The case for early detection

Etzioni, Ruth; Urban, Nicole; Ramsey, Scott D.; McIntosh, Martin W.; Schwartz, Stephen M.; Reid, Brian J.; Radich, Jerald P.; Anderson, Garnet L.; Hartwell, Leland H.

doi:10.1038/nrc1041

Cited by 1,034 publications

(772 citation statements)

References 71 publications

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“…It is now well established that the earlier the diagnosis of cancer, the better the clinical outcome, through earlier administration of effective and possibly curative treatments (Etzioni et al, 2003). For colorectal cancer (CRC) the only curative treatment is surgery.…”

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confidence: 99%

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT–PCR

et al. 2006

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Accurate identification of lymph node involvement is critical for successful treatment of patients with colorectal carcinoma (CRC). Real-time quantitative RT -PCR with a specific probe and RNA copy standard for biomarker mRNA has proven very powerful for detection of disseminated tumour cells. Which properties of biomarker mRNAs are important for identification of disseminated CRC cells? Seven biomarker candidates, CEA, CEACAM1-S/L, CEACAM6, CEACAM7-1/2, MUC2, MMP7 and CK20, were compared in a test-set of lymph nodes from 51 CRC patients (Dukes' A -D) and 10 controls. Normal colon epithelial cells, primary tumours, and different immune cells were also analysed. The biomarkers were ranked according to: (1) detection of haematoxylin/eosin positive nodes, (2) detection of Dukes' A and B patients, who developed metastases during a 54 months follow-up period and (3) identification of patients with Dukes' C and D tumours using the highest value of control nodes as cutoff. The following properties appear to be of importance; (a) no expression in immune cells, (b) relatively high and constant expression in tumour tissue irrespective of Dukes' stage and (c) no or weak downregulation in tumours compared to normal tissue. CEA fulfilled these criteria best, followed by CK20 and MUC2.

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confidence: 99%

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT–PCR

et al. 2006

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“…When lung cancer is diagnosed at a localised stage, the 5-year survival is about 50%. In contrast, its prognosis is very poor when diagnosed with lymph node involvement or metastases, and the 5-year survival is then 8 and 3%, respectively (Etzioni et al, 2003). Several mechanisms are involved in the spread of metastatic cancer cells from the primary tumour, and degradation of the extracellular matrix (ECM) is an important process involving a variety of matrix-degrading proteinases.…”

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confidence: 99%

Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer

et al. 2005

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Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor that inhibits plasmin-dependent activation of several metalloproteinases. Downregulation of TFPI-2 could thus enhance the invasive potential of neoplastic cells in several cancers, including lung cancer. In this study, TFPI-2 mRNA was measured using a real-time PCR method in tumours of 59 patients with nonsmall-cell lung cancer (NSCLC). Tumour TFPI-2 mRNA levels appeared well correlated with protein expression evaluated by immunohistochemistry and were 4 -120 times lower compared to those of nonaffected lung tissue in 22 cases (37%). Hypermethylation of the TFPI-2 gene promoter was demonstrated by restriction enzyme-polymerase chain reaction in 12 of 40 cases of NSCLC (30%), including nine of 17 for whom tumour TFPI-2 gene expression was lower than in noncancerous tissue. In contrast, this epigenetic modification was shown in only three of 23 tumours in which no decrease in TFPI-2 synthesis was found (P ¼ 0.016). Decreased TFPI-2 gene expression and hypermethylation were more frequently associated with stages III or IV NSCLC (eight out of 10, P ¼ 0.02) and the TFPI-2 gene promoter was more frequently hypermethylated in patients with lymph node metastases (eight out of 16, P ¼ 0.02). These results suggest that silencing of the TFPI-2 gene by hypermethylation might contribute to tumour progression in NSCLC.

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“…Early detection of neoplasia, when the tumor is less than 1 mm in size, would theoretically be associated with long-term survival [30]. However, conventional anatomical imaging techniques typically detect neoplasia of 1 cm volume or larger (containing about 1 million cells) greatly decreasing survival [31].…”

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confidence: 99%