Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel

Mitas, Michael; Mikhitarian, Kaidi; Walters, Christian; Baron, Paul L.; Elliott, Bruce M.; Robison, Jacob G.; Metcalf, John S.; Palesch, Yuko Y.; Zhang, Zhen; Gillanders, William E.; Cole, David J.

doi:10.1002/ijc.1312

Cited by 175 publications

(124 citation statements)

References 42 publications

(43 reference statements)

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…Recently, RT -PCR assays with tumour-specific gene markers such as CK19, CEA, MUC1, PIP, Mapsin and mammaglobin B have been widely used to detect occult metastasis in cancer patients (Noguchi et al, 1994(Noguchi et al, , 1996Schoenheld et al, 1994;Mori et al, 1995Mori et al, , 1998Kataoka et al, 2000;Masuda et al, 2000;Manzotti et al, 2001;Mitas et al, 2001). To date, however, no marker that is expressed in all breast cancer tissues, but not in normal lymph node has been available, partly because of the heterogeneity of marker gene expression in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…To date, however, no marker that is expressed in all breast cancer tissues, but not in normal lymph node has been available, partly because of the heterogeneity of marker gene expression in cancer cells. Therefore, multimarker analysis will probably be necessary for the precise and accurate examination of lymph node metastasis (Manzotti et al, 2001;Mitas et al, 2001). On the other hand, some evidence suggests that false positives may arise due to several factors, including illegitimate CK19 mRNA expression in lymphocytes, the presence of noncancerous epithelial cells in lymph nodes and the use of inappropriate primer modification and too many PCR amplification cycles (Bostic et al, 1998b).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Quantitative evaluation of metastases in axillary lymph nodes of breast cancer

et al. 2003

View full text Add to dashboard Cite

We have established a highly sensitive and quantitative reverse transcriptase -polymerase chain reaction (RT -PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metastases in 358 axillary lymph nodes obtained from 23 breast cancers of 22 patients were investigated by conventional haematoxylin and eosin (H&E) staining, immunohistochemical staining and quantitative RT -PCR assay. The detection rates of axillary lymph node metastasis using H&E staining, immunohistochemistry and RT -PCR assay were 4.5, 5.9 and 13.1%, respectively. RT -PCR assay was the most sensitive of these three methods for detecting lymph node metastases. Cytokeratin 19 mRNA expression values of both histologically and immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (Po0.0001), and those of histologically negative, but immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (Po0.0001). Furthermore, metastatic rates of sentinel nodes were higher than the rates of nonsentinel lymph nodes as measured by all three methods. These results indicate that quantitative RT -PCR assay is a sensitive and reliable method for detecting lymph node metastasis. Furthermore, quantification of metastases in sentinel lymph nodes by quantitative RT -PCR assay may be useful to assess the entire axillary burden of breast cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Quantitative evaluation of metastases in axillary lymph nodes of breast cancer

et al. 2003

View full text Add to dashboard Cite

show abstract

“…9), tumor suppressor genes (e.g., p53; ref. 194), and cell adhesion molecules (e.g., E-cadherin and P-cadherin; refs. [195][196][197][198] have been studied as possible breast tumor markers.…”

Section: Breast Cancer Biomarkersmentioning

confidence: 99%

The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer

Rodrigues

Teixeira

Schmitt

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

206

144

View full text Add to dashboard Cite

The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last few years. Progress in the development of consistent malignancy markers is imminent because advances in genomics and bioinformatics have allowed the examination of immense amounts of data. Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, and activated T lymphocytes, and is present in extracellular fluids, at sites of inflammation, and in the extracellular matrix of mineralized tissues. Several physiologic roles have been attributed to osteopontin, i.e., in inflammation and immune function, in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts with a variety of cell surface receptors, including several integrins and CD44. Binding of osteopontin to these cell surface receptors stimulates cell adhesion, migration, and specific signaling functions. Overexpression of osteopontin has been found in a variety of cancers, including breast cancer, lung cancer, colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover, osteopontin is present in elevated levels in the blood and plasma of some patients with metastatic cancers. Therefore, suppression of the action of osteopontin may confer significant therapeutic activity, and several strategies for bringing about this suppression have been identified. This review looks at the recent advances in understanding the possible mechanisms by which osteopontin may contribute functionally to malignancy, particularly in breast cancer. Furthermore, the measurement of osteopontin in the blood or tumors of patients with cancer, as a way of providing valuable prognostic information, will be discussed based on emerging clinical data. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1087 -97)

show abstract

“…Furthermore, the genes mammaglobin, epidermal growth factor receptor (EGFR) and SBEM were tested, described in the literature as breast cancer marker genes (De Luca et al, 2000;Mitas et al, 2001;Miksicek et al, 2002;Zehentner et al, 2002). For each gene, C T -values for negative control lymph nodes and metastatic breast cancer lymph nodes were obtained from triplicate reactions.…”

Section: Marker Gene Selection For the Detection Of Metastatic Breastmentioning

confidence: 99%

Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple mRNA markers

et al. 2004

View full text Add to dashboard Cite

Disseminated breast tumour cells in sentinel lymph nodes (SNs) were evaluated by quantitative real-time PCR and the sensitivity of this assay was compared to the routine histological analysis. First, several candidate marker genes were tested for their specificity in axillary lymph nodes (ALN) of 50 breast cancer patients and 43 women without breast cancer. The marker gene panel selected, designed to detect the mRNA of CK19, p1B, EGP2 and SBEM, was subsequently applied to detect metastases in 70 SNs that were free of metastases as determined by standard histological evaluation. Remarkably, seven negative SNs showed increased marker gene expression, suggesting the presence of (micro) metastases. Four of these seven SNs positive by real-time PCR proved to contain tumour deposits after careful review of the slides or further sectioning of the paraffin-embedded material. In three PCR positive SNs, however, no tumour cells were found by haematoxylin and eosin staining (H&E) and immunohistologically analysis. The quantitative real-time PCR assay with multiple mRNA markers for the detection of disseminated breast cancer cells in SNs thus resulted in an upstaging of SNs containing metastastic disease of 10% compared to the routine histological analysis. The application of this technique may be of clinical relevance, as it is suggested that micrometastatic disease in SNs are associated with further nodal non-SN metastases in breast cancer.

show abstract

Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel

Cited by 175 publications

References 42 publications

Quantitative evaluation of metastases in axillary lymph nodes of breast cancer

Quantitative evaluation of metastases in axillary lymph nodes of breast cancer

The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer

Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple mRNA markers

Contact Info

Product

Resources

About