Differential Expression of Dysadherin in Papillary Thyroid Carcinoma and Microcarcinoma: Correlation with E-cadherin

Batistatou, Anna; Charalabopoulos, Konstantinos; Nakanishi, Yukihiro; Vagianos, Constantine; Hirohashi, Setsuo; Agnantis, Niki J.; Scopa, Chrissoula D.

doi:10.1007/s12022-008-9035-1

Cited by 18 publications

(17 citation statements)

References 38 publications

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“…These results are in accordance with those of previous studies investigating E-cadherin expression in PTCs of all stages (23)(24)(25)(26)(27). Certain studies demonstrated a correlation between the loss of E-cadherin expression and disease progression or poorer prognosis in PTC (27,29); however, the results of the present study did not verify the clinical significance of E-cadherin expression in PTMC.…”

Section: Discussionsupporting

confidence: 93%

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E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

Nakamura

Onoda

Noda

et al. 2013

Molecular and Clinical Oncology

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Abstract. Although papillary thyroid microcarcinoma (PTMC) has an excellent prognosis, certain cases exhibit aggressive clinical manifestations. In this study, we assessed the expression of E-cadherin and Ki-67 in primary PTMC tumors and metastatic lymph nodes, in order to investigate the mechanism underlying the mainly indolent but potentially malignant nature of PTMC. A total of 93 PTMC patients treated in our institute were included in this study. All primary tumors and 57 metastatic lymph nodes were immunohistochemically stained and a total of 73 tumors (78.5%) were positive for E-cadherin. E-cadherin expression was significantly less common at the invasive front (58.1%, P<0.01) compared to that at the center of the tumor. Tumors that had lost E-cadherin expression at the invasive front frequently presented with lymph node metastasis (70.6%). Small tumors (≤5 mm diameter) expressed E-cadherin significantly more frequently compared with larger tumors (P=0.04); however, no other particular characteristic was found to correlate with the status of E-cadherin expression in the primary tumors. E-cadherin expression was detected in 49 (86.0%) of the 57 metastatic foci and correlated significantly with the expression status at the invasive front of the tumor (P=0.02). The Ki-67 index was universally low and was not correlated with the clinicopathological characteristics or the E-cadherin expression of the tumors. These results suggested that cancer cells in the metastatic lymph nodes exhibit indolent characteristics, similar to those of the primary PTMC. However, the metastatic cancer cells may have already completed the process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET), suggesting an innate malignant potential. IntroductionAccording to the World Health Organization classification system for thyroid tumors, papillary thyroid microcarcinoma (PTMC) is defined as a papillary thyroid carcinoma (PTC) measuring ≤10 mm in its greatest dimension (1). The occurrence of PTMC is on the increase worldwide (2-4), along with the frequent application of neck ultrasonography (US) (5,6). PTMC is generally characterized by an indolent clinical course and has an excellent prognosis, with a disease-specific mortality of <0.5% (6). However, certain PTMC cases were found to be clinically aggressive (6,7). According to the observations of Sugitani et al (7), PTMC patients with bulky lymph node metastases or extrathyroidal invasion were at the highest risk for a cancer-specific fatal outcome. Those observations suggested that there is a group of PTMCs that have already acquired highly malignant potential. However, the basic mechanism underlying the development of aggressive characteristics in these tumors has not yet been identified.The reported risk factors for PTMC recurrence were shown to be male gender (8,9), extent of primary surgery (10), presence of lymph node metastases at initial diagnosis (3,(8)(9)(10)(11)(12), tumor multifocality (3,8,12) and capsular invasion (9,(11)(12)(13)(14...

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Section: Discussionsupporting

confidence: 93%

“…E-cadherin is a well-known cellular adhesion molecule in epithelial cells and is known to be lost during the process of EMT. E-cadherin expression is commonly observed in differentiated thyroid cancer (23)(24)(25)(26)(27) and loss of its expression was reported to be an independent prognostic factor for these tumors (27).…”

Section: Introductionmentioning

confidence: 99%

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

Nakamura

Onoda

Noda

et al. 2013

Molecular and Clinical Oncology

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“…On the other hand, Naito et al (2001) found that E-CAD expression was preserved significantly less often in papillary cancer with lymph node metastasis than in node-negative cases, but E-CAD expression did not correlate significantly with other clinical factors including tumor diameter, extracapsular tumor extension or histological differentiation [12]. These and our results are thus in contrast to those reported by Brabant, von Wasilewski, Scheumman, Walgenbach and Batistatou [8][9][10][11]31]. Brabant et al (1993) observed lower or undetectable E-CAD immunoreactivity in tumors presenting lymph node metastases, distant metastases or local recurrence [8].…”

