Dysadherin Overexpression in Pancreatic Ductal Adenocarcinoma Reflects Tumor Aggressiveness: Relationship to E-Cadherin Expression

Shimamura, Takeshi; Sakamoto, Michiie; Ino, Yoshinori; Sato, Yasuto; Shimada, Kazuaki; Kosuge, Tomoo; Sekihara, Hisahiko; Hirohashi, Setsuo

doi:10.1200/jco.2003.06.179

Cited by 77 publications

(94 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2005

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2005

View full text Add to dashboard Cite

show abstract

“…It interacts with and modulates the properties of the Na þ , K þ ATPase (Ino et al, 2002;Lubarski et al, 2005). In human tissues increased dysadherin expression has been correlated with the development of metastasis and poor prognosis in gastric, pancreatic, colorectal, oesophageal, thyroid, tongue and cervical carcinomas, as well as in malignant melanoma (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;Batistatou et al, 2005Batistatou et al, , 2006Nishizawa et al, 2005;Kyzas et al, 2006). Furthermore, in a small pilot series of breast cancer patients, dysadherin expression was correlated with poor prognosis (Ino et al, 2002).…”

Section: Dysadherin In Breast Carcinomamentioning

confidence: 99%

“…Furthermore, in a small pilot series of breast cancer patients, dysadherin expression was correlated with poor prognosis (Ino et al, 2002). In most of these neoplasms, as well as in testicular tumours and lymph node metastases of colorectal adenocarcinoma, increased dysadherin expression was correlated with reduced E-cadherin expression (Aoki et al, 2003;Sato et al, 2003;Shimamura et al, 2003Shimamura et al, , 2004Wu et al, 2004;Batistatou et al, 2005Batistatou et al, , 2006. In invasive ductal carcinoma, as reported in this study, there is an increase in dysadherin expression, which is not related to E-cadherin expression.…”

Section: Dysadherin In Breast Carcinomamentioning

confidence: 99%

“…This novel cancer-associated protein has been detected in head and neck, tongue, oesophageal, gastric, colorectal, testicular, pancreatic, thyroid, and cervical carcinomas as well as in malignant melanoma and has been associated with tumour aggressiveness (Ino et al, 2002;Tsuiji et al, 2002;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;Batistatou et al, 2005;Nishizawa et al, 2005;Batistatou et al, 2006;Kyzas et al, 2006). A recent in vitro study has demonstrated that dysadherin has prometastatic effects that are independent of E-cadherin expression (Nam et al, 2006).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2007

View full text Add to dashboard Cite

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

show abstract

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Ansari

Rosendahl

Elebro

et al. 2011

British Journal of Surgery

View full text Add to dashboard Cite

None of the molecular markers described can be recommended for routine clinical use as they were identified in small cohorts and there were inconsistencies between studies. Their prognostic and predictive values need to be validated further in prospective multicentre studies in larger patient populations. A panel of molecular markers may become useful in predicting individual patient outcome and directing novel types of intervention.

show abstract

Dysadherin Overexpression in Pancreatic Ductal Adenocarcinoma Reflects Tumor Aggressiveness: Relationship to E-Cadherin Expression

Abstract: In pancreatic ductal adenocarcinoma, dysadherin expression seems to reflect tumor aggressiveness and to be a positive marker of poor prognosis when considered both alone and in combination with downregulation of E-cadherin.

Cited by 77 publications

References 27 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

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

Systematic review of immunohistochemical biomarkers to identify prognostic subgroups of patients with pancreatic cancer

Contact Info

Product

Resources

About