Clinical and Biological Significance of E-cadherin Protein Expression in Invasive Lobular Carcinoma of the Breast

Rakha, Emad A.; Patel, Arjun; Powe, Des G.; Benhasouna, Ahmed; Green, Andrew; Lambros, Maryou B.; Reis‐Filho, Jorge S.; Ellis, Ian O.

doi:10.1097/pas.0b013e3181f01916

Cited by 130 publications

(102 citation statements)

References 50 publications

(95 reference statements)

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“…We did not base it on E-cadherin expression as there is good evidence that about 10-15% of invasive lobular carcinomas show some membranous expression. 2,31 Indeed it is possible for an invasive lobular carcinoma with a typical morphology to have an E-cadherin mutation, but show E-cadherin expression. 31 Also, some nonlobular carcinomas lack E-cadherin expression.…”

Section: Discussionmentioning

confidence: 99%

“…Some of the tumours were stained as part of a previous study. 2 Hormonal therapy was given to 107 patients and chemotherapy to 34 patients. None of the patients received adjuvant trastuzumab therapy.…”

Section: Clinicopathological Featuresmentioning

confidence: 99%

“…It comprises several histological subtypes, all characterised by dyscohesive growth pattern and loss of function of the cell-adhesion protein E-cadherin. [1][2][3][4][5] Pleomorphic lobular carcinoma was first described in 1987 by Page 6 as a variant of classical invasive lobular carcinoma. It is characterised by a classical growth pattern, but has marked nuclear atypia and frequently shows a plasmacytoid, histiocytoid or apocrine morphological appearance.…”

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confidence: 99%

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Pleomorphic lobular carcinoma of the breast: is it a prognostically significant pathological subtype independent of histological grade?

et al. 2013

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Pleomorphic lobular carcinoma is regarded as a biologically aggressive variant of invasive lobular carcinoma of the breast. However, there is no consensus on the definition and whether this subtype adds useful information to histological grade. Two-hundred and two grade 2 or grade 3 invasive lobular carcinomas were studied. Tumours were categorised according to the components of histological grade: tubules, pleomorphism and mitoses. Pleomorphic lobular carcinoma was defined as a carcinoma with a lobular growth pattern and marked nuclear pleomorphism (pleomorphism 3). Breast cancer-specific survival was used in analysis of prognosis. Grade 3 pleomorphic lobular carcinomas (tubules 3, pleomorphism 3, mitoses 2 and tubules 3, pleomorphism 3, mitoses 3) had a worse prognosis than grade 2 (tubules 3, pleomorphism 2, mitoses 1) carcinomas. Grade 2 lobular carcinomas with marked nuclear pleomorphism (tubules 3, pleomorphism 3, mitoses 1) had a similar prognosis to grade 2 carcinomas with moderate pleomorphism (tubules 3, pleomorphism 2, mitoses 1). Survival was associated with mitotic score, but not with nuclear pleomorphism on both univariate and multivariate analysis. A non-classical growth pattern was seen more frequently in all subgroups with marked nuclear pleomorphism and was associated with worse survival. Histological grade and nodal status were independent of prognostic factors. This study shows that histological grade (in particular the mitotic component) in invasive lobular carcinomas is of prognostic importance, but pleomorphic type does not provide useful additional prognostic information.

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Section: Discussionmentioning

confidence: 99%

Section: Clinicopathological Featuresmentioning

confidence: 99%

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Pleomorphic lobular carcinoma of the breast: is it a prognostically significant pathological subtype independent of histological grade?

et al. 2013

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“…Loss of b-catenin has been described in human invasive lobular carcinomas. 30 Indeed, the association observed between the combined preservation of E-cad/b-cat and metastasis was stronger than in each of the individual biomarkers, suggesting that this variable would be a better prognostic factor that the study of E-cadherin preservation alone.…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of E-cadherin and β-catenin and High Expression of Basal Cytokeratins in Feline Mammary Carcinomas With Regional Metastasis

et al. 2012

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Feline mammary carcinomas are highly aggressive neoplasms. Several mechanisms are thought to be involved in their progression, including the loss of epithelial adhesion molecules. The present study was carried out on 21 adenomas and 139 mammary carcinomas. Of the carcinomas, 66 were not reported to have metastasized, while the remaining 73 had evidence of regional lymph node metastasis at the moment of diagnosis. The relationship was examined between the expression of the E-cadherin-b-catenin complex and basal (CK5/6, CK14) and luminal (CK8/18) cytokeratin expression. In the medical literature, carcinomas expressing basal cytokeratins are reported as having a poor prognosis in human breast cancer. Results revealed that preservation of the expression of E-cadherin and b-catenin is a significant feature of carcinomas without metastasis, whereas carcinomas with metastasis reveal the loss of one or both adhesion molecules. Additionally, basal cytokeratin expression was statistically associated with the presence of regional metastasis. Furthermore, the expression of E-cadherin-b-catenin was significantly correlated with the high expression of CK18 and low expression of CK5/6. Keywords feline mammary carcinoma, immunohistochemistry, E-cadherin, b-catenin, basal cytokeratinsMammary neoplasia is the third-most-common tumor type affecting female cats, following hemopoietic neoplasms and skin tumors. Malignancy is frequently reported and presents with local and distant metastases and high mortality rates. 42 Based on age, incidence, risk factors, histopathology, prognostic aspects, metastatic pattern, and response to therapy, feline mammary carcinomas have been proposed as a good model for human breast cancer. 2,42 Similar to reports in women, many veterinary studies describe regional lymph node involvement as one of the most important prognostic factors for feline mammary tumors. 11,16

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“…However, despite lack of FDA approval, there are many IHC markers utilized in some clinics to assist pathologists in diagnosis and decision making. Such examples include the use of E‐Cadherin and/or p120 staining to assist diagnosis of invasive lobular breast carcinoma (Rakha et al., 2010), various antibody panels for diagnosis and sub‐classification of malignant lymphomas, as well as the use of the proliferating nuclear marker, Ki67.…”

Section: Review Of Clinically Used Ihc Markers Approved By Fdamentioning

confidence: 99%

Garbage in, garbage out: A critical evaluation of strategies used for validation of immunohistochemical biomarkers

et al. 2014

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The use of immunohistochemistry (IHC) in clinical cohorts is of paramount importance in determining the utility of a biomarker in clinical practice. A major bottleneck in translating a biomarker from bench‐to‐bedside is the lack of well characterized, specific antibodies suitable for IHC. Despite the widespread use of IHC as a biomarker validation tool, no universally accepted standardization guidelines have been developed to determine the applicability of particular antibodies for IHC prior to its use. In this review, we discuss the technical challenges faced by the use of immunohistochemical biomarkers and rigorously explore classical and emerging antibody validation technologies. Based on our review of these technologies, we provide strict criteria for the pragmatic validation of antibodies for use in immunohistochemical assays.

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Clinical and Biological Significance of E-cadherin Protein Expression in Invasive Lobular Carcinoma of the Breast

Cited by 130 publications

References 50 publications

Pleomorphic lobular carcinoma of the breast: is it a prognostically significant pathological subtype independent of histological grade?

Pleomorphic lobular carcinoma of the breast: is it a prognostically significant pathological subtype independent of histological grade?

Reduced Expression of E-cadherin and β-catenin and High Expression of Basal Cytokeratins in Feline Mammary Carcinomas With Regional Metastasis

Garbage in, garbage out: A critical evaluation of strategies used for validation of immunohistochemical biomarkers

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