Prostate-Specific Ets (PSE) factor: a novel marker for detection of metastatic breast cancer in axillary lymph nodes

Mitas, Michael; Mikhitarian, Kaidi; Hoover, Loretta L.; Lockett, Mark; Kelley, Laura A.; Hill, Arnold D.; Gillanders, William E.; Cole, David J.

doi:10.1038/sj.bjc.6600190

Cited by 43 publications

(27 citation statements)

References 19 publications

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“…Intronspanning primers were designed and tested in breast cancer cell lines MDA-MB-231 or SK-BR-3: TFF1 forward 5V -AATGGCCACCATGGA-GAACA-3V , reverse 5V -ACCACAATTCTGTCTTTCACGG-3V ; TFF3 forward 5V -TTTGACTCCAGGATCCCTGGAG-3V , reverse 5V -AGGTGCCTCA-GAAGGTGCATTC-3V ; PRO1708 forward 5V -AAGAATGCCCTGTGCA-GAAGAC-3V , reverse 5V -TTCTGTGCAGCATTTGGTGACT-3V ; Lipophilin B forward 5V -ACGGATCAGATGTCCCTTCAG-3V , reverse 5V -TTGAAAGA-CAGTGGAAACCAGG-3V ; FBJ forward 5V -CGTTGTGAAGACCATGA-CAGGA-3V , reverse 5V -TCCTTTCCCTTCGGATTCTCC-3V . Primers to the mam gene has been previously described (11,12). cDNA was made from 5 Ag of total RNA using 200 units of Moloney murine leukemia virus reverse transcriptase (Promega, Madison, WI) and 0.5 Ag Oligo (dT) [12][13][14][15][16] in a reaction volume of 20 AL (10 minutes at 70jC, 50 minutes at 42jC, and 15 minutes at 70jC).…”

Section: Methodsmentioning

confidence: 99%

“…Primers to the mam gene has been previously described (11,12). cDNA was made from 5 Ag of total RNA using 200 units of Moloney murine leukemia virus reverse transcriptase (Promega, Madison, WI) and 0.5 Ag Oligo (dT) [12][13][14][15][16] in a reaction volume of 20 AL (10 minutes at 70jC, 50 minutes at 42jC, and 15 minutes at 70jC). Real-time RT-PCR analysis was done on a PE Biosystems Gene Amp 5700 Sequence Detection System (Foster City, CA).…”

Section: Methodsmentioning

confidence: 99%

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An Innovative Microarray Strategy Identities Informative Molecular Markers for the Detection of Micrometastatic Breast Cancer

Mikhitarian¹,

Gillanders²,

Almeida³

et al. 2005

Clinical Cancer Research

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There is increasing evidence that molecular detection of micrometastatic breast cancer in the axillary lymph nodes (ALN) of breast cancer patients can improve staging. Molecular analyses of samples obtained from the Minimally Invasive Molecular Staging of Breast Cancer Trial (n = 489 patients) indicate that whereas the majority of molecular markers are informative for the detection of metastatic breast cancer (significant disease burden), only a few are sensitive for the detection of micrometastatic disease (limited disease burden). Frequency distribution and linear regression analyses reveal that relative levels of gene expression are highly correlated with apparent sensitivity for the detection of micrometastic breast cancer (P < 0.05). These data provides statistical validation of the concept that the most informative markers for detection of micrometastatic disease are those that are most highly expressed in metastatic disease. To test this hypothesis, we developed an innovative microarray strategy. RNA from a metastatic breast cancer ALN was diluted into RNA from a normal lymph node and analyzed using Affymetrix microarrays. Expression analysis indicated that only two genes [mammaglobin (mam) and trefoil factor 1 (TFF1)] were significantly overexpressed at a dilution of 1:50. Real-time reverse transcription-PCR analysis of pathology-negative ALN (n = 72) confirm that of all the markers tested, mam and TFF1 have the highest apparent sensitivity for detection of micrometastatic breast cancer. We conclude that a dilutional microarray approach is a simple and reliable method for the identification of informative molecular markers for the detection of micrometastatic cancer.A major focus of current research is the application of recent advances in molecular genetics to the field of surgical pathology and the detection of metastatic and micrometastatic cancer. In this context, metastatic cancer is defined as metastatic cancer of significant disease burden that is readily detected by standard histopathologic techniques, whereas micrometastatic cancer is defined as metastatic cancer of limited disease burden that cannot be detected by standard histopathologic techniques. In the setting of breast cancer, the presence of metastatic breast cancer in axillary lymph nodes (ALN) remains one of the most important prognostic factors for predicting disease recurrence (1 -3). Unfortunately, standard H&E histopathologic analysis of ALN has limitations, as it is subjective in nature and often lacks the sensitivity to detect small amounts of clinically relevant disease. A number of studies have shown that doing additional tissue sections and/or immunohistochemical staining (IHC) of ALN increases the ability to detect breast cancer metastases by up to 25% (4 -6). Furthermore, these retrospective studies suggest that the prognosis for patients with micrometastatic is similar to patients with pathologypositive ALN (4, 5, 7). Taken together, these findings suggest that the development of more sensitive histopathologic or m...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

