Molecular and Morphologic Distinctions between Infiltrating Ductal and Lobular Carcinoma of the Breast

Yoder, Brian J.; Wilkinson, Edward J.; Massoll, Nicole A.

doi:10.1111/j.1524-4741.2007.00393.x

Cited by 68 publications

(68 citation statements)

References 92 publications

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“…Although treatment for stage-matched ductal versus lobular carcinomas is similar [9], several studies have shown that ILC is a distinct entity of breast cancer that differs from IDC not only in histological and clinical features [10,11] but also in the risk factors [12], genomic profiles [13], global transcription programs [14], immunophenotype [15] and response to systemic therapy [11,16,17]. Such studies suggest that lobular tumour development and progression may follow a distinct pathway from ductal tumours.…”

Section: Introductionmentioning

confidence: 99%

The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology

Rakha

Gill

El-Sayed

et al. 2008

Breast Cancer Res Treat

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Section: Introductionmentioning

confidence: 99%

The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology

Rakha

Gill

El-Sayed

et al. 2008

Breast Cancer Res Treat

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“…75 Most lobular carcinomas show no immunohistochemical reactivity for E-cadherin as a consequence of mutation and loss of heterozygosity of the E-cadherin gene, or methylation of the E-cadherin promoter 76,77 and E-cadherin immunostaining has been of value in the differential diagnosis of ductal and lobular carcinomas. 78 E-cadherin downregulation is a key molecular change occurring in epithelial mesenchymal transition, a process by which epithelial cells modulate their phenotype and acquire mesenchymal-like properties.…”

Section: G Turashvili Et Almentioning

confidence: 99%

P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer

Turashvili¹,

McKinney²,

Göktepe³

et al. 2011

Modern Pathology

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P-cadherin is a calcium-dependent cell-cell adhesion glycoprotein. P-cadherin expression is restricted to the myoepithelial cells in normal breast tissue, and aberrant staining has also been described in invasive tumors. Several small studies have reported P-cadherin as a marker of poor outcome in breast cancer patients but its prognostic significance in relation to other variables has not been established in a large series of breast cancers. A tissue microarray was constructed from 3992 cases of invasive breast carcinoma, and P-cadherin expression was evaluated using immunohistochemistry. Median follow-up was 12.5 years. The immunohistochemistry-based definitions of cancer subtypes were luminal, and basal (ERÀ/PRÀ/HER2À/CK5/6 þ or EGFR þ ). Clinical covariate and biomarker associations were assessed using contingency tables, and Pearson's v 2 or Fisher's exact test. Survival associations were assessed using Kaplan-Meier plots, logrank and Breslow tests, and Cox proportional hazards regression analysis. P-cadherin was expressed in 34.8% (1290/3710, 50% cut point) of cases. P-cadherin staining was strongly associated with HER2 þ and basal carcinoma subtypes (Po0.0005). P-cadherin-positive patients showed significantly poorer short-term (0-10 years) overall survival, disease-specific survival, distant relapse-free interval, and locoregional relapse-free interval in univariable models (Po0.05). In multivariable Cox models containing standard clinical covariates and cancer subtypes, P-cadherin did not show independent prognostic value. P-cadherin expression was positively associated with histological grade, chemotherapy, EGFR, CK5/6, p53, and HER2 expression (Po0.002), and negatively associated with age at diagnosis, ER, PR, and Bcl-2 expression (Po0.0005). This study shows the value of P-cadherin as a marker of poor prognosis. The large sample size of this series clarifies contradictory findings of many smaller studies. P-cadherin positivity is associated with high-grade tumor subtypes and well-established markers of poor prognosis, and may represent a promising antibody therapeutic target.

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“…Loss of E-cadherin protein expression is most frequent for infiltrating lobular tumor types and can occur by somatic or germline mutation or by loss of heterozygosity, indicating that E-cadherin acts as a classic tumor suppressor gene (Kanai et al, 1994;Berx et al, 1995;Vos et al, 1997). Loss of E-cadherin expression was reported in 85% of invasive lobular carcinomas (ILCs) and lobular carcinoma in situ (LCIS) (Sarrio et al, 2004;Yoder et al, 2007). However, ductal histology often presents with varying levels of expression associated with epigenetic transcriptional downregulation (Graff et al, 1995;Nass et al, 2000;Prasad et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

Asiaf

Ahmad²,

Aziz³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p= 0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

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Molecular and Morphologic Distinctions between Infiltrating Ductal and Lobular Carcinoma of the Breast

Cited by 68 publications

References 92 publications

The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology

The biological and clinical characteristics of breast carcinoma with mixed ductal and lobular morphology

P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer

Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir

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