez in the dental follicle can be regarded as responses to the possible damages to the oral environment to maintain the homeostatic conditions.

Methylation and Immunoexpression of p16INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16INK4a Hypermethylation in Plasma by Real-Time PCR

이재준,조은윤,고은경,조준훈,박하영,이정언,남석진,김덕환 대한병리학회 2012 Journal of Pathology and Translational Medicine Vol.46 No.6

Background: The p16INK4a gene methylation has been reported to be a major tumorigenic mechanism. Methods: We evaluated the methylation status of the p16INK4a genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16INK4a DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay. Results: The frequencies of p16INK4a methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90),respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16INK4a was significantly higher in the cancer patients than the normal controls (p<0.001). Conclusions: High p16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16INK4a promoter methylation in both invasive and intraductal carcinomas, suggesting it maybe involved in the pathogenesis of breast cancer.

Expression of Leptin and Its Receptor in Rat Ovary

김명신,양현원,권혁찬,황경주,윤현숙,박금자,김세광,윤용달 한국발생생물학회 1998 발생과 생식 Vol.2 No.2

비만유전자 산물인 leptin은 지방 조직에서 생성되어 혈액으로 분비되며, 신진대사, 식욕, 체열 등을 조절하여 비만의 억제 조절 물질로 작용하는 것으로 알려져 있다. 또한 leptin은 비만 뿐만 아니라 생식 생리와도 관련이 있는 것으로 보이며, 이러한 leptin의 작용이 난소에 직접적인지 혹은 시상하부나 뇌하수체를 매개로 하는지는 아직 정확하게 밝혀지지 않고 있으며, 난소에서의 leptin 및 leptin 수용체의 발현 양상에 대한 연구 또한 미진 Leptin, the product of the obese gene, is produced by adipose tissue and is known to be a hormone concerned with regulation of appetite and metabolism. Recent reports have shown that leptin is associated not only with obesity but also with female reproduction, but it has not yet been ascertained whether leptin acts directly on the ovaries or indirectly via the hypothalamus or pituitary pathway. The object of this study is to determine the expression of leptin and its receptor in the ovaries of 3 and 8 weeks old rats by immunohistochemistry and RT-PCR. In the ovaries of 3 and 8 weeks old rats, leptin was stained in the theca cells and portions of granulosa cells of atretic follicles, whereas leptin receptors was stained in interstitial cells and ova of preantral follicles. The RT-PCR results showed that leptin receptor mRNA was expressed in the ovaries of both immature and adult rats, while leptin mRNA was not. In conclusion, leptin mRNA was not expressed in the ovaries, however, leptin was detected by immunohistochemistry. Compared to leptin itself, leptin receptors in the ovaries were ascertained by both RT-PCR and immunohistochemistry. These results suggest that leptin is related to the regulation of the physiological functions of the ovaries.

Correlation of Clinical and Immunohistochemical Diagnosis in Patients with Pituitary Adenomas

Park, Sung-Ku,Jung, Shin,Jung, Tae-Young,Kim, In-Young,Kim, Soo-Han,Kang, Sam-Suk The Korean Neurosurgical Society 2007 Journal of Korean neurosurgical society Vol.41 No.6

