Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

This article has been updated

Abstract

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 post-transcriptional 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.

Main

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 al, 1994; Hirohashi, 1998; Chang et al, 2002; Charalabopoulos et al, 2002, 2004; Hirohashi and Kanai, 2003; Mastracci et al, 2005; Massarelli et al, 2005). In the vast majority of these neoplasms such expression has been associated with poor differentiation, increased metastatic potential and poor prognosis. In breast the scenario is more complicated, since lobular carcinoma, that typically does not express E-cadherin has a more favourable outcome than ductal carcinoma, which in general expresses E-cadherin. Furthermore, there are contradictory data on the possible association between E-cadherin expression and high-grade tumours with increased metastatic potential (Oka et al, 1993; Charpin et al, 1997; Heimann et al, 2000; Gillett et al, 2001; Parker et al, 2001; Elzagheid et al, 2002; Gupta et al, 2003; Knudsen and Wheelock, 2005; Rakha et al, 2005). It is clear that there are pieces missing from the puzzle of adhesion molecules and breast carcinoma.

Recently, the cloning and characterisation of dysadherin (FXYD5), a cell membrane glycoprotein that has an anti-cell–cell adhesion function and downregulates E-cadherin in a post-transcriptional manner has been reported, by members of our research team. 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, 2003, 2004; Nakanishi et al, 2004; Shimada et al, 2004a, 2004b; 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). The aim of the present study was to investigate further the expression of dysadherin in breast carcinoma, with particular emphasis to the acquisition of a lobular or a ductal phenotype, in combination with E-cadherin expression.

Materials and methods

One hundred formalin-fixed, paraffin-embedded archival tissue blocks of breast carcinomas were included in the current study and represented an equal number of female patients (mean age 54.5 years, range 35–79). The material consisted of 70 invasive ductal carcinomas, no special type, NST (10 Grade 1, 45 Grade 2 and 15 Grade 3, graded using the modified Bloom and Richardson method), in 30 of which an adjacent in situ ductal carcinoma was identified, and 30 invasive lobular carcinomas, in 15 of which an adjacent in situ lobular carcinoma was identified.

Immunohistochemistry

We performed immunostaining on formalin-fixed, paraffin-embedded tissue sections using the EnVision System (DAKO Corp., Netherlands), and the monoclonal antibodies: NCC-M53 against dysadherin and E-cadherin (CM170B, Biocare Medical, CA, USA). Briefly, 4-μm-thick tissue sections were deparaffinised in xylene; rehydrated through graded concentrations of alcohol and heated in a microwave oven for two cycles of 15 min each at 300 W, in citrate buffer, for antigen retrieval. Endogenous peroxidase activity was blocked with H2O2 solution in methanol (0.01 M), for 30 min. After washing with phosphate-buffered saline (PBS) for 5 min, the primary antibodies NCC-M53 (dilution 1 : 1000) and CM170B (dilution 1 : 50) were applied for incubation (30 min at room temperature and overnight at 4°C respectively). Then the slides were washed for 10 min with PBS and were visualised with the EnVision system using diaminobezidine tetrahydrochloride as a chromogen. Finally, all sections were counterstained with haematoxylin. Positive staining of endothelial cells and lymphocytes was used as an internal positive control for dysadherin. As an internal positive control for E-cadherin, positive staining of non neoplastic ductal epithelial cells was used. As a negative control the first antibody was substituted with normal mouse immunoglobulin of the same class.

Evaluation of the staining

For each sample, at least 1000 neoplastic cells were counted, and the percentage of cancer cells with positive membranous immunostaining as well as the staining intensity were recorded. 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(+))’. When less than 50% of tumour cells were stained for dysadherin, the tumour was evaluated as ‘negative dysadherin expression (Dys(−))’. Regarding E-cadherin, when more than 50% of tumour cells showed complete membranous staining, the tumour was evaluated as ‘preserved E-cadherin expression (E-cad(+))’, while when less than 50% of tumour cells were positive, the tumour was evaluated as ‘reduced E-cadherin expression (E-cad(−))’. Cytoplasmic immunostaining was considered as aberrant expression and was not included in the immunopositive cases.

