Expression of Claudin-1 and -7 in Clear Cell Renal Cell Carcinoma and Its Clinical Significance

신홍일,김병훈,장혁수,김천일,정혜라,박철희 대한비뇨의학회 2011 Investigative and Clinical Urology Vol.52 No.5

Purpose: We investigated the correlations between the expression of claudin-1 and claudin-7 in clear cell renal cell carcinoma (clear cell RCC) and clinical parameters. Materials and Methods: The subjects of this study were 119 patients with confirmed clear cell RCC between January 2000 and December 2007. Their RCC tissues were immunohistochemically stained for claudin-1 and claudin-7. The correlations between the expression of claudin and parameters such as sex, age, body mass index (BMI), tumor size, TNM stage, Furhman nuclear grade, postoperative distant metastasis, and cancer-specific survival were analyzed. Results: Among the total 119 subjects, claudin-1 was expressed in 18 (15.1%) and claudin-7 in 31 (26.1%). Claudin-1 was expressed in patients who were older (p=0.007), who had a greater tumor size (p=0.001), who had a higher pathologic T stage (p=0.009), who had preoperative distant metastasis (p=0.035), and who had a higher Furhman nuclear grade (p=0.004). Claudin-7 was expressed only in patients who had a higher Furhman nuclear grade (p=0.031). The risk of postoperative distant metastasis was associated with the expression of claudin-1 (p<0.001) but not with the expression of claudin-7 (p=0.668). The expression of claudin-1 and -7 was not associated with cancer-specific survival (p>0.05). Conclusions: In clear cell RCC, claudin-1 was expressed in patients who were older and who had a greater tumor size, who had higher T or M stages, and who had a higher Furhman nuclear grade. The expression of claudin-1 was associated with a higher risk of postoperative distant metastasis. Purpose: We investigated the correlations between the expression of claudin-1 and claudin-7 in clear cell renal cell carcinoma (clear cell RCC) and clinical parameters. Materials and Methods: The subjects of this study were 119 patients with confirmed clear cell RCC between January 2000 and December 2007. Their RCC tissues were immunohistochemically stained for claudin-1 and claudin-7. The correlations between the expression of claudin and parameters such as sex, age, body mass index (BMI), tumor size, TNM stage, Furhman nuclear grade, postoperative distant metastasis, and cancer-specific survival were analyzed. Results: Among the total 119 subjects, claudin-1 was expressed in 18 (15.1%) and claudin-7 in 31 (26.1%). Claudin-1 was expressed in patients who were older (p=0.007), who had a greater tumor size (p=0.001), who had a higher pathologic T stage (p=0.009), who had preoperative distant metastasis (p=0.035), and who had a higher Furhman nuclear grade (p=0.004). Claudin-7 was expressed only in patients who had a higher Furhman nuclear grade (p=0.031). The risk of postoperative distant metastasis was associated with the expression of claudin-1 (p<0.001) but not with the expression of claudin-7 (p=0.668). The expression of claudin-1 and -7 was not associated with cancer-specific survival (p>0.05). Conclusions: In clear cell RCC, claudin-1 was expressed in patients who were older and who had a greater tumor size, who had higher T or M stages, and who had a higher Furhman nuclear grade. The expression of claudin-1 was associated with a higher risk of postoperative distant metastasis.

Correlation between Claudins Expression and Prognostic Factors in Prostate Cancer

서경원,권영기,김병훈,김천일,장혁수,최미선,박철희 대한비뇨의학회 2010 Investigative and Clinical Urology Vol.51 No.4

