Prognostic significance of dysadherin expression in advanced colorectal carcinoma

Aoki, Shigeo; Shimamura, Takeshi; Shibata, Tatsuhiro; Nakanishi, Yukihiro; Moriya, Yoshihiro; Sato, Yasunori; Kitajima, Masaki; Sakamoto, Michiie; Hirohashi, Setsuo

doi:10.1038/sj.bjc.6600778

Cited by 47 publications

(62 citation statements)

References 34 publications

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“…Until now, dysadherin expression has been studied in colorectal, pancreatic, gastric, esophageal, tongue and thyroid carcinomas, as well as in cervical squamous cell carcinomas and cutaneous malignant melanomas (Aoki et al, 2003;Sato et al, 2003;Shimamura et al, 2003Shimamura et al, , 2004Nakanishi et al, 2004;Shimada et al, 2004a, b;Wu et al, 2004;Nishizawa et al, 2005). In all these cancer types, a general phenomenon is that dysadherin expression seems to reflect tumour aggressiveness, being furthermore a marker of poor prognosis when considered alone or/and in combination with downregulation of E-cadherin.…”

Section: Discussionmentioning

confidence: 99%

“…Staining for both antibodies was graded as 0, if no cells were stained, 1 þ if 1 -25% of cells were stained, 2 þ if 26 -49% of cells were stained, 3 þ if 50 -74% of cells were stained, and 4 þ if 475% of cells were stained. For the purposes of statistical analysis, samples that showed weak intensity and/or low frequency of expression (o50%) were grouped together as 'Low dysadherin or 'Low E-cadherin', as previously described (Aoki et al, 2003). Staining for E-cadherin was more heterogeneous, since in many cases only granular cytoplasmic staining was noted, while in others a weak incomplete membranous staining was observed.…”

Section: Evaluation Of the Stainingmentioning

confidence: 99%

“…So far reports on the function and expression of dysadherin in tumour samples are limited. This novel cancer-associated protein has been detected in gastric, colorectal, pancreatic, esophageal, thyroid tongue, and cervical carcinomas as well as in malignant melanoma and associated with tumour aggressiveness (Aoki et al, 2003;Sato et al, 2003;Shimamura et al, 2003Shimamura et al, , 2004Nakanishi et al, 2004;Shimada et al, 2004a, b;Wu et al, 2004;Nishizawa et al, 2005). There are no reports on the expression of dysadherin in testicular neoplasms.…”

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Involvement of dysadherin and E-cadherin in the development of testicular tumours

et al. 2005

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Testicular neoplasms are comprised of a variety of histologically different forms, and their pathogenesis has not been elucidated. Dysadherin is a recently described cell membrane glycoprotein, which has an anticell -cell adhesion function and downregulates E-cadherin. In this study, we examined immunohistochemically the expression of E-cadherin and dysadherin in 120 testicular neoplasms (37 seminomas-26 classic, five spermatocytic and six anaplastic-, 45 embryonal carcinomas, 10 mixed germ cell tumours, two yolk sac tumours, 10 mature and eight immature teratomas and eight non-Hodgkin B-cell lymphomas), clinical stage I. The intensity, the expression pattern and the percentage of neoplastic cell staining was recorded and correlated with the histologic type and vascular/lymphatic invasion. Dysadherin was not expressed in non-neoplastic germ cells, neither in CIS/ITGCNU, but it was highly expressed in all types of germ cell tumours, that demonstrated either embryonic phenotype or somatic differentiation, in most terminally differentiated neoplasms, and in all lymphomas. Dysadherin expression did not correlate with vascular invasion. Increased dysadherin expression was correlated with aberrant E-cadherin expression in most tumours. In 17% of embryonal carcinomas colocalisation of dysadherin and membranous E-cadherin staining was noted. This is the first report on dysadherin expression and its association with E-cadherin in testicular tumours. Since dysadherin is not normally expressed in non-neoplastic testis, it is conceivable that it plays a role in the neoplastic transformation of germ cells. In testicular tumours, as in other neoplasms, dysadherin downregulates E-cadherin expression, at least in part.

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Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of the Stainingmentioning

confidence: 99%

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Involvement of dysadherin and E-cadherin in the development of testicular tumours

et al. 2005

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“…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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“…Therefore, identification of factors that accurately predict the prognosis is essential. Although adjuvant chemotherapy or radiation therapy is needed after resection, unfortunately they are insufficient to eliminate the cancer tissue completely and to distinguish it from surrounding healthy tissues (Aoki et al 2003;Salvador 2008). In this regard, it is essential to develop novel strategies and agents having improved pharmacologic profile and low toxicity without having drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells

2014

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Dysadherin is a recently found anti-adhesion molecule, therefore detection and down regulation of its expression is promising in cancer treatment. The up-regulation of dysadherin contributes to colon cancer recurrence and metastasis. Dysadherin also has connections with cytoskeletal proteins and it can cause alterations in the organisation of filamentous actin (Factin) in metastatic cancers. In this study, hypericin (HYP)-mediated photodynamic therapy (PDT) was performed in two different grade colon adenocarcinoma cell lines HT-29 (Grade I) and Caco-2 (Grade II). Cells were treated with 0.04, 0.08 or 0.15 lM HYP concentrations and irradiated with (4 J/cm 2 ) fluorescent lamps. The effects of HYP was examined 16 and 24 h after the activation. We investigated for the first time the effect of HYP-mediated PDT on the expression of dysadherin and F-actin organisation. According to the results, HYP mediated PDT caused a decrease in gene expression and immunofluorescence staining of dysadherin and an increase in actin stress fibers and actin aggregates in HT-29 and Caco-2 cell lines. Besides, cytotoxicity, number of floating cells and apoptotic index changed depending on the cell type, HYP concentration and incubation time. We have demonstrated for the first time that dysadherin and F-actin could be target molecules for HYP-

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Prognostic significance of dysadherin expression in advanced colorectal carcinoma

Cited by 47 publications

References 34 publications

Involvement of dysadherin and E-cadherin in the development of testicular tumours

Involvement of dysadherin and E-cadherin in the development of testicular tumours

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

Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells

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