Statistical analysis

Analyses were conducted in SPSS software version 11.0 (SPSS, Inc, Chicago, IL, USA). For comparisons between antibodies’ expression with clinicopathological variables we used the χ2 test. The level of statistical significance was P<0.05.

Results

Ductal carcinoma

Membranous E-cadherin expression was detected in epithelial cells of non-neoplastic ducts and acini and this served as internal positive control. In neoplastic cells there was some variation in distribution, depending on the grade and the pattern of stroma infiltration. Specifically, all 10 (100%) Grade 1, 37 out of 45 (82.2%) Grade 2 and six out of 15 (40%) Grade 3 neoplasms showed preserved E-cadherin expression (Table 1, Figure 1A). In immunopositive Grade 2 and Grade 3 tumours the expression of E-cadherin was more heterogeneous, with variations in intensity and distribution of positive cells. Thus, cells in clusters or in tubular structures exhibited higher percentage and more intense membranous staining than individual cells infiltrating the stroma. In the periphery of the invasive ductal carcinoma an intraductal component was observed in several cases. In this in situ ductal component the expression of E-cadherin was similar to the non-neoplastic epithelial cells, homogeneous and stronger that the adjacent invasive component (Figure 1B).

Table 1 E-cadherin and dysadherin expression in invasive breast carcinomas
Figure 1
figure1

A case of invasive ductal carcinoma, grade II, with adjacent in situ component. (A) E-cadherin expression is significantly reduced in invasive ductal carcinoma (DABX400). (B) Membranous expression of E-cadherin is retained in the adjacent in situ component (DABX400). (C) Strong, membranous expression of dysadherin is evident in invasive ductal carcinoma (DABX400). (D) Dysadherin is not expressed in the adjacent in situ component (DABX400).

Dysadherin expression was detected in myoepithelial cells of ducts and acini, but not in non-neoplastic epithelial cells, as well as in endothelial cells of vessels and lymphocytes, as described previously (Batistatou et al, 2005, 2006). Dysadherin immunostaining was observed in the membranes of the neoplastic cells and it was heterogeneous throughout the neoplasm (Figure 1C). In particular, preferential expression in diffuse than in compact infiltrative areas was detected. Overall, ‘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 (Table 1, Figure 1B). Interestingly, in the adjacent in situ ductal carcinoma a small proportion of neoplastic cells (<10%) exhibited membranous immunostaining for dysadherin (Figure 1D). Dysadherin expression was not correlated with E-cadherin expression in IDC (P>0.05).

Lobular carcinoma

None of the 30 infiltrating lobular carcinomas showed preserved E-cadherin expression (Table 1, Figure 2A). The vast majority was completely negative, while only in two of them, <20% of neoplastic cells showed weak membranous and cytoplasmic immunopositivity. Interestingly, the adjacent in situ lobular carcinoma was completely negative, as well (Figure 2B).

Figure 2
figure2

A case of invasive lobular carcinoma, with adjacent in situ component. (A) E-cadherin expression is lost in invasive lobular carcinoma (DABX400). (B) E-cadherin expression is lost in the adjacent in situ component (DABX400). (C) Membranous expression of dysadherin is evident in invasive lobular carcinoma, (DABX400). (D) Dysadherin is not expressed in the adjacent in situ component, in contrast with the infiltrating tumour (DABX400).

All the 30 infiltrating lobular carcinomas exhibited ‘positive dysadherin expression’ (Figure 2C). In this in situ lobular component the expression of dysadherin was limited to a small proportion (<10%) of neoplastic cells (Figure 2D).

Discussion

Two of the most important characteristics of neoplastic cells are their abilities to grow locally and to metastasise. For both of these processes tumour cells must initially dissociate from each other, either singly or in small nests and invade the surrounding stroma. Today it is generally accepted that at least for carcinomas, adhesion molecules, in particular E-cadherin, play a pivotal role in this process by being downregulated (Hirohashi, 1998; Charalabopoulos et al, 2002; Hirohashi and Kanai, 2003). In general, there is an association between aberrant E-cadherin expression, tumour dedifferentiation and poor clinical outcome.