Purpose: The purpose of this study was to evaluate the correlation between the expression of claudins and prognostic factors in patients with prostate cancer. Materials and Methods: The subjects of this study were 48 patients who had undergone surgery for prostate cancer. The Gleason score (6 or lower, 7 or higher), prostate-specific antigen (PSA) level, T stage, biochemical recurrence, local recurrence, and distant metastasis were compared according to the expression of claudin-1 and claudin-5 in prostate cancer. Results: In the group with a low expression of claudin-1, the Gleason score was 7 points or higher in 18 cases (82%) and 6 points or lower in 4 cases (18%). In the group with a high expression of claudin-1, the Gleason score was 7 points or higher in 13 cases (50%) and 6 points or lower in 13 cases (50%). Thus, the low-expression group had more cases with a Gleason score of 7 or higher (p=0.022). The group with a low expression of claudin- 5 also had more cases with a Gleason score of 7 or higher (p=0.011). The mean PSA values in the groups with a low and high expression of claudin-1 were 9.6 ng/ml and 5.6 ng/ml, respectively (p=0.007). A low expression of claudin-5 was also associated with a high PSA value (p=0.002). There was no statistical difference in the expression of claudin-1 and claudin-5 by T stage, biochemical recurrence, local recurrence, or distant metastasis. Conclusions: The low expression of claudin-1, claudin-5 was associated with a Gleason score of 7 or higher and a high PSA value in prostate cancer. Purpose: The purpose of this study was to evaluate the correlation between the expression of claudins and prognostic factors in patients with prostate cancer. Materials and Methods: The subjects of this study were 48 patients who had undergone surgery for prostate cancer. The Gleason score (6 or lower, 7 or higher), prostate-specific antigen (PSA) level, T stage, biochemical recurrence, local recurrence, and distant metastasis were compared according to the expression of claudin-1 and claudin-5 in prostate cancer. Results: In the group with a low expression of claudin-1, the Gleason score was 7 points or higher in 18 cases (82%) and 6 points or lower in 4 cases (18%). In the group with a high expression of claudin-1, the Gleason score was 7 points or higher in 13 cases (50%) and 6 points or lower in 13 cases (50%). Thus, the low-expression group had more cases with a Gleason score of 7 or higher (p=0.022). The group with a low expression of claudin- 5 also had more cases with a Gleason score of 7 or higher (p=0.011). The mean PSA values in the groups with a low and high expression of claudin-1 were 9.6 ng/ml and 5.6 ng/ml, respectively (p=0.007). A low expression of claudin-5 was also associated with a high PSA value (p=0.002). There was no statistical difference in the expression of claudin-1 and claudin-5 by T stage, biochemical recurrence, local recurrence, or distant metastasis. Conclusions: The low expression of claudin-1, claudin-5 was associated with a Gleason score of 7 or higher and a high PSA value in prostate cancer.

Prognostic Role of Claudin-1 Immunohistochemistry in Malignant Solid Tumors: A Meta-Analysis

표정수,김내유,조원진 대한병리학회 2019 Journal of Pathology and Translational Medicine Vol.53 No.3

Background: Although the correlation between low claudin-1 expression and worse prognosis has been reported, details on the prognostic implications of claudin-1 expression in various malignant tumors remain unclear. The present study aimed to elucidate the prognostic roles of claudin-1 immunohistochemistry (IHC) in various malignant tumors through a meta-analysis. Methods: The study included 2,792 patients from 22 eligible studies for assessment of the correlation between claudin-1 expression and survival rate in various malignant tumors. A subgroup analysis based on the specific tumor and evaluation criteria of claudin-1 IHC was conducted. Results: Low claudin-1 expression was significantly correlated with worse overall survival (OS) (hazard ratio [HR], 1.851; 95% confidence interval [CI], 1.506 to 2.274) and disease-free survival (DFS) (HR, 2.028; 95% CI, 1.313 to 3.134) compared to high claudin-1 expression. Breast, colorectal, esophageal, gallbladder, head and neck, and lung cancers, but not cervical, liver or stomach cancers, were significantly correlated with worse OS. Breast, colorectal, esophageal, and thyroid cancers with low claudin-1 expression were associated with poorer DFS. In the lower cut-off subgroup (< 25.0%) with respect to claudin-1 IHC, low claudin-1 expression was significantly correlated with worse OS and DFS. Conclusions: Taken together, low claudin-1 IHC expression is significantly correlated with worse survival in various malignant tumors. More detailed criteria for claudin-1 IHC expression in various malignant tumors are needed for application in daily practice.

