Clinical Significance of Dysadherin Expression in Gastric Cancer Patients

Shimada, Yutaka; Yamasaki, Seiji; Hashimoto, Yuichi; Ito, Takahiro; Kawamura, Jun; Soma, Toshiya; Ino, Yoshinori; Nakanishi, Yukihiro; Sakamoto, Michiie; Hirohashi, Setsuo; Imamura, Masayuki

doi:10.1158/1078-0432.ccr-0633-03

Cited by 48 publications

(51 citation statements)

References 22 publications

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“…In invasive ductal carcinoma, as reported in this study, there is an increase in dysadherin expression, which is not related to E-cadherin expression. This lack of association has also been reported in pancreatic, primary colorectal and gastric carcinomas (Shimamura et al, 2003;Shimada et al, 2004b;Batistatou et al, 2005). Furthermore, in the in situ ductal carcinoma dysadherin was not expressed.…”

Section: Dysadherin In Breast Carcinomasupporting

confidence: 54%

“…For the purposes of statistical analysis, as described previously (Shimada et al, 2004b;Batistatou et al, 2005), when more than 50% of tumour cells were stained for dysadherin, the tumour was evaluated as 'positive dysadherin expression (Dys( þ ))'. When less than 50% of tumour cells were stained for dysadherin, the tumour was evaluated as 'negative dysadherin expression (Dys(À))'.…”

Section: Evaluation Of the Stainingmentioning

confidence: 99%

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In breast carcinoma dysadherin expression is correlated with invasiveness but not with E-cadherin

et al. 2007

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Reduction/loss of E-cadherin is associated with the development and progression of many epithelial tumours. Dysadherin, recently characterised by members of our research team, has an anti-cell -cell adhesion function and downregulates E-cadherin in a posttranscriptional manner. The aim of the present study was to study the role of dysadherin in breast cancer progression, in association with the E-cadherin expression and the histological type. We have selected ductal carcinoma, which is by far the most common type and lobular carcinoma, which has a distinctive microscopic appearance. Dysadherin and E-cadherin expression was examined immunohistochemically in 70 invasive ductal carcinomas, no special type (NST), and 30 invasive lobular carcinomas, with their adjacent in situ components. In ductal as well as in lobular carcinoma dysadherin was expressed only in the invasive and not in the in situ component, and this expression was independent of the E-cadherin expression. Specifically, all 10 (100%) Grade 1, 37out of 45(82.2%) Grade 2 and six out of 15 (40%) Grade 3 invasive ductal carcinomas showed preserved E-cadherin expression, while 'positive dysadherin expression' was found in six out of 10 (60%) Grade 1, 34 out of 45(75.5%) Grade 2 and all 15 (100%) Grade 3 neoplasms. None of the 30 infiltrating lobular carcinomas showed preserved E-cadherin expression, while all the 30 infiltrating lobular carcinomas exhibited 'positive dysadherin expression'. Dysadherin may play an important role in breast cancer progression by promoting invasion and, particularly in lobular carcinomas, it might also be used as a marker of invasion. Recent advances into molecular pathology of breast cancer have refined diagnostic accuracy and classification systems of the most common malignant neoplasm of women, rendering personalised therapy more possible. Today, there is a plethora of molecular genetic data that indicate differences in pathogenesis between the various types of breast carcinomas and thus support their categorisation, to the patient benefit. The demonstration of lack of E-cadherin expression in lobular neoplasms has had a sound impact with practical applications (Mastracci et al, 2005) In about half of lobular carcinomas, loss of E-cadherin involves genetic changes, that is loss of heterozygosity (LOH) at 16q22.1, while in the other half epigenetic events are involved (Knudsen and Wheelock, 2005;Mastracci et al, 2005). Ductal carcinomas, on the other hand, express E-cadherin, albeit in reduced levels and/or in abnormal cellular locations (Knudsen and Wheelock, 2005). Reduction/loss of E-cadherin has been associated with the development and progression of many epithelial neoplasms. Aberrant E-cadherin expression (heterogeneous, cytoplasmic, or absent) has been detected immunohistochemically in several cancers, including head and neck carcinoma, gastric adenocarcinoma, lobular breast carcinoma, lung cancer, colorectal carcinoma, prostate adenocarcinoma, pancreatic, and bladder cancer (Becker et

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Section: Dysadherin In Breast Carcinomasupporting

confidence: 54%

Section: Evaluation Of the Stainingmentioning

confidence: 99%

In breast carcinoma dysadherin expression is correlated with invasiveness but not with E-cadherin

et al. 2007

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“…12 Dysadherin is expressed in a variety of cancer cells and malignant melanoma cells. [12][13][14][15][16]28 To date, no investigation into dysadherin expression in sarcomas has been reported. 29 and epithelial membrane antigen.…”

