E‐cadherin quantititive immunocytochemical assays in breast carcinomas

Charpin, Colette; García, Stéphane; Bouvier, Corinne; Devictor, B; Andrac, L; Choux, R; Lavaut, Marie‐Noëlle

doi:10.1002/(sici)1096-9896(199703)181:3<294::aid-path772>3.3.co;2-m

Cited by 27 publications

(48 citation statements)

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“…Among the carcinomas, 35% showed markedly reduced or absent E-cadherin expression, and this frequency is in agreement with other studies (47,48). Significantly, we noted a higher rate of E-cadherin down-regulation in high-grade carcinomas, confirming previous reports (46,51).…”

Section: Discussionsupporting

confidence: 93%

Aberrant Expression of Novel and Previously Described Cell Membrane Markers in Human Breast Cancer Cell Lines and Tumors

Huang¹,

Groth²,

Sossey‐Alaoui

et al. 2005

Clinical Cancer Research

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Purpose: In a previous gene expression array study, we identified some 300 genes that were differentially expressed in human epidermal growth factor receptor tyrosine kinase 2 (HER2)p ositive versus HER2-negative breast cancer cells.We have now done validation experiments on a group of three cell membrane components that had previously not been implicated in breast cancer.We also studied the expression of three other cell membrane proteins known to play a role in mammary neoplasia. Experimental Design: By immunohistochemistry, we examined up to 130 archival breast carcinomas for Celsr2, E-cadherin, Kai1, and CD9 expression. The expression levels of NET-6 and TROP-2 were determined by quantitative reverse transcription-PCR in a subset of frozen tumors. We also studied fresh pellets and paraffin-embedded cell buttons of nine human breast cell lines. The relationship between the expression of all six membrane proteins and a variety of pathologic and biological variables, including estrogen receptor, HER2, and epidermal growth factor receptor status, was also examined. The NET-6 gene was transfected into a low-expressing cell line, and the effect on cellular morphology, growth, and invasion in vitro was recorded. Results: Celsr2 was down-regulated in one cell line and in 7% of breast cancers. E-cadherin, Kai1, and CD9 were down-regulated in 35%, 76%, and 79% of tumors, respectively, confirming the important role of these markers in human mammary neoplasia. In breast cancer cell lines and tissues, TROP-2 was generally expressed at low levels, although a few specimens showed relative overexpression. NET-6 levels were lower in HER2-negative breast carcinoma cells. In addition, NET-6 was markedly down-regulated in estrogen receptor^negative breast cancers, and expression was lowest in ''basal-like'' tumors. Ectopic expression of NET-6 in low-expressing MDA-MB-231cells altered cellular morphology, inhibited growth in vitro, and decreased invasion in a Boyden chamber assay. Conclusions: We have confirmed the expression of three new membrane markers that had previously not been implicated in human breast cancer, and one of them (NET-6) was correlated with HER2 and estrogen receptor status. NET-6 levels were decreased in estrogen receptor^negative and high-grade tumors, and ectopic expression of this gene had an inhibitory effect on proliferation and invasion. Thus, NET-6 may represent a novel breast cancer suppressor gene.

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Section: Discussionsupporting

confidence: 93%

Aberrant Expression of Novel and Previously Described Cell Membrane Markers in Human Breast Cancer Cell Lines and Tumors

Huang¹,

Groth²,

Sossey‐Alaoui

et al. 2005

Clinical Cancer Research

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“…This normal Down-regulation of E-cad, ␣-catenin, and ␤-catenin has been noted in a number of tumors and has been shown to be associated with high grade, high stage, and rapid progression in a number of tumors. [18][19][20][21][22][23][24][25][26] For example, Charpin et al 21 reported that down-regulation of E-cad expression was noted in a majority of breast carcinomas; this significantly correlated with tumor grade and expression of p53, MIB-1 (growth fraction) and c-erbB2 in breast carcinomas. In the liver, Ihara et al 29 reported that thin trabecular and pseudoglandular HCC preserved or overexpressed E-cad, ␣-catenin, and ␤-catenin, whereas thick trabecular HCC frequently showed low E-cad, ␣-catenin, and ␤-catenin expression.…”

Section: Discussionmentioning

confidence: 99%

Expression of e-cadherin, α-catenin, β-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

et al. 1998

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Immunolocalization of E-cadherin (E-cad), ␣-catenin, ␤-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, ␣-catenin, ␤-catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, ␣-catenin and ␤-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, ␣-catenin, and ␤-catenin was the same or reduced when compared with noncancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, ␣-catenin, and ␤-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for ␤-catenin, the down-regulation of which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 were frequently expressed at the membrane of CC cells. There were, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, ␣-catenin, and ␤-catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that ␤-catenin down-regulation is associated with c-erbB2 down-regulation. The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and CD44v5. (HEPATOLOGY 1998;27:974-982.)