Objective: Pituitary adenomas are common neurological lesions believed to account for 10% to 15% of all primary brain tumors. There can be diagnostic confusion due to discordance of the preoperative endocrine and the postoperative immunohistochemical diagnosis. In this study, the rate of discordance between preoperative and postoperative findings and their clinical implications were investigated. Methods: From March 2005 to March 2006, 26 patients who underwent surgery for a pituitary adenoma were enrolled in this study. The preoperative pituitary hormone level and postoperative immunohistochemical results were compared and analyzed. Results: The median age of the patients was 38 years [range 15-66 years]. The male to female ratio was 8 to 18. The endocrine evaluation showed 16 hormonally-active and 10 hormonally-inactive adenomas. The immunohistochemical findings showed : 13 prolactin-positive, 1 GH-positive, 1 FSH-positive, 8 pleurihormone-positive and 3 stain-negative adenomas. The percentage of discordance observed between the preoperative endocrine and postoperative immunohistochemical diagnosis was 54%. Nine of 10 endocrine non-functioning adenomas showed : 3 PRL positive, 1 GH positive, 2 PRL+GH positive, 1 TSH+FSH positive, 1 FSH+ACTH+PRL positive and 1 FSH+LH+PRL positive adenomas by immunohistochemistry. Three endocrine PRL+GH secreting adenomas showed 2 PRL positive and 1 FSH+GH positive by immunohistochemistry. One endocrine PRL secreting and 1 GH secreting adenoma showed 1 PRL+ TSH positive and 1 GH+PRL positive by immunohistochemistry, respectively. The diagnosis of the other 12 pituitary adenomas showed concordance. Conclusion : The results of this study showed 54% discordance rate between the preoperative endocrine and postoperative immunohistochemical diagnosis for pituitary adenomas.

Investigation of the Roles of Cyclooxygenase-2 and Galectin-3 Expression in the Pathogenesis of Premenopausal Endometrial Polyps

Esin Kasap,Serap Karaarslan,Esra Bahar Gur,Mine Genc,Nur Sahin,Serkan Güclü 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.3

Background: The pathogenesis and etiology of endometrial polyps has not been elucidated. In this study, we aimed to examine the pathogenic mechanisms of endometrial polyp development using immunohistochemistry. We evaluated the expression of galectin-3 and cyclooxgenase-2 (COX-2) during the menstrual cycle in premenopausal women with endometrial polyps or normal endometrium. Methods: Thirty-one patients with endometrial polyps and 50 healthy control patients were included in this study. The levels of expression of COX-2 and galectin-3 were studied by immunohistochemistry. Results: The percentage of COX-2–positive cells and the intensity of COX-2 staining in the endometrium did not vary during the menstrual cycle either in the control group or in patients with endometrial polyps. However, expression of galectin-3 was significantly lower in endometrial polyps and during the proliferative phase of the endometrium compared with the secretory phase. Conclusions: Our data suggests that the pathogenesis of endometrial polyps does not involve expression of COX-2 or galectin-3.

개에서 디스템퍼 바이러스와 톡소플라즈마의 혼합 감염

강홍원,강상철,양형석,배종희,김재훈 한국임상수의학회 2004 한국임상수의학회지 Vol.21 No.1

A 3 month-old male dog with clinical signs of anorexia, soft stool, ocular and nasal discharge, cough and respiratory distress was submitted to the Cheju National University for diagnosis. At necropsy, tan to purple-red sublobar to lobar consolidations were presented in apical and cardiac lobe of lung. Histopathologically, severe diffuse bronchointerstitial pneumonia with necrotic bronchiolitis was noted in the lung. The demyelinating encephalitis and astrocytosis were presented in cerebellum and cerebrum. Numerous round, ovoid or cluster of tachyzoites were also identified in alveolar lumen, alveolar wall and cytoplasm of macrophages in the lung. The orgasnisms were demonstrated as Toxoplasma (T) gondii by immunohistochemistry. Intranuclear or intracytoplasmic eosinophilic inclusion bodies were seen in the glial cells of the cerebellum. Canine distemper virus (CDV) specific antigens were demonstrated in the cerebellum by the immunohistochemistry. In our knowledge, this is believed to be the first confirmed report of co-infection of CDV and T gondii in dog in Korea.

