The Prognostic Significance of P-Cadherin in Infiltrating Ductal Breast Carcinoma

Gamallo, Carlos; Moreno‐Bueno, Gema; Sarrió, David; Calero, Francisco Calero; Hardisson, David; Palacios, José

doi:10.1038/modpathol.3880367

Cited by 79 publications

(117 citation statements)

References 18 publications

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“…Examples of negative and positive tumours are shown in Figure 1k and l, respectively. In poorly di erentiated IDCs, a reduction in E-cadherin expression is frequently associated with anomalous P-cadherin expression, suggesting the presence of common regulatory mechanisms (Palacios et al, 1995;Gamallo et al, 2001). However, in this study no correlation between P-cadherin and Snail expression was observed (P=0.29).…”

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confidence: 54%

Correlation of Snail expression with histological grade and lymph node status in breast carcinomas

et al. 2002

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Snail is a zinc ®nger transcription factor that triggers the epithelial-mesenchymal transition (EMT) by directly repressing E-cadherin expression. Snail is required for mesoderm and neural crest formation during embryonic development and has recently been implicated in the EMT associated with tumour progression. In a series of human breast carcinomas, we have analysed the expression of Snail and that of molecules of the Ecadherin/catenin complexes. We have also correlated these data with the pathological features of the tumours. We show that Snail expression inversely correlates with the grade of di erentiation of the tumours and that it is expressed in all the in®ltrating ductal carcinomas (IDC) presenting lymph node metastases that were analysed. In addition, Snail is expressed in some dedi erentiated tumours with a negative nodal status. Considering that Snail is involved in the induction of the invasive and migratory phenotype in epithelial cells, these results indicate that it is also involved in the progression of breast ductal tumours, where it could additionally serve as a marker of the metastatic potential.

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confidence: 54%

Correlation of Snail expression with histological grade and lymph node status in breast carcinomas

et al. 2002

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“…Previous studies have shown that P-cadherin expression in breast carcinomas is able to identify a subgroup of lesions with a more aggressive behaviour and poor patient survival (Peralta Soler et al, 1999;Gamallo et al, 2001;Paredes et al, 2002Paredes et al, , 2004Paredes et al, , 2005Paredes et al, , 2008. Similar associations between P-cadherin expression and poor prognosis are described in other cancer models, namely endometrial, cervical, gastric and pancreatic carcinomas (Stefansson et al, 2004;Longatto Filho et al, 2005;Taniuchi et al, 2005).…”

Section: Discussionmentioning

confidence: 67%

“…In contrast, these tumours overexpress P-cadherin, maintaining the normal E-cadherin expression (Paredes et al, , 2008. In clinical terms, these P-cadherin-overexpressing tumours present high histological grade, with decreased cell polarity, aggressive behaviour and worse patient survival (Peralta Soler et al, 1999;Gamallo et al, 2001;Paredes et al, 2002Paredes et al, , 2005. On the basis of these observations, we aimed to understand how P-cadherin, in an E-cadherin wild-type background, could influence the behaviour of these tumours.…”

Section: Introductionmentioning

confidence: 99%

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

et al. 2009

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Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours.

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“…Several studies have linked the expression of basal markers to increased proliferation, absence of ER, a characteristic growth pattern, and poor prognosis. 79,80,87,88 Recently, Sorlie et al, 89 reanalyzing cDNA microarray data from van't Veer et al, 90 which included 18 BRCA1 and two BRCA2 carcinomas, observed that 80% of BRCA1 carcinomas had a basal-type gene expression profile. Subsequently, Foulkes et al 91 and Palacios et al 92 found a high prevalence of tumors with a basal phenotype among BRCA1-mutation carriers.…”

Section: Brca1 Carcinomas and The Basal Cell Phenotypementioning

confidence: 99%

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications

2005

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Cancer arising in carriers of mutations in the BRCA1 and BRCA2 genes differs from sporadic breast cancer of age-matched controls and from non-BRCA1/2 familial breast carcinomas in its morphological, immunophenotypic and molecular characteristics. Most BRCA1 carcinomas have the basal cell phenotype, a subtype of highgrade, highly proliferating, estrogen receptor-and HER2-negative breast carcinomas, characterized by the expression of basal or myoepithelial markers such as basal keratins, P-cadherin, epidermal growth factor receptor, etc. This phenotype is rarely found in BRCA2 carcinomas, which are of higher grade than sporadic age-matched controls, but tend to be estrogen receptor-and progesterone receptor-positive. The expression of the cell-cycle proteins cyclins A, B1 and E and SKP2 is associated with a BRCA1 phenotype, whereas cyclin D1 and p27 expression is associated with BRCA2 carcinomas. Recent studies have shown that hereditary carcinomas that are not attributable to BRCA1/2 mutations have phenotypic similarities to BRCA2 tumors, but tend to be of lower grade and proliferation index. Somatic mutations in the BRCA genes are rarely found in hereditary tumors; by contrast, BRCA1 and BRCA2 loss of heterozygosity (LOH) is found in almost all BRCA1 and BRCA2 carcinomas, respectively. Furthermore, all types of hereditary breast carcinomas have a low frequency of HER2 expression. Finally, comparative genomic hybridization studies have revealed differences in chromosomal gains and losses between genotypes. The pathological and molecular features of hereditary breast cancer can drive specific treatments and influence the process of mutation screening. In addition, detecting molecular changes such as BRCA1/2 LOH in nonatypical cells obtained by random fine-needle aspiration, ductal lavage or nipple aspirate fluid may help to earlier identify carrier women who are at an even higher risk of developing breast carcinoma. Keywords: hereditary breast cancer; BRCA1; BRCA2; molecular pathology; histopathology; immunohistochemistry It is currently estimated that 5-10% of all breast cancers are hereditary and attributable to mutations in high-penetrance susceptibility genes, but only two of these have been identified: BRCA1 (OMIM 113705) 1 and BRCA2 (OMIM 600185). 2 BRCA1 mutations are associated with families with breast and ovarian cancer, while families with male breast tumors are associated with mutations in the BRCA2 gene.While early estimates suggested that BRCA1 and BRCA2 mutations were responsible for 75% of multiple-case breast cancer families and for the majority of families with multiple breast and ovarian cancers, 3,4 recent data have shown that these percentages may have been overestimated. In fact, the percentage of high-risk families associated with mutations in these genes seems to be around 25% in all series investigated, including the Spanish population. 5 Mutations are found in a high percentage (about 45%) of families with breast and ovarian tumors, while the mutation rate in families with only breast can...

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The Prognostic Significance of P-Cadherin in Infiltrating Ductal Breast Carcinoma

Cited by 79 publications

References 18 publications

Correlation of Snail expression with histological grade and lymph node status in breast carcinomas

Correlation of Snail expression with histological grade and lymph node status in breast carcinomas

Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications

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