Regarding breast cancer, E-cadherin expression varies depending on the histological subtype. Thus, in ductal carcinoma E-cadherin is expressed, albeit in reduced levels and aberrant cellular locations. Although E-cadherin correlates inversely with the grade of the tumour, reduced E-cadherin expression is not adequate to predict clinical outcome and there are contradictory studies on the association between E-cadherin and survival (Knudsen and Wheelock, 2005). Moreover, it has been reported that in other breast cancers with known poor prognosis, such as inflammatory breast cancer, there is overexpression of E-cadherin (Knudsen and Wheelock, 2005). An interesting concept is that possibly the reduction of E-cadherin expression in breast carcinomas, other than lobular, is transient, due to epigenetic modifications. Several mechanisms for reversible reduction of E-cadherin expression in human neoplasms have been reported (Hirohashi, 1998; Charalabopoulos et al, 2002; Hirohashi and Kanai, 2003). Among them, recently, a novel cell membrane glycoprotein named ‘dysadherin’ (from the Greek prothema dys-, which means difficulty, or aberration, or reversibility) has been shown to downregulate E-cadherin in a post-transcriptional manner and reduce cell–cell adhesiveness in in vitro studies and in animal models. Dysadherin is a member of the FXYD family (FXYD5 or Related to Ion Channel). It is located at chromosome 19 and has a single transmembrane domain. It interacts with and modulates the properties of the Na+, K+ 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, 2003, 2004; Nakanishi et al, 2004; Shimada et al, 2004a, 2004b; Wu et al, 2004; Batistatou et al, 2005, 2006; Nishizawa 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). 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, 2003, 2004; Wu et al, 2004; Batistatou et al, 2005, 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. 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. On the basis of these data we would like to propose that in ductal carcinomas, dysadherin can promote invasion independently of the E-cadherin expression.

Lobular breast carcinomas, typically exhibit loss of E-cadherin expression, but they tend to have a more favourable clinical outcome than the more common ductal carcinomas. This loss is an early event affecting not only lobular carcinoma in situ but even atypical lobular neoplasia (Mastracci et al, 2005). This silencing of E-cadherin is attributed to genetic as well as epigenetic events (Knudsen and Wheelock, 2005; Mastracci et al, 2005). In approximately 50% of lobular carcinomas loss of E-cadherin involves LOH at the chromosomal region of 16q, which includes the E-cadherin gene CDH1 locus and mutations in the remaining allele (Kanai et al, 1994; Vos et al, 1997; Huiping et al, 1999; Knudsen and Wheelock, 2005; Mastracci et al, 2005). This LOH definitely accompanies mutations in cases of invasive lobular carcinoma, however, the classic pattern of LOH coupled with inactivating mutations in lobular carcinoma in situ has not been confirmed. In the other 50% loss of E-cadherin is attributed to epigenetic events, with hypermethylation of the E-cadherin promoter region at CpG islands being one of the most important ones and possibly occurring very early, even at the stage of atypical lobular hyperplasia (Sarrio et al, 2004; Shibata et al, 2004; Knudsen and Wheelock, 2005; Mastracci et al, 2005).

In this study we have confirmed the loss of E-cadherin expression, in in situ and invasive breast carcinoma. On the basis of the rare expression of dysadherin in lobular carcinoma in situ we can conclude that dysadherin is not responsible for E-cadherin downregulation in lobular carcinoma. An interesting finding from our study is the difference in dysadherin expression between in situ and invasive lobular carcinoma. In breast carcinoma the progression from in situ to invasive disease is not clearly defined and the specific events that mark the transition to an invasive tumour are under intense investigation. Lack of E-cadherin expression cannot be associated with an invasive phenotype, since it is also evident in the in situ component. On the other hand, we have shown that dysadherin is specifically and constantly expressed in invasive lobular carcinomas. On the basis of this finding we propose that dysadherin is a possible causative player in the process of acquiring an invasive phenotype, as well as a possible marker for invasiveness. It has also been proposed that loss of E-cadherin expression is responsible for the distinct pattern of invasion observed in lobular neoplasms (Knudsen and Wheelock, 2005; Mastracci et al, 2005). We would like to add that another major contributor to this characteristic invasion pattern, with single cells arranged in cords is the expression of dysadherin. The latter possibly acts, either alone or in conjunction with loss of E-cadherin, by allowing cells to dissociate from each other. Studies on the function of dysadherin are available by experimental data, where dysadherin appears to play an important role in neoplastic cell invasion and metastasis (Ino et al, 2002; Nam et al, 2006). The exact molecular mechanisms of these effects have not been elucidated yet. Recently, it has been shown that, besides downregulating E-cadherin, dysadherin can promote invasion at least in breast cancer cells in vitro, through an E-cadherin-independent mechanism. This mechanism involves enhanced signaling through the NF-κB pathway, which leads to increased production of the tumour-promoting (C-C motif) ligand 2 (CCL2) (Nam et al, 2006).