Section: Discussionmentioning

confidence: 99%

“…Tumors were classed as dysadherinpositive when more than 50% of the cells were stained. [13][14][15][16] The MIB-1-labeling index was estimated as the percentage of Ki-67-positive cells based on a count of 1000 tumor cells within the tumor. Dysadherin and E-cadherin expression were evaluated by four of the authors (TI, YO, TH and MT) without any knowledge of the clinical features in each case.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

et al. 2006

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Dysadherin is a cancer-associated cell membrane glycoprotein, which downregulates E-cadherin and promotes metastasis. We studied the clinicopathological features in 72 cases of epithelioid sarcoma and in six cases of malignant rhabdoid tumor, and also assessed the immunohistochemical expression of dysadherin, E-cadherin and MIB-1 in epithelioid sarcoma and malignant rhabdoid tumor cases. In addition, we compared dysadherin mRNA expression between epithelioid sarcoma and malignant rhabdoid tumor cell lines, using RT-PCR and realtime quantitative RT-PCR analysis. Immunohistochemical dysadherin expression was more frequently observed in proximal-type epithelioid sarcoma (71%) in comparison with distal-type epithelioid sarcoma (36%) (P ¼ 0.037). Furthermore, seven proximal-type epithelioid sarcoma cases mimicking malignant rhabdoid tumor (histologically classified as the large cell type, accompanied by frequent rhabdoid cells and located in deep soft tissue) were all positive for dysadherin (100%), whereas dysadherin expression was not detected at all in any of the true six malignant rhabdoid tumors (0%). Cell lines established from proximal-type epithelioid sarcoma revealed significantly higher levels of dysadherin mRNA expression, compared with the levels seen in malignant rhabdoid tumor cell lines by real-time quantitative RT-PCR (P ¼ 0.0433). Epithelioid sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P ¼ 0.001). In multivariate analysis, dysadherin immunopositivity (P ¼ 0.0004) was one of the two independent adverse prognostic factors. We conclude that dysadherin expression in epithelioid sarcoma is a significant poor prognostic factor and that it is a powerful diagnostic marker for distinguishing epithelioid sarcoma, including the proximal-type epithelioid sarcoma, from malignant rhabdoid tumor. In epithelioid sarcoma, especially in proximal-type epithelioid sarcoma, increased cell disadhesion and motility by dysadherin plays an important role to acquire aggressive biological behavior. However, in malignant rhabdoid tumor, cell growth cycle that is regulated by hSNF5/INI1 gene seems to be critical to lethal biological behavior rather than dysadherin.

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“…6-8 While the role of dysadherin in gastric cancer has been studied in detail, in oesophageal cancer its role remains mainly unexplored. 7,9,10 In a clinical study from Shimada et at 11 expression of dysadherin was studied in 117 patients with oesophageal squamous cell carcinoma of all stages. The correlation between immunohistochemically evaluated dysadherin expression with patient clinicopathological data was studied.…”

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confidence: 99%

Dysadherin: A Novel Oncogenic Molecular Biomarker in Oesophageal Cancer

Charalabopoulos¹,

Liakakos²

2017

Cancer Stud Mol Med Open J

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Dysadherin or FXYD5 is a transmembrane glycoprotein, identified for the first time in 2002 by a team of Japanese researchers. 1 Although, it is generally accepted that most of its action is derived from the increased maximal velocity (V max ) of the Na + -K + -ATPase that promotes, there are several actions of dysadherin that cannot be attributed to its interaction with the Na + -K + -ATPase. 2 Dysadherin is a well-described cancer-associated protein and a potential oncogenic molecular target with promising future significances. It has been distinctly shown, in both the cases of in vivo and in vitro studies, that when expressed in malignant tumours, it signifies augmented tumorigenesis with enhanced metastatic potential and haematogenous spread and is thus linked to poor prognosis. 3,4 On the contrary, studies based on human cancer cell lines have demonstrated that introduction of small interfering RNA (siRNA) against dysadherin leads to downregulation and subsequent membranous underexpression of dysadherin, instigating accordingly decreased collective and individual cell motility with subsequent inhibition of tumour aggressiveness and metastatic potential. 5 Its main interaction in carcinogenesis takes place with E-cadherin (epithelial cadherin); the most important adhesion molecules of the cadherin family. E-cadherin is involved in cancer development in more than 90% of human cancers, as most are carcinomas of epithelial origin. E-cadherin mediates homophilic cell-to-cell adhesion and promotes adherence between neighboring epithelial cells; its decreased cellular expression is hence associated with enhanced disconnection and dispersal of epithelial cells, promoting cell detachment from the primary lesion and consequently exhibiting increased metastatic potential.Dysadherin and its closely related E-cadherin, has been studied in various cancers and its correlation with cancer aggressiveness and poor prognosis has been collectively and undoubtedly reported. 6-8 While the role of dysadherin in gastric cancer has been studied in detail, in oesophageal cancer its role remains mainly unexplored. 7,9,10 In a clinical study from Shimada et at 11 expression of dysadherin was studied in 117 patients with oesophageal squamous cell carcinoma of all stages. The correlation between immunohistochemically evaluated dysadherin expression with patient clinicopathological data was studied. Oesophageal tumours with expression of dysadherin, displayed worse prognosis in comparison to tumours negative for dysadherin. When dysadherin positivity was combined with absence of E-cadherin expression, a statistically significant detrimental effect was exhibited in that patient group, revealing the worst prognosis of all patient groups. In the group of oesophageal tumours expressing both dysadherin and E-cadherin, prognosis was slightly better, but still poorer compared to the group of tumours that displayed no dysadherin expression. In accordance to what has been shown in relevant studies exploring the role of dysadherin in extraoesophage...

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Clinical Significance of Dysadherin Expression in Gastric Cancer Patients

Cited by 48 publications

References 22 publications

In breast carcinoma dysadherin expression is correlated with invasiveness but not with E-cadherin

In breast carcinoma dysadherin expression is correlated with invasiveness but not with E-cadherin

Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

Dysadherin: A Novel Oncogenic Molecular Biomarker in Oesophageal Cancer

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