Gitelman 증후군 환자에서 면역조직화학법으로 확인한 원위세관 sodium-chloride cotransporter (NCCT)의 결손

장혜련 ( Hye Ryoun Jang ),허남주 ( Nam Ju Heo ),손민정 ( Min Jung Son ),이재욱 ( Jay Wook Lee ),이정환 ( Jeong Hwan Lee ),전은실 ( Un Sil Jeon ),신성준 ( Sung Jun Shin ),나기영 ( Ki Young Na ),주권욱 ( Kwon Wook Joo ),이정상 ( Jun 대한내과학회 2005 대한내과학회지 Vol.69 No.6

목적 : Gitelman 증후군은 저포타시움혈증, 대사성 알칼리증, 고레닌혈증, 고알도스테론혈증, 요 중 칼슘 배설의 저하 및 저마그네슘혈증을 특징으로 하는 유전성 질환이다. 이는 원위세관 sodium-chloride cotransporter (NCCT)의 유전자 돌연변이에 의하여 발생하는 것으로 알려져 있으나 사람의 신조직에서 NCCT 결손이 증명된 바는 없었다. 방법 : 저자들은 임상적으로 Gitelman 증후군이 의심되는 환자에서 이뇨제를 이용한 신청소율 검사와 유전자 검사를 시행하였고, 이를 통하여 감별진단한 Gitelman 증후군 환자의 신조직에서 인간 NCCT에 대한 토끼 다클론 항체를 이용한 면역조직화학법을 시행하였다. 신세포암으로 신적출술을 시행 받은 환자의 정상 신조직과 전해질 이상이 없었던 사구체신염 환자의 신조직을 각각 정상 대조군과 질환 대조군으로 하였다. 결과 : 대상 환자는 저포타시움혈증과 대사성 알칼리증, 저마그네슘혈증 및 요 중 칼슘 배설의 저하를 보였다. Bartter 증후군과 감별을 위하여 furosemide 및 hydrochlorothiazide를 이용한 신청소율 검사를 시행하였다. 수분 부하를 시행한 기저치(86.1%)에 비해서 furosemide를 투여한 후 distal fractional chloride reabsorption이 감소하였으나(9.7%) hydrochlorothiazide 투여 후에는 변화가 없었다(81.4%). 유전자 검사 결과 SLC12A3 유전자의 돌연변이(S967F)가 발견되었다. 신조직에서 면역조직화학법을 시행한 결과 정상 및 질환 대조군에서는 원위세관 세포의 내강 막 쪽에 NCCT가 뚜렷이 염색되었으나, Gitelman 증후군에서는 원위세관 세포의 NCCT에 대한 면역 반응성이 관찰되지 않았다. 반면에 Na/K-ATPase, Na-K-2Cl cotransporter, calbindin-D28K는 대조군과 대상 환자의 신조직에서 모두 관찰되었다. 결론 : 기능적 검사로 진단된 Gitelman 증후군 환자의 신조직에서 NCCT의 결함을 면역조직화학법으로 확인하였다. Background : Gitelman`s syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is known to be caused by a mutation of SLC12A3 gene coding the sodium-chloride cotransporter (NCCT) in the distal tubule. The defect of NCCT in human renal tissues has not been investigated, and we tested whether the defect of NCCT can be detected in renal tissue of a patient with Gitelman`s syndrome by using immunohistochemistry. Methods : In an adult patient with Gitelman`s syndrome, blood and urine samples were collected for measurement of biochemical parameters. Renal clearance study and gene analysis were performed. Immunohistochemistry was performed on the renal tissue of the patient using a rabbit polyclonal antibody directed against a synthetic peptide corresponding to a portion in the amino terminal tail for human NCCT. Normal human renal tissues from surgical nephrectomy due to renal cell carcinoma and renal biopsy tissues from patients with glomerulonephritis but without any electrolyte disturbance were used as controls. Results : The patient had hypokalemic metabolic alkalosis, hypocalciuria and hypomagnesemia. Renal clearance study revealed a decrease in distal fractional chloride reabsorption after the administration of furosemide. SLC12A3 gene mutation (S967F) was found by direct sequencing method. Immunohistochemistry showed the absence of NCCT staining in the renal tissue of the patient. On the other hand, the immunostaining of other transporters was all positive in renal tissues from both Gitelman`s syndrome patients and controls. Conclusions : We report the absence of intact NCCT in the renal tissue of a Gitelman`s syndrome patient.(Korean J Med 69:642-650, 2005)