An Innovative Microarray Strategy Identities Informative Molecular Markers for the Detection of Micrometastatic Breast Cancer

Mikhitarian¹,

Gillanders²,

Almeida³

et al. 2005

Clinical Cancer Research

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“…These transcription factors regulate a number of biological processes, including cell proliferation, differentiation and invasion and are thought to play an important role in oncogenesis. Unlike the majority of Ets factors, SPDEF is expressed exclusively in tissues with a high epithelial content, such as the prostate and the breast (Oettgen et al 2000, Ghadersohi & Sood 2001, Mitas et al 2002. Furthermore, several studies showed SPDEF to be one of the most highly overexpressed mRNAs in human and mouse mammary tumours (Ghadersohi & Sood 2001, Mitas et al 2002, Galang et al 2004.…”

Section: Spdefmentioning

confidence: 99%

Significance, detection and markers of disseminated breast cancer cells

Lacroix¹

2006

Endocr Relat Cancer

261

220

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The development of distant metastases is the major cause of death from breast cancer. In order to predict and prevent tumour spreading, many attempts are being made to detect small numbers of tumour cells that have shed from the primary lesions and have moved to lymph nodes, blood or bone marrow. This article presents the advantages and the limitations of techniques used for disseminated tumour cells (DTC) detection. DTC markers are listed and the most currently used of them (KRT19, CEACAM5, TACSTD1, MUC1, EGFR, ERBB2, SCGB2A2, SCGB2A1, SCGB1D2, PIP, SBEM, TFF1, TFF3, ANKRD30A, SPDEF, ESR1, SERPINB5 and GABRP) are discussed, notably on the basis of recent data on breast tumour portraits (luminal epithelial-like, basal/myoepithelial-like and ERBB2). The significance of DTC for the prognosis and prediction of response to therapy is examined. DTC viability, the notion of cell dormancy and the concept of breast cancer stem cells are also discussed.

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“…29,30 Porphobilinogen deaminase 31 and ␤-actin were used as housekeeping genes. Primers and hydrolysis probes for each assay are listed in Table 2.…”

Section: Reverse Transcription and Quantitative Polymerase Chain Reacmentioning

confidence: 99%

Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

Backus¹,

Laughlin²,

Wang³

et al. 2005

The Journal of Molecular Diagnostics

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Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin-and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection. Breast cancer is second only to lung cancer in mortality among women worldwide.1 In the care of this significant disease, the evaluation of blood, bone marrow, and lymph nodes for the presence of metastatic cells is an important component of disease characterization and management.2-6 The method for assessment of these peripheral tissues is largely dependent on histological and cytological methods. Detection of metastasis in lymph nodes is typically accomplished by hematoxylin and eosin (H&E) and antibody staining of lymph node sections.7,8 Analysis of bone marrow samples, although still in development, currently involves antibody staining of cytological smears. For some time, there has been discussion about the potential for the use of molecular biological tools to supplement or to improve existing methods.9 Molecular methods such as reverse transcriptase-polymerase chain reaction (RT-PCR) offer increased analytical sensitivity compared with standard histological methods. 10 -12 In addition, nucleic acid-based detection methods such as real-time PCR offer the potential of rapid and sensitive point-of-care testing and the application of objective quantitative assay cut-offs.A clear intersection between these features is the intraoperative assessment of sentinel lymph nodes (SLNs) for the presence of clinically actionable metastasis, a level of metastasis that would be expected to consistently lead to a subsequent axillary lymph node (ALN) dissecti...

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Prostate-Specific Ets (PSE) factor: a novel marker for detection of metastatic breast cancer in axillary lymph nodes

Cited by 43 publications

References 19 publications

An Innovative Microarray Strategy Identities Informative Molecular Markers for the Detection of Micrometastatic Breast Cancer

An Innovative Microarray Strategy Identities Informative Molecular Markers for the Detection of Micrometastatic Breast Cancer

Significance, detection and markers of disseminated breast cancer cells

Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

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