Section: Discussioncontrasting

confidence: 97%

“…Scheumman et al (1995) and Walgenbach et al (1998) reported that reduced (below 30% in the study by Scheumman and < 20% -in Walgenbach's study) or negative E-CAD expression was associated with advanced T categories of the primary tumors and higher rates of lymph node involvement and distant metastasis [9,10]. Batistatou et al (2008) found that the reduction of E-CAD expression in papillary microcancers was smaller than in other papillary cancers [31]. Our data did not confirm those observations.…”

Section: Discussioncontrasting

confidence: 61%

E-cadherin expression is more associated with histopathological type of thyroid cancer than with the metastatic potential of tumors

Słowińska-Klencka

Sporny²,

Stasikowska-Kanicka³

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The aim of this study was to evaluate the relationship between abnormal expression of E-cadherin (E-CAD) and the extracapsular extension of tumors, lymph node involvement and the presence of metastasis in various types of thyroid cancers. Histopathological specimens of 35 benign thyroid lesions and 122 malignant tumors (papillary, follicular, poorly differentiated and undifferentiated cancers) were analyzed. E-CAD immunostaining intensity, its subcellular localization, homogeneity within lesion, and the relation of staining intensity between tumor and surrounding thyroid parenchyma were evaluated. The obtained results show that the variants of differentiated cancers with a poorer prognosis (i.e. tall cell and follicular variants of papillary cancer and widely invasive follicular cancers) present reduced intensity of E-CAD expression, its abnormal localization or heterogeneity of staining more frequently than classical papillary cancers and minimally invasive follicular cancers. However, the assessment of E-CAD expression does not allow the prediction of extrathyroidal growth of thyroid cancers.

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“…In many tumor tissues, the protein level of FXYD5 inversely correlates with the level of E-cadherin (Batistatou et al, 2008;Maehata et al, 2011;Mitselou et al, 2010;Ono et al, 2010;Shimada et al, 2004); however, whether this is a result of FXYD5-induced downregulation of E-cadherin is unknown. Overexpression of FXYD5 reduced the levels of E-cadherin in particular cell lines (Ino et al, 2002), but had no effect in others (Lubarski et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell–cell trans-dimerization of Na,K-ATPase β1 subunits

Tokhtaeva

Sun

Deiss-Yehiely

et al. 2016

Journal of Cell Science

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FXYD5 (also known as dysadherin), a regulatory subunit of the Na,K-ATPase, impairs intercellular adhesion by a poorly understood mechanism. Here, we determined whether FXYD5 disrupts the transdimerization of Na,K-ATPase molecules located in neighboring cells. Mutagenesis of the Na,K-ATPase β 1 subunit identified four conserved residues, including Y199, that are crucial for the intercellular Na,K-ATPase trans-dimerization and adhesion. Modulation of expression of FXYD5 or of the β 1 subunit with intact or mutated β 1 -β 1 binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the β 1 subunit. Immunodetection of the plasma membrane FXYD5 was prevented by the presence of O-glycans. Partial FXYD5 deglycosylation enabled antibody binding and showed that the protein level and the degree of O-glycosylation were greater in cancer than in normal cells. FXYD5-induced impairment of adhesion was abolished by both genetic and pharmacological inhibition of FXYD5 O-glycosylation. Therefore, the extracellular O-glycosylated domain of FXYD5 impairs adhesion by interfering with intercellular β 1 -β 1 interactions, suggesting that the ratio between FXYD5 and α 1 -β 1 heterodimer determines whether the Na,K-ATPase acts as a positive or negative regulator of intercellular adhesion.

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Differential Expression of Dysadherin in Papillary Thyroid Carcinoma and Microcarcinoma: Correlation with E-cadherin

Cited by 18 publications

References 38 publications

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

E-cadherin expression and cell proliferation in the primary tumor and metastatic lymph nodes of papillary thyroid microcarcinoma

E-cadherin expression is more associated with histopathological type of thyroid cancer than with the metastatic potential of tumors

The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell–cell trans-dimerization of Na,K-ATPase β1 subunits

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