유방암에서 Claudin-1과 ZO-1 단백 발현 감소와 임상-병리학적 인자와의 연관성

김민준(Min Joon Kim),차성재(Seong Jae Cha),박성일(Sung Il Park),박성준(Sung Jun Park),장인택(In Taik Chang),김범규(Beom Gyu Kim),최유신(Yoo Shin Choi),이태진(Tae Jin Lee) 대한외과학회 2007 Annals of Surgical Treatment and Research(ASRT) Vol.72 No.6

Purpose: Tight junction proteins are either over-expressed or suppressed in some cancers. These suppressions of claudin-1 and ZO-1 protein are known to have a significant relationship with the progression of breast cancer. The authors reviewed 42 cases of breast cancer and the staining status of claudin-1 and ZO-1 in order to evaluate Claudin-1 and ZO-1 as clinicopathologic risk factors. Methods: Immunohistological staining for Claudin-1 and ZO-1 was performed in 42 post-operative pathologically diagnosed infiltrating duct carcinoma specimens. The rate of expression was compared with the clinical record, the pathological diagnosis, the estrogen receptor and progesteron receptor status and the c-erbB2 gene to evaluate the protein expression-breast cancer progression relationship and to investigate the expressions of Claudin-1 and ZO-1 as a prognostic factors in breast cancer. Results: The claudin-1 and ZO-1 expressions were both decreased in all the post-operative specimens. The claudin-1 expressions were significantly decreased 100%, 82.4% and 66.7% as the histologic grade increased. The ZO-1 expressions were shown in 44.8% of the lymph node metastasis negative group and in 7.7% of the lymph node positive group. The expression of ZO-1 decreased by 53.3%, 28.6% and 0%, with statistical significance, as the stage increased. Conclusion: The claudin-1 expressions were decreased in the poorly differentiated group, i.e., a high histologic grade, and the ZO-1 expressions were decreased in the lymph node positive group and in the high stage cancer. This shows the possibility of Claudin-1 and ZO-1 as factors for tumorigenesis and progression and as prognostic factors in breast cancer.

Expression of Claudin-1, p53 and E-cadherin in Pseudoepitheliomatous Hyperplasia and Squamous Cell Carcinoma of the Head and Neck

최금하,임재홍,이주형,권근상,이호,박호성,정명자,문우성,은재순,이동근,장규윤 대한병리학회 2008 Journal of Pathology and Translational Medicine Vol.42 No.5

Background : Pseudoepitheliomatous hyperplasia (PEH) is a reactive proliferation of surface epithelium and can be confused with invasive squamous cell carcinoma (SCC) in head and neck biopsy specimens. To distinguish PEH from invasive SCC, immunohistochemical staining for claudin-1, E-cadherin and p53 was performed. Methods : Eighteen cases of PEH and 29 invasive SCC from head and neck lesions were immunostained and examined. Results : The invasive SCC showed increased staining of claudin-1 (p<0.001) and p53 (p<0.001) and decreased staining of E-cadherin (p=0.005) compared to the PEH specimens. The combined score calculated by adding the positive sum of claudin-1 and p53 and subtracting E-cadherin was useful for the differentiation of SCC from PEH (89.7% sensitivity and 88.9% specificity, p<0.001). Conclusions : The combined immunostaining for claudin-1, p53 and E-cadherin may help differentiate PEH from invasive SCC. The results of this study suggest that the increased expression of claudin-1 and p53 and the decreased expression of E-cadherin maybe markers for the aggressive growth of invasive SCC. Background : Pseudoepitheliomatous hyperplasia (PEH) is a reactive proliferation of surface epithelium and can be confused with invasive squamous cell carcinoma (SCC) in head and neck biopsy specimens. To distinguish PEH from invasive SCC, immunohistochemical staining for claudin-1, E-cadherin and p53 was performed. Methods : Eighteen cases of PEH and 29 invasive SCC from head and neck lesions were immunostained and examined. Results : The invasive SCC showed increased staining of claudin-1 (p<0.001) and p53 (p<0.001) and decreased staining of E-cadherin (p=0.005) compared to the PEH specimens. The combined score calculated by adding the positive sum of claudin-1 and p53 and subtracting E-cadherin was useful for the differentiation of SCC from PEH (89.7% sensitivity and 88.9% specificity, p<0.001). Conclusions : The combined immunostaining for claudin-1, p53 and E-cadherin may help differentiate PEH from invasive SCC. The results of this study suggest that the increased expression of claudin-1 and p53 and the decreased expression of E-cadherin maybe markers for the aggressive growth of invasive SCC.