In conclusion, in this study we have investigated the role of specific adhesion/dysadhesion molecules in the development of breast carcinoma. We have selected ductal carcinoma which is by far the most common type, and lobular carcinoma which has a distinctive microscopic appearance. We have shown similarities and differences between these two types. Interestingly, 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 E-cadherin. Thus, 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.

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  1. Aoki S, Shimamura T, Shibata T, Nakanishi Y, Moriya Y, Sato Y, Kitajima M, Sakamoto M, Hirohashi S (2003) Prognostic significance of dysadherin expression in advanced colorectal carcinoma. Br J Cancer 88: 726–732

    CAS  Article  Google Scholar 

  2. Batistatou A, Charalabopoulos AK, Scopa CD, Nakanishi Y, Kappas A, Hirohashi S, Agnantis NJ, Charalabopoulos K (2006) Expression patterns of dysadherin and E- cadherin in lymph node metastases of colorectal carcinoma. Virchows Arch 448: 763–777

    CAS  Article  Google Scholar 

  3. Batistatou A, Scopa CD, Ravazoula P, Nakanishi Y, Peschos D, Agnantis NJ, Hirohashi S, Charalabopoulos KA (2005) Involvement of dysadherin and E-cadherin in the development of testicular tumors. Br J Cancer 93: 1382–1387

    CAS  Article  Google Scholar 

  4. Becker KF, Atkinson MJ, Reich U, Becker I, Nekarda H, Siewert JR, Hofler H (1994) E- cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res 54: 3845–3852

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Chang HW, Chow V, Lam KY, Wei WI, Yuen A (2002) Loss of E-cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance. Cancer 94: 386–392

    CAS  Article  Google Scholar 

  6. Charalabopoulos K, Binolis J, Karkabounas S (2002) Adhesion molecules in carcinogenesis. Exp Oncol 24: 249–257

    CAS  Google Scholar 

  7. Charalabopoulos K, Gogali A, Kostoula OK, Constantopoulos H (2004) Cadherin superfamily of adhesion molecules in primary lung cancer. Exp Oncol 16: 256–260

    Google Scholar 

  8. Charpin C, Garcia S, Bouvier C, Devictor B, Andrac L, Choux R, Lavaut M (1997) E-cadherin quantitative immunocytochemical assays in breast carcinomas. J Pathol 431: 317–321

    Google Scholar 

  9. Elzagheid A, Kuopio T, Ilmen M, Collan Y (2002) Prognostication of invasive ductal breast cancer by quantification of E-cadherin immunostaining:the methodology and clinical relevance. Histopathology 41: 127–133

    CAS  Article  Google Scholar 

  10. Gillett CE, Miles DW, Ryder K, Skilton D, Liebman RD, Springall RJ, Barnes DM, Hanby AM (2001) Retention of the expression of E-cadherin and catenins is associated with shorter survival in grade III ductal carcinoma of the breast. J Pathol 193: 433–441

    CAS  Article  Google Scholar 

  11. Gupta A, Desphande CG, Badve S (2003) Role of E-cadherins in development of lymphatic tumor emboli. Cancer 97: 2341–2347

    Article  Google Scholar 

  12. Heimann R, Lan F, McBride R, Hellman S (2000) Separating favourable from unfavourable prognostic markers in breast cancer: the role of E-cadherin. Cancer Res 60: 298–304