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“…E-cadherin is a cellcell adhesion protein and it is extremely important in epithelial differentiation. E-cadherin expression and function has been extensively studied regarding its role in tumorigenesis and it is considered a powerful suppressor of mammary tumor invasions (Takeish 1991, Gamallo et al 1993, Pignatelli 1993, Lipponen et al 1994, Guriec et al 1996, Siitonen et al 1996, Charpin et al 1997, Zschiesche et al 1997, Asgeirsson et al 2000, Heimann et al 2000, Berx & Roy 2001, Reis-Filho et al 2002, Kowalsky et al 2003, Oesterreich et al 2003, Matos et al 2006. The e-cadherin gene is located in region 16q22.1 of the human chromosome, which is frequently affected by low heterozygosis in sporadic mammary neoplasms (Berx & Roy 2001, Oesterreich et al 2003.…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between E-cadherin expression and histological grade (Gamallo et al 1993, Guriec et al 1996, Siitonen et al 1996, Zschiesche et al 1996, Charpin et al 1997, histological type (Gamallo et al 1993, Guriec et al 1996, Zschiesche et al 1996, Charpin et al 1997, Matos et al 2006, hormonal receptors (Siitonen et al 1996, Charpin et al 1997, Gillett et al 2001, presence of metastasis in lymph nodes (Zschiesche et al 1996, Matos et al 2006, Siitonen et al 2006, necrosis (Matos et al 2006), survival rate (Guriec et al 1996, Zschiesche et al 1997, Asgeirsson et al 2000, Pedersen et al 2002, Brunetti et al 2005) and time free from metastasis (Pedersen et al 2002, Brunetti et al 2005), P53 and cerbB-2 expression (Charpin et al 1997) has been reported; there was also an association between low e-cadherin expression and the type of tumor differentiation (Restucci et al 1997, Reis et al 2003, but there was no significant association with hormonal receptors (Guriec et al 1996, Kovacs et al 2003, c-erbB-2 expression (Zschiesche et al 1997), lymph node involvement (Kovacs et al 2003), or clinical factors such as age, menopause and tumor size (Guriec et al 1996, Kovacs et al 2003.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical evaluation of e-cadherin, Ki-67 and PCNA in canine mammary neoplasias: correlation of prognostic factors and clinical outcome

et al. 2008

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RESUMO.-[Avaliação imuno-histoquímica da e-caderina, Ki-67 e PCNA nas neoplasias mamárias caninas: correlação dos fatores prognósticos com a evolução clínica.] A e-caderina é uma molécula de adesão celular e a perda de sua expressão esta relacionada à invasão tumoral podendo indicar um prognóstico ruim nas neoplasias mamárias. A expressão dos marcadores de proliferação celular PCNA e especialmente o Ki-67, também têm mostrado forte valor prognóstico nesta classe tumoral. A expressão imuno-histoquímica destes marcadores foi relacionada com as características clinico-patológicas de 73 tumores removidos cirurgicamente de fêmeas caninas. Não houve correlação estatística entre estes marcadores E-cadherin is a cell-cell adhesion molecule and low e-cadherin expression is related to invasiveness and may indicate a bad prognosis in mammary neoplasms. The expression of cell proliferation markers PCNA and especially Ki-67, has also proved to have a strong prognostic value in this tumor class. The expression of these markers was related to the clinical-pathological characteristics of 73 surgically removed mammary tumors in female dogs by immunohistochemistry. There was no statistical correlation between these markers and death by neoplasm, survival time and disease-free interval. However, the loss of e-cadherin expression and marked Ki-67 expression (p=0.016) were considered statistically significant for the diagnosis (p=0.032). When evaluated as independent factors, there was evidence of the relationship between the loss of e-cadherin expression and high PCNA expression with changes in the body status (divided into obese, normal and cachectic) of female dogs (p=0.030); there was also evidence of the relationship between pseudopregnancy and e-cadherin alone (p=0.021) and for ulceration and PCNA alone (p=0.035). The significant correlation between the markers expression and these well known prognostic factors used individually or in combination suggests their prognostic value in canine mammary tumors.INDEX TERMS: Canine, cell proliferation marker, e-cadherin, immunohistochemistry, mammary neoplasm.Pesq. Vet. Bras. 28(4):207-215, abril 2008 Debora A.P.C. Zuccari et al. 208 e a morte por neoplasia, tempo de sobrevida e intervalo livre de doença. Entretanto, a perda da expressão da ecaderina e a forte expressão do 016) foram considerados estatisticamente significativos quando relacionados com o diagnóstico (p=0,032). Quando avaliados os fatores independentes, houve evidência de associação entre a perda de expressão da e-caderina e a alta expressão do PCNA com as mudanças no estado nutricional das cadelas (divididas em obesas, normais e caquéticas) (p=0,030); houve também evidência de associação entre a pseudociese e a expressão da e-caderina (p=0,021) e com a ulceração e a expressão do PCNA (p=0,035). A correlação significativa entre a expressão dos marcadores e estes, bem conhecidos fatores prognósticos usados individualmente ou em associação, sugere importante valor prognóstico destes marcadores nos tumores mamários cani...

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E‐cadherin quantititive immunocytochemical assays in breast carcinomas

Cited by 27 publications

References 0 publications

Aberrant Expression of Novel and Previously Described Cell Membrane Markers in Human Breast Cancer Cell Lines and Tumors

Aberrant Expression of Novel and Previously Described Cell Membrane Markers in Human Breast Cancer Cell Lines and Tumors

Expression of e-cadherin, α-catenin, β-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

Immunohistochemical evaluation of e-cadherin, Ki-67 and PCNA in canine mammary neoplasias: correlation of prognostic factors and clinical outcome

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