결장 샘암종에서 Claudin-1, β-catenin과 E-cadherin의 발현

차은정 ( Eun Jung Cha ),장규윤 ( Kyu Yun Jang ),최하나 ( Ha Na Choi ),김경열 ( Kyung Ryul Kim ),최금하 ( Keum Ha Choi ),황성호 ( Sung Ho Hwang ),문우성 ( Woo Sung Moon ),강명재 ( Myoung Jae Kang ),이동근 ( Dong Geun Lee ) 대한내과학회 2008 대한내과학회지 Vol.74 No.2

목적: 부착 단백의 발현의 변화에 의한 세포-세포 부착의 파열은 종양 세포의 침윤과 전이에서 중요한 역할을 한다. 이에 이번 연구는 결장 샘암종에서 세포 부착 관련 물질인 claudin-1과 E-cadherin 및 β-catenin이 어떤 역할을 하는지 알아보고자 하였다. 방법: 47예의 결장 샘암종에서 claudin-1과 E-cadherin 및 β-catenin에 대한 면역조직화학적 염색을 시행하여 이들의 발현 양상을 관찰하고, 임상병리학적 인자들과의 상관관계를 분석하였다. 결과: Claudin-1의 발현은 결장 샘암종의 림프절 전이가 많을수록 유의하게 감소하였고(p=0.019), 침윤 부위 종양세포의 조직학적 분화도가 중분화를 보일 때 보다 저등급분화를 보일 때 유의하게 감소하였다(p=0.030). E-cadherin 과 β-catenin의 발현도 저등급분화 샘암종이 중분화 샘암종에 비해 유의한 감소를 보였다(각각 p=0.010, p=0.012). 또한 claudin-1, E-cadherin 및 β-catenin 중에서 2개 이상 단백질 발현의 감소는 샘암종의 조직학적 탈분화와 의미 있는 상관관계를 보였다(p=0.030). 결론: 본 연구의 결과는 결장 샘암종에서 claudin-1, E-cadherin과 β-catenin의 발현 감소가 샘암종의 진행과 종양의 탈분화와 관련이 있음을 시사한다. Background/Aims: Disruption of the cell-to-cell junction with changes in the expression of the junctional proteins is the hallmark of cancer invasion and metastasis. To investigate the roles of claudin-1, β-catenin and E-cadherin in adenocarcinoma of the colon, the relationship of their expression with clinical and pathological factors were examined. Methods: The expression of claudin-1, β-catenin and E-cadherin were examined in 47 cases of adenocarcinoma of the colon by immunohistochemical staining. Results: A reduced claudin-1 expression was associated with advanced lymph node metastasis (p=0.019) and histological dedifferentiation at the invasive front (p=0.030). A reduced expression of β-catenin and E-cadherin were correlated with histological dedifferentiation (p=0.012, p=0.010, respectively). The reduced expression of two or more proteins was correlated with the histological findings of dedifferentiation (p=0.030). Conclusions: These results suggest that loss of claudin-1, β-catenin and E-cadherin expression may be correlated with the progression of adenocarcinoma of the colon and associated with an advanced histological grade. (Korean J Med 74:146-153, 2008)

Expression Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

Alikanoglu, Arsenal Sezgin,Gunduz, Seyda,Demirpence, Ozlem,Suren, Dinc,Gunduz, Umut Riza,Sezer, Cem,Yildiz, Mustafa,Yildirim, Mustafa Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

Background: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. Materials and Methods: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. Results: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. Conclusions: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its well-known adhesion effect.

