p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer

Ribeiro‐Silva, Alfredo; Ramalho, Leandra Náira Zambelli; Garcia, Sérgio Britto; Brandão, Daniel Ferraciolli; Chahud, Fernando; Zucoloto, Sérgio

doi:10.1111/j.1365-2559.2005.02249.x

Cited by 82 publications

(87 citation statements)

References 33 publications

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“…Our study confirms and extends the previously reported findings of the basal-like carcinoma immunophenotype. [5][6][7][8]10 In addition, we demonstrate the presence of in situ carcinoma as the likely precursor lesion for invasive basal-like carcinoma.…”

Section: Discussionmentioning

confidence: 56%

“…5 The characteristic immunohistologic phenotype of these tumors is the 'triple negative' receptors of estrogen, progesterone and HER-2/neu, while expressing keratins CK5/6, CK14, CK17, vimentin and HER-1. [5][6][7][8][9][10][11] While the invasive basal-like neoplasms are reasonably well characterized morphologically and immunohistochemically, there is little data about the precursor lesion(s) for the entity.…”

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confidence: 99%

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Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

et al. 2006

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The basal phenotype of breast carcinoma was demonstrated from a study of gene expression profiles, which demonstrated five carcinoma phenotypes with differing immunohistologic profiles and outcomes. The basal phenotype, so-named because of an immunohistologic profile that is similar to myoepithelial cells of the breast, has poor outcomes. While the invasive basal phenotype has been described, there is a paucity of literature regarding the existence or recognition of a precursor lesion. We searched our CoPath database for breast carcinomas in the age group of 37 years or less, and this yielded 98 cases from the years 2001 to April 2006. Pathology reports were screened for those cases that were negative for estrogen and progesterone receptors and HER-2/neu (triple negative). A total of 16 cases (16/98, 16%) fulfilled these criteria. Histology was reviewed and immunostains were performed for Cytokeratins 14, 17, and 5/6, vimentin, EGFR, c-kit, smooth muscle actin and p63. All 16 cases had a high-grade invasive ductal carcinoma, Nottingham score 9/9, with geographic necrosis, good circumscription and lymphoid infiltrates. Of the 16 cases, 13 exhibited at least one area of ductal carcinoma in situ (DCIS). The DCIS types were solid, flat or micropapillary, high nuclear grade, with comedonecrosis and invariably associated with intense lymphoid inflammatory cell infiltration. Of 16 invasive cases, 14 (88%) were positive for CK14, CK17, CK5/6 and EGFR; 94% were vimentin positive, while half or less of cases were positive for smooth muscle actin, c-kit or p63. All of the DCIS components demonstrated the same immunohistologic profile as the invasive component. A DCIS component of solid, flat or micropapillary type exists in the basal phenotype of breast carcinoma, and it demonstrates the same immunophenotype as the invasive carcinoma, typically positive for CK5/6, CK14, CK17, vimentin and EGFR, but negative for ER/PR and HER-2/neu.

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Section: Discussionmentioning

confidence: 56%

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confidence: 99%

Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

et al. 2006

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“…Much of the confusion has arisen from the known difficulties with BRCA1 immunohistochemistry (Perez-Valles et al, 2001), especially in suboptimally fixed formalin sections. Although one small study found BRCA1 expression assessed by immunohistochemistry to be increased in basal-like cancers (Matros et al, 2005), this has been contradicted by larger studies that document reduced BRCA1 expression specifically in the basal-like cohort (Abd El-Rehim et al, 2005;Ribeiro-Silva et al, 2005). The finding of high ID4 expression, a known regulator of BRCA1 expression (Beger et al, 2001), in many basal-like cancers may in part explain the suppression of BRCA1 levels (NC Turner and JS Reis-Filho, unpublished observations).…”

Section: Brca1 Pathway In Sporadic Basal-like Cancersmentioning

confidence: 99%

Basal-like breast cancer and the BRCA1 phenotype

2006

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Breast cancers arising in germline carriers of BRCA1 mutations have a characteristic phenotype that has been shown in many studies to differentiate BRCA1 tumours from sporadic tumours. Recently, it has become clear that the characteristic phenotype of BRCA1 tumours is due to expression of the basal-like phenotype. We review these phenotypes, the evidence for BRCA1 pathway dysfunction in sporadic basal-like cancers, and discuss the clinical significance of the basal-like phenotype for cancer genetics and treatment.

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“…In any event, numerous studies have demonstrated p63 overexpression in up to 80% of primary head and neck squamous cell carcinomas (HNSCCs), and p63 overexpression is also commonly observed in other squamous epithelial cancers, including lung, nasopharyngeal, esophageal and cervical cancers (Wang et al, 2001; p63 and p73 in human cancer: defining the network MP DeYoung and LW Ellisen Hu et al, 2002;Weber et al, 2002;Massion et al, 2003;Sniezek et al, 2004). Reports have varied as to the frequency of p63 expression in invasive breast carcinomas, with studies ranging from 0 to 30% (Wang et al, 2002;Reis-Filho et al, 2003;Koker and Kleer, 2004;Ribeiro-Silva et al, 2005). It now seems clear, however, that p63 is expressed in at least a subset of breast tumors that are known to exhibit a basal epithelial phenotype (Perou et al, 2000).…”

Section: Expression and Mutation Of P63 And P73 In Human Cancermentioning

confidence: 99%

p63 and p73 in human cancer: defining the network

2007

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The p53-related genes p63 and p73 exhibit significant structural homology to p53; however, they do not function as classical tumor suppressors and are rarely mutated in human cancers. Both p63 and p73 exhibit tissue-specific roles in normal development and a complex contribution to tumorigenesis that is due to their expression as multiple protein isoforms. The predominant p63/p73 isoforms expressed both in normal development and in many tumors lack the conserved transactivation (TA) domain; these isoforms instead exhibit a truncated N-terminus (DN) and function at least in part as transcriptional repressors. p63 and p73 isoforms are regulated through both transcriptional and post-translational mechanisms, and they in turn regulate diverse cellular functions including proliferation, survival and differentiation. The net effect of p63/p73 expression in a given context depends on the ratio of TA/DN isoforms expressed, on physical interaction between p63 and p73 isoforms, and on functional interactions with p53 at the promoters of specific downstream target genes. These multifaceted interactions occur in diverse ways in tumor-specific contexts, demonstrating a functional 'p53 family network' in human tumorigenesis. Understanding the regulation and mechanistic contributions of p63 and p73 in human cancers may ultimately provide new therapeutic opportunities for a variety of these diseases.

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p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer

Abstract: Since p63 is thought to be a marker of stem cells and may act as an oncogene, our data support the idea that BRCA1 acts as stem cell regulator.

Cited by 82 publications

References 33 publications

Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

Basal-like breast cancer and the BRCA1 phenotype

p63 and p73 in human cancer: defining the network

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