Distinctive gene expression patterns in human mammary epithelial cells and breast cancers

Perou, Charles M.; Jeffrey, Stefanie S.; Rijn, Matt van de; Rees, Christian A.; Eisen, Michael B.; Ross, Douglas T.; Pergamenschikov, Alexander; Williams, Cheryl F.; Zhu, Shirley; Lee, Jeffrey C. F.; Lashkari, Deval; Shalon, Dari; Brown, Patrick O.; Botstein, David

doi:10.1073/pnas.96.16.9212

Cited by 1,211 publications

(760 citation statements)

References 36 publications

(33 reference statements)

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“…In recent years, gene expression profiling data have further refined the subtypes of breast carcinomas. [1][2][3][4]12 Among the five subgroups (luminal A, luminal B, normal breast-like, ERB2 þ and basal-like) of breast carcinoma identified by gene expression profiling, most attention has been given to basal-like carcinoma. The possible interest is due to the fact that these tumors were not well recognized before the expression profiling, but in retrospect they seem to have a relatively specific immunohistologic profile.…”

Section: Discussionmentioning

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: 99%

“…[1][2][3][4] As the recognition of the different epithelial phenotypes become more widespread, tailored therapeutic strategies may become more important.…”

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confidence: 99%

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

et al. 2006

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“…For gene expression profiling by DNA microarray analysis, fluorescent cDNA probes were prepared from a 1-g experimental mRNA sample by oligo(dT)-primed polymerization using Superscript II reverse transcriptase in the presence of Cy5-labeled dCTP as described (online at http://cmgm.stanford.edu/pbrown/ protocols.html). A common reference mRNA sample that consists of a mixture of mRNA isolated from 11 different cell lines (15), synovial tissue, fibroblasts, and activated peripheral blood mononuclear cells was labeled with Cy3.…”

Section: Methodsmentioning

confidence: 99%

“…A powerful way to gain insight into the molecular complexity and pathogenesis of arthritides has arisen from complementary DNA (cDNA) microarray technology (11)(12)(13)(14)(15)(16)(17), which provides the opportunity to determine differences in gene expression of a large portion of the genome in search of genes that are differently expressed between clinically diagnosed arthritides (18). Therefore, we used microarrays containing ϳ18,000 cDNA representing predominantly genes thought to be of relevance in immunology.…”

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confidence: 99%

Rheumatoid arthritis is a heterogeneous disease: Evidence for differences in the activation of the STAT‐1 pathway between rheumatoid tissues

Kraan

Gaalen

Kasperkovitz

et al. 2003

Arthritis & Rheumatism

236

176

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ObjectiveTo generate a molecular description of synovial tissue from rheumatoid arthritis (RA) patients that would allow us to unravel novel aspects of pathogenesis and to identify different forms of disease.MethodsWe applied complementary DNA microarray analysis to profile gene expression, with a focus on immune‐related genes, in affected joint tissues from RA patients and in tissues from osteoarthritis (OA) patients as a control. To validate microarray data, real‐time polymerase chain reaction was performed on genes of interest.ResultsThe gene expression signatures of synovial tissues from RA patients showed considerable variability, resulting in the identification of at least two molecularly distinct forms of RA tissues. One class of tissues revealed abundant expression of clusters of genes indicative of an involvement of the adaptive immune response. Detailed analysis of the expression profile provided evidence for a prominent role of an activated signal transducer and activator of transcription 1 pathway in these tissues. The expression profiles of another group of RA tissues revealed an increased tissue remodeling activity and a low inflammatory gene expression signature. The gene expression pattern in the latter tissues was reminiscent of that observed in the majority of OA tissues.ConclusionThe differences in the gene expression profiles provide a unique perspective for distinguishing different pathogenetic RA subsets based on molecular criteria. These data reflect important aspects of molecular variation that are relevant for understanding the biologic dysregulation underlying these subsets of RA. This approach may also help to define homogeneous groups for clinical studies and evaluation of targeted therapies.

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“…Details of microarray construction were described previously. 7,8 After confirmation of the presence of viable tumor by frozen section, the frozen tissue was homogenized in Trizol reagent (Invitrogen, Carlsbad, CA, USA) and total RNA was extracted. Preparation of Cy-3-dUTP-labeled cDNA from reference RNA (Stratagen, Universal human reference RNA, catalog no.…”

Section: Rna Extraction and Cdna Microarray Analysismentioning

confidence: 99%

Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone

et al. 2008

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Giant cell tumor of the bone (GCTOB) is a primary bone tumor that occurs mainly in young adults and is capable of locally aggressive growth. Its histologic appearance can resemble a number of benign and malignant tumors but no useful diagnostic marker is known currently. To identify diagnostic markers for this tumor, global gene expression profiling using cDNA microarray was performed on 6 fresh-frozen GCTOB, 3 aneurysmal bone cysts, 4 fibrous dysplasias and 12 giant cell tumors of tendon sheath/diffuse-type giant cell tumors. Unsupervised hierarchical clustering separated the tumors based on their histopathologic types, and significance analysis of microarray identified several genes including TP73L (encoding the p63 protein) that are significantly highly expressed in GCTOB relative to these other tumors. The diagnostic utility of p63 was subsequently confirmed using anti-p63 antibody on a series of 26 GCTOB, 25 aneurysmal bone cysts, 15 chondroblastomas, 13 giant cell reparative granulomas, 13 chondromyxoid fibromas, 4 brown tumors, 4 fibrous dysplasias, 53 giant cell tumors of tendon sheath/diffuse-type giant cell tumors and 385 additional mesenchymal tumors in tissue microarrays. Strong p63 nuclear staining was present in 18 of 26 (69%) GCTOB, 3 of 15 (20%) chondroblastomas and in 1 of 25 (4%) aneurysmal bone cysts while none of the other tumors commonly considered in the differential diagnosis of GCTOB showed any detectable p63 staining. Strong p63 staining is rare in bone and soft-tissue tumors in general. In contrast to the pattern of p63 staining, the majority of the chondroblastomas (70%) demonstrated S-100 immunoreactivity while only a minority of the GCTOB (8%) was immunoreactive for S-100. These findings altogether show that p63 can be used as a diagnostic marker to aid the clinical diagnosis of GCTOB.

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Distinctive gene expression patterns in human mammary epithelial cells and breast cancers

Cited by 1,211 publications

References 36 publications

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

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

Rheumatoid arthritis is a heterogeneous disease: Evidence for differences in the activation of the STAT‐1 pathway between rheumatoid tissues

Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone

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