    CAS  Google Scholar 

  13. Hirohashi S (1998) Inactivation of E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153: 333–339

    CAS  Article  Google Scholar 

  14. Hirohashi S, Kanai Y (2003) Cell adhesion system and human cancer morphogenesis. Cancer Sci 94: 575–581

    CAS  Article  Google Scholar 

  15. Huiping C, Sigurgeirsdottir JR, Jonasson JG, Eiriksdottir G, Johannsdottir JT, Egilsson V, Ingvarsson S (1999) Chromosome alterations and E-cadherin gene mutations in human lobular breast cancer. Br J Cancer 81: 1003–1010

    Article  Google Scholar 

  16. Ino Y, Gotoh M, Sakamoto M, Tsukagoshi K, Hirohashi S (2002) Dysadherin, a cancer-associated cell membrane glycoprotein, downregulates E-cadherin and promotes metastasis. Proc Natl Acad Sci USA 99: 365–370

    CAS  Article  Google Scholar 

  17. Kanai Y, Oda T, Tsuda H, Ochiai A, Hirohashi S (1994) Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast. Jpn J Cancer Res 85: 1035–1039

    CAS  Article  Google Scholar 

  18. Knudsen KA, Wheelock MJ (2005) Cadherins and the mammary gland. J Cel Biol 95: 488–496

    CAS  Google Scholar 

  19. Kyzas PA, Stefanou D, Batistatou A, Agnantis NJ, Nakanishi Y, Hirohashi S, Charalabopoulos K (2006) Dysadherin expression in head and neck squamous cell carcinoma: association with lymphangiogenesis and prognostic significance. Am J Surg Pathol 30: 185–193

    Article  Google Scholar 

  20. Lubarski I, Pihakaski-Maunshbach K, Karlish SJ, Maunsbach AB, Garty H (2005) Interaction with the Na,K-Atpase and tissue distribution of FXYD5 (related to ion channel). J Biol Chem 280: 37717–37724

    CAS  Article  Google Scholar 

  21. Massarelli E, Brown E, Tran NK, Liu DD, Izzo JG, Lee JJ, El-Naggar AK, Hong WK, Papadimitrakopoulou VA (2005) Loss of E-cadherin and p27 expression is associated with head and neck squamous tumorigenesis. Cancer 103: 952–959

    CAS  Article  Google Scholar 

  22. Mastracci TL, Tjan S, Bane AL, O'Malley FP, Andrulis IL (2005) E-cadherin alterations in atypical lobular hyperplasia and lobular carcinoma in situ of the breast. Mod Pathol 18: 741–751

    CAS  Article  Google Scholar 

  23. Nakanishi Y, Akimoto S, Sato Y, Kanai Y, Sakamoto M, Hirohashi S (2004) Prognostic significance of dysadherin expression in tongue cancer: immunohistochemical analysis of 91 cases. Appl Immunohistochem Mol Morphol 12: 323–328

    CAS  Article  Google Scholar 

  24. Nam J-S, Kang M-J, Suchar AM, Shimamura T, Kohn EA, Michalowska AM, Jordan VC, Hirohashi S, Wakefield LM (2006) Chemokine (C-C motif) ligand 2 mediates the prometastatic effect of dysadherin in human breast cancer cells. Cancer Res 66: 7176–7184

    CAS  Article  Google Scholar 

  25. Nishizawa A, Nakanishi Y, Yoshimura K, Sasajima Y, Yamazaki N, Yamamoto A, Hanada K, Kanai Y, Hirohashi S (2005) Clinicopathologic significance of dysadherin expression in cutaneous malignant melanoma. Cancer 103: 1693–1700

    CAS  Article  Google Scholar 

  26. Oka H, Shiozaki H, Kabayashi K, Inoue M, Tahara H, Kobayashi T, Takatsuka Y, Matsuyoshi N, Hirano S, Takeichi M (1993) Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res 53: 1696–1701

