E-Cadherin Reactivity of 95 Noninvasive Ductal and Lobular Lesions of the Breast

Goldstein, Neal S.; Bassi, Deepa; Watts, John; Layfield, Lester J.; Yaziji, Hadi; Gown, Allen M.

doi:10.1309/b0dd-4m7h-gjg1-7kcw

Cited by 71 publications

(37 citation statements)

References 34 publications

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“…In cases with non-specific morphologic characteristics, categorization can be performed through IHC, and E-cadherin is currently used to differentiate between the two. The majority of ductal carcinomas express cytoplasmic E-cadherin, whereas most lobular carcinomas lack expression of E-cadherin [3,15,16] . In addition, the differences in CKs expression may be used: highmolecular-weight CK (clone 34βE12) is usually expressed by lobular carcinomas, but is absent or expressed at low levels in most cases of DCIS [3,17,18] .…”

Section: Lobular or Ductal Carcinoma: E-cadherin Ck8mentioning

confidence: 99%

Significance of immunohistochemistry in breast cancer

Zaha

2014

WJCO

205

129

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The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with (breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice.

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Section: Lobular or Ductal Carcinoma: E-cadherin Ck8mentioning

confidence: 99%

Significance of immunohistochemistry in breast cancer

Zaha

2014

WJCO

205

129

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“…48 In addition, although E-cadherin is very useful as an adjunct in differentiating ductal from lobular lesions, morphologically unequivocal cases of LCIS and invasive lobular carcinoma have been shown to demonstrate focal E-cadherin positivity. 49,50 Dabbs et al 51,52 recently reported the utility of p120-catenin in both classic and pleomorphic variants of LCIS. Characteristically, this antibody is diffusely localized to the cytoplasm in cases of lobular neoplasia, whereas in ductal lesions it remains localized to the membrane.…”

Section: Immunophenotypementioning

confidence: 99%

Lobular neoplasia: morphology, biological potential and management in core biopsies

O’Malley

2010

Modern Pathology

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Lobular neoplasia has been traditionally recognized as a marker of increased risk for subsequent breast carcinoma development; however, molecular studies suggest that it also behaves in a non-obligate precursor manner. We do not know, as yet, how to identify the subgroup of cases that is most likely to progress, but the epidemiological data would indicate that this progression occurs after a long period of time. Thus, the current approach of conservative management of these lesions when identified in excision specimens is justified. Recently, several variants of lobular carcinoma in situ (LCIS), most notably pleomorphic LCIS, have been recognized and these can be difficult to differentiate from ductal carcinoma in situ. Application of strict diagnostic criteria and the judicial use of immunohistochemistry, particularly E-cadherin, can be helpful in this differential diagnosis. Another challenging issue is the management of lobular neoplasia when diagnosed on core biopsy. This controversial issue will be discussed in detail. The goals of this review are (1) to describe the morphological criteria used to diagnose the spectrum of lobular neoplastic lesions, including atypical lobular hyperplasia, LCIS and variants of LCIS; (2) to discuss the data exploring the biological potential of lobular neoplasia from an epidemiological and molecular viewpoint; and (3) to outline the recommendations for management of lobular neoplasia when encountered in core biopsies.

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“…Reduced expression of E-cadherin has been reported in invasive ductal carcinoma whereas lobular carcinoma in situ and invasive lobular carcinoma show complete loss of the protein. [6][7][8][9][10][11][12][13][14][15][16] A report on invasive lobular carcinomas with adjacent lobular carcinoma in situ demonstrated not only loss of Ecadherin expression but also the simultaneous loss of beta-, gamma-and alpha-catenin protein expression. 15 More recently, Sarrio et al 17 demonstrated that the loss of E-cadherin along with the cytoplasmic localization of p120-catenin characterizes lobular breast cancers and suggested that p120-catenin plays a role in mediating the oncogenic effects of Ecadherin loss in these cancers.…”

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confidence: 99%

E-cadherin alterations in atypical lobular hyperplasia and lobular carcinoma in situ of the breast

et al. 2005

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Tumor development from an early lesion through to invasive disease is not a clearly defined progression in the breast. Studies of invasive lobular carcinoma have reported mutations, loss of heterozygosity (LOH) and loss of protein expression in epithelial (E)-cadherin, a protein involved in cell adhesion. Our study examines in situ lobular neoplastic lesions without concurrent invasive carcinoma for E-cadherin gene alterations and protein expression, beta-catenin, alpha-catenin and p120-catenin protein expression, and LOH at the chromosome 16q locus, with the goal of determining the events occurring at the stage of lobular neoplasia. In all, 13 atypical lobular hyperplasia lesions and 13 lobular carcinoma in situ lesions from archived cases were examined. E-cadherin sequence alterations were evaluated using single strand conformation polymorphism and DNA sequencing, and PCR-based LOH analysis was carried out for the 16q locus. Using immunohistochemistry, we assessed protein expression. A total of 23 of 24 lesions evaluated by immunohistochemistry were negative for both E-cadherin and beta-catenin protein expression, and 21 of 23 lesions were negative for alpha-catenin. Cytoplasmic (rather than membrane) localization of p120-catenin was observed in 20 of 21 cases. Lobular carcinoma in situ cases were characterized by mutations; however, atypical lobular hyperplasia cases were not. LOH at 16q was an infrequent event. From our study, we conclude that an altered E-cadherin adhesion complex is an early event affecting atypical lobular hyperplasia as well as lobular carcinoma in situ and occurs prior to progression to invasive disease. However, the loss of protein expression is accompanied by E-cadherin DNA alterations in lobular carcinoma in situ but not in atypical lobular hyperplasia. These cases lacking both protein expression and gene alterations suggest that another mechanism is involved, possibly as early as at the hyperplastic stage, causing silencing of the E-cadherin complex.

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E-Cadherin Reactivity of 95 Noninvasive Ductal and Lobular Lesions of the Breast

Cited by 71 publications

References 34 publications

Significance of immunohistochemistry in breast cancer

Significance of immunohistochemistry in breast cancer

Lobular neoplasia: morphology, biological potential and management in core biopsies

E-cadherin alterations in atypical lobular hyperplasia and lobular carcinoma in situ of the breast

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