Airborne particulate matter increases MUC5AC expression by downregulating Claudin-1 expression in human airway cells

( Sang-su Kim ),( Cheol Hong Kim ),( Ji Wook Kim ),( Hsi Chiang Kung ),( Tae Woo Park ),( Yu Som Shin ),( Ju Deok Kim ),( Siejeong Ryu ),( Wang-joon Kim ),( Yung Hyun Choi ),( Kyoung Seob Song ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.10

CLB_2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates CLB_2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB_2.0. While the overexpression of claudin-1 decreased CLB_2.0-induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. CLB_2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetylcysteine inhibited CLB_2.0-induced IL-6 secretion, thereby decreasing the CLB_2.0-induced MUC5AC expression, whereas CLB_2.0-induced MUC1 expression increased. CLB_2.0 activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated the claudin-1 and MUC1 expressions, whereas it dramatically increased CLB_2.0-induced MUC5AC expression. These findings suggest that CLB_2.0-induced ERK1/2 activation acts as a switch for regulating inflammatory conditions though a ROS-dependent pathway. Our data also suggest that secreted IL-6 regulates CLB_2.0-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway. [BMB Reports 2017; 50(10): 516-521]

두경부 편평세포암에서 Claudin-1 발현의 예후인자적 의미

이진,김선우,이상혁,진성민,도성임,이현주 대한이비인후과학회 2021 대한이비인후과학회지 두경부외과학 Vol.64 No.5

Background and Objectives Claudin-1 (CLDN-1) is the major component of tight junctionsand functions in controlling cell to cell adhesion. Certain claudins were expressed aberrantlyand proved to have prognostic significance in various human cancers. However, its clinical significancehas been poorly understood in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the relationship between CLDN-1 expression and clinicopathologicparameters in HNSCC. Subjects and Method The surgical specimens of primary HNSCCs from a consecutive cohortof 91 patients were retrospectively collected. Immunohistochemical staining for CLDN-1was performed blindly by two pathologists. CLDN-1 staining intensity was scored semi-quantitativelyon a scale of 0 to 3 (0: negative; 1: weak; 2: moderate; 3: strong). For the statistical analysis,the expression levels were classified as low (negative and weak) and high (moderate and strong). Next, the association between CLDN-1 expression and clinicopathological features & clinicaloutcomes was analyzed. Results The increased CLDN-1 expression was significantly associated with lymphatic invasion(p=0.019). The expression level of CLDN-1 was not associated with pathological T stage,lymph node metastasis or recurrence. Kaplan-Meier analysis found that 3-year overall survival(OS) rate was 53% in patients with high level CLDN-1 expression and 74% in patients with lowlevel CLDN-1 expression. It also found that 5-year OS rate was 49% in patients with high levelCLDN-1 expression and 68% in patients with low level CLDN-1 expression. A significantly poorOS rate was recorded in patients with high level of CLDN-1 expression compared to patients withlow level CLDN-1 expression (p=0.022). Conclusion CLDN-1 may serve as useful prognostic marker in patients with HNSCCs.

황금 생물 전환 물질이 피부의 면역 기능과 Claudin-1에 미치는 영향

김현아 ( Hyo-na Kim ),윤미영 ( Mi-young Yun ) 한국미용학회 2016 한국미용학회지 Vol.22 No.6

The Scutellariae baicalensis Georgi of this study are to identify the effects of S. baicalin bio-conversion substance on atopy. The cultural technique of mycelium of red deokdari mushroom was applied into SB which is effective for atopic dermatitis. G/Baicalein was produced, which was composed of Baicalein-Aglycon and glucan formed from mycelium. The effect on immune functioning recovery and recovery mechanism of Claudin 1- mainly protein of TJ in Keratinocyte, which is composed of skin surface-was confirmed with in vitro and in vivo. This result proved effective in treating atopic dermatitis. When number of immunocyte in back dermal tissue in the test of in vivo was observed, it was meaningly reduced in group with G/Baicalein more than that of comparison group and SB. Specially, in the test to learn the effect of changes in number of immunocyte, the number of CD4⁺, CD8⁺, CD11b⁺/Gr-1⁺ cells was decreased significantly. When Claudin-1 was observed after cutting skin tissue, Claudin-1 with red fluorescent color was increased in SB and G/ Baicalein group compared with control group. Especially, Claudin-1 was remarkably increased in G/Baicalein compared with control group. According to the above result, G/Baicalein increased expression ratio of Claudin 1- mainly protein of TJ, and immune functioning recovery was confirmed. In conclusion, if G/Baicalein will be developed as substance of cosmetics for atopic dermatitis and applied for skin treatment, it will be available effectively at the treatment for atopic dermatitis.