    CAS  Google Scholar 

  27. Parker C, Rampaul RS, Pinder SE, Bell JA, Wencyk PM, Blamey RW, Nicholson RI, Robertson JF (2001) E-cadherin as a prognostic indicator in primary breast cancer. Br J Cancer 85: 1958–1963

    CAS  Article  Google Scholar 

  28. Rakha EA, Abd El, Rehim D, Pinder SE, Lewis Sa, Ellis IO (2005) E-cadherin expression in invasive non-lobular carcinoma of the breast and its prognostic significance. Histopathology 46: 685–693

    CAS  Article  Google Scholar 

  29. Sarrio D, Perez-Mies B, Hardisson D, Moreno-Bueno G, Suarez A, Cano A, Martin-Perez J, Gamallo C, Palacios J (2004) Cytoplasmic localization of p120ctn and E_cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions. Oncogene 23: 3272–3283

    CAS  Article  Google Scholar 

  30. Sato H, Ino Y, Miura A, Abe Y, Sakai H, Ito K, Hirohashi S (2003) Dysadherin: expression and clinical significance in thyroid carcinoma. J Clin Endocrinol Metab 88: 4407–4412

    CAS  Article  Google Scholar 

  31. Shibata T, Kokubu A, Sekine S, Kanai Y, Hirohashi S (2004) Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin deficient breast cancer. Am J Pathol 164: 2269–2278

    CAS  Article  Google Scholar 

  32. Shimada Y, Hashimoto Y, Kan T, Kawamura J, Okumura T, Soma T, Kondo K, Teratani N, Watanabe G, Ino Y, Sakamoto M, Hirohashi S, Imamura M (2004a) Prognostic significance of dysadherin expression in esophageal squamous cell carcinoma. Oncology 67: 73–80

    CAS  Article  Google Scholar 

  33. Shimada Y, Yamasaki S, Hashimoto Y, Ito T, Kawamura J, Soma T, Ino Y, Nakanishi Y, Sakamoto M, Hirohashi S, Imamura M (2004b) Clinical significance of dysadherin expression in gastric cancer patients. Clin Cancer Res 10: 2818–2823

    CAS  Article  Google Scholar 

  34. Shimamura T, Sakamoto M, Ino Y, Sato Y, Shimada K, Kosuge T, Sekihara H, Hirohashi S (2003) Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness: relationship to E-cadherin expression. J Clin Oncol 21: 659–667

    CAS  Article  Google Scholar 

  35. Shimamura T, Yasuda J, Ino Y, Gotoh M, Tsuchiya A, Nakajima A, Sakamoto M, Kanai Y, Hirohashi S (2004) Dysadherin expression facilitates cell motility and metastatic potential of human pancreatic cancer cells. Cancer Res 64: 6989–6995

    CAS  Article  Google Scholar 

  36. Tsuiji H, Takasaki S, Sakamoto M, Irimura T, Hirohashi S (2002) Aberrant O-glycosylation inhibits stable expression of dysadherin, a carcinoma-associated antigen, and facilitates cell-cell adhesion. Glycobiology 13: 521–527

    Article  Google Scholar 

  37. Vos CB, Cleton-Jansen AM, Berx G, de Leeuw WJ, ter Haar NT, van Roy F, Cornelisse CJ, Peterse JL, van de Vijver MJ (1997) E-cadherin inactivation in lobular carcinoma in situ of the breast:an early event in tumorigenesis. Br J Cancer 76: 1131–1133

    CAS  Article  Google Scholar 

  38. Wu D, Qiao Y, Kristensen GB, Li S, Troen G, Holm R, Nesland JM, Suo Z (2004) Prognostic significance of dysadherin expression in cervical squamous cell carcinoma. Pathol Oncol Res 10: 212–218

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to A Batistatou.

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and Permissions

About this article

Cite this article

Batistatou, A., Peschos, D., Tsanou, H. et al. In breast carcinoma dysadherin expression is correlated with invasiveness but not with E-cadherin. Br J Cancer 96, 1404–1408 (2007). https://doi.org/10.1038/sj.bjc.6603743

Download citation

Keywords

  • dysadherin
  • E-cadherin
  • breast
  • ductal carcinoma
  • lobular carcinoma

Further reading

Search

Quick links