ISET Test

The ISET Test (Isolation by Size of Tumor cells / Trophoblastic cells) is a diagnostic blood test that detects circulating tumor cells in a blood sample.^[1][2][3] The test uses an in-vitro diagnostic system developed at INSERM, the Université Paris Descartes and Assistance Publique Hôpitaux de Paris (AP-HP) in order to isolate cancer cells from blood without loss and identify them through a diagnostic cytopathology-based approach.

Operation

A 1-ml sample of blood will typically contain 5 to 10 million leukocytes, 5 billion erythrocytes, and a small number of circulating rare cells, including:

• non-tumor cells such as epithelial-normal cells, epithelial-atypical cells, endothelial vells and stem cells;
• physiological state-dependent cells such as fetal cells in pregnant and ex-pregnant women;
• circulating tumor cells (CTCs) which are of diagnostic value in diagnosing various cancers.

The diagnostic problem is to find and identify the rare CTCs among the abundant other cells in a given blood sample.

The ISET technology is based on the observation that tumor cells of all types of solid cancers are larger than blood cells (leukocytes and erythrocytes). However, blood filtration to recover rare circulating tumor cells without loss and without cell damage is a challenge. The ISET test uses a specially designed device and specially designed filters to allow the elimination of all erythrocytes and most leukocytes from the sample, making the subsequent cytopathology process significantly easier and more accurate.

A circulating tumor cell (arrow) diagnosed by the ISET test. (The pores of the filter are also visible.)

Tumor and not-tumor cells present in blood. Tumor cells are marked by arrows. Adapted from Hofman et al., Clinical Cancer Research, 2011 (8) A, b, c: Tumor cells, d, e, f: Atypical cells, g, h, i:Normal cells.

Quality

Because ISET relies on cytopathology (i.e. specific visual identification of cancer cells) rather than isolating cells by biomarkers, its developers claim that the test has a relatively low false-positive rate. They also claim a 95% sensitivity rate (in 95% of samples in which CTCs are present, the ISET test will isolate the CTCs sufficiently for cytopathological identification). Published results indicate that the test is more sensitive and specific than CellSearch, the present FDA-approved metastatic cancer screening method, for

• non-small cell lung cancer
• breast cancer
• prostate cancer
• pancreatic cancer

History

The ISET technology was first reported in 2000 in the American Journal of Pathology by the team of Professor Patrizia Paterlini-Bréchot.

Since the first report in 2000, over 35 scientific articles have been published using the Rarecells System verifying the findings of the initial developers.

From 2005 to 2008, the device operating the ISET process was distributed by Metagenex. In 2009 Metagenex gave back the licences of the ISET patents to its developers: INSERM, University Paris Descartes and AP-HP. Paterlini-Bréchot then founded the company Rarecells^[4] which, since 2010, has the exclusive licence of the ISET patents, distributes the ISET products and develops the ISET tests.

Articles

• Krebs, M.; et al. (February 2012). "Analysis of Circulating Tumor Cells in Patients with Non-small Cell Lung Cancer Using Epithelial Marker-Dependent and -Independent Approaches". Journal of Thoracic Oncology. 7 (2): 306–315. doi:10.1097/jto.0b013e31823c5c16.
• Farace; et al. (September 2011). "A Direct Comparison of CellSearch™ and ISET® for Circulating Tumour-Cell Detection in Patients with Metastatic Carcinomas". British Journal of Cancer. 105 (6): 847–853. doi:10.1038/bjc.2011.294.
• Khoja, L.; et al. (January 31, 2012). "A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker". British Journal of Cancer. 106 (3): 508–516. doi:10.1038/bjc.2011.545.
• Khoja, L.; et al. (February 2013). "Prevalence and heterogeneity of circulating tumour cells in metastatic cutaneous melanoma". Melanoma Research. 24 (1): 40–46. doi:10.1097/cmr.0000000000000025.
• Hofman, V.; et al. (1 October 2011). "Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small cell lung carcinoma: Comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method®". International Journal of Cancer. 129 (7): 1651–1660. doi:10.1002/ijc.25819.
• Pailler, E.; et al. (20 June 2013). "Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non–small-cell lung cancer". Journal of Clinical Oncology. 31 (18): 2273–2281. doi:10.1200/jco.2012.44.5932.
• Vona, G.; et al. (January 2000). "ISET, Isolation by Size of Epithelial Tumor cells: a new method for isolation, immuno- morphological and molecular characteriza- tion of circulating tumor cells". American Journal of Pathology. 156 (1): 57–63.
• Hofman, V.; et al. (January 2011). "Cytopathologic Detection of Circulating Tumor Cells Using the Isolation by Size of Epithelial Tumor Cell Method". American Journal of Clinical Pathology. 135 (1): 146–156. doi:10.1309/ajcp9x8ozbeiqvvi.

Sources

1. "ISET : une prise de sang précoce pour dépister des maladies génétiques par Inserm dans Futura Santé du 13 décembre 2012.
2. "ISET : un test génétique prénatal à encadrer par Floriane Blanc dans Pour la science de novembre 2013.
3. "Cancer : une nouvelle méthode pronostique non invasive testée sur le cancer du foie" par INSERM dans Caducee.net du12 mai 2004.
4. "ISET Publications" by Rarecells in Rarecells Diagnostics.