Development of a New Method for Identification and Quantification in Cerebrospinal Fluid of Malignant Cells from Breast Carcinoma Leptomeningeal Metastasis

Overview

Journal BMC Clin Pathol

Publisher Biomed Central

Date 2012 Nov 14

PMID 23145812

Citations 31

Authors

Emilie Le Rhun

Frederic Massin

Qian Tu

Jacques Bonneterre

Marcelo De Carvalho Bittencourt

Gilbert C Faure

Affiliations

Soon will be listed here.

Abstract

Unlabelled:

Background: The diagnosis of leptomeningeal metastasis (LM) in patients with solid tumors remains difficult. The usual diagnostic methods of cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium enhanced MRI of the entire neuraxis lack both specificity and sensitivity. The Veridex CellSearch® technology has been designed for the detection of circulating tumor cells (CTC) in blood from cancer patients and validated for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer. Our aim was to adapt this technology for the detection and the enumeration of tumor cells in the CSF of breast cancer patients presenting with LM.

Methods: On the occasion of a randomized phase III study evaluating the role of the intrathecal treatment in LM from breast cancer (DEPOSEIN, EudraCT N°: 2010-023134-23), the CellSearch® technology was adapted to direct enrichment, enumeration and visualization of tumor cells in 5 mL CSF samples, collected on CellSave® Preservative Tubes and analyzed within 3 days after CSF sampling.

Results: Sixteen CSF of 8 patients with primary breast cancer presenting with LM were studied. EpCAM+/cytokeratin + cells with typical morphology could be observed and enumerated sequentially with reproducible results in low or elevated numbers in 8 patients.

Conclusion: This methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of cancer patients with LM, especially to appreciate the efficacy of chemotherapy.

Citing Articles

Early Hints of Metagenome Next-Generation Sequencing and Copy Number Variations Analysis: An Occult Case of Leptomeningeal Metastasis With Rapid Cognitive Decline.

Chen X, Zheng H, Wang T, Feng Z, Wang J, Liu Y Clin Case Rep. 2024; 12(12):e9676.

PMID: 39624075 PMC: 11609582. DOI: 10.1002/ccr3.9676.

Clinical application of circulating tumor cells.

Stoecklein N, Oles J, Franken A, Neubauer H, Terstappen L, Neves R Med Genet. 2024; 35(4):237-250.

PMID: 38835741 PMC: 11110132. DOI: 10.1515/medgen-2023-2056.

A brain metastasis liquid biopsy: Where are we now?.

Robinson S, de Boisanger J, Pearl F, Critchley G, Rosenfelder N, Giamas G Neurooncol Adv. 2024; 6(1):vdae066.

PMID: 38770219 PMC: 11102938. DOI: 10.1093/noajnl/vdae066.

Double-dose osimertinib combined with intrathecal injection of pemetrexed improves the efficacy of EGFR-mutant non-small cell lung cancer and leptomeningeal metastasis: case report and literature review.

Zhong W, Wu L, Huang L, Wang J, Shi H, Wu S Front Oncol. 2024; 14:1377451.

PMID: 38711856 PMC: 11070505. DOI: 10.3389/fonc.2024.1377451.

New Breakthroughs in the Diagnosis of Leptomeningeal Carcinomatosis: A Review of Liquid Biopsies of Cerebrospinal Fluid.

Goldberg M, Mondragon-Soto M, Altawalbeh G, Meyer B, Aftahy A Cureus. 2024; 16(2):e55187.

PMID: 38558729 PMC: 10980855. DOI: 10.7759/cureus.55187.

References

Weston C, Glantz M, Connor J . Detection of cancer cells in the cerebrospinal fluid: current methods and future directions. Fluids Barriers CNS. 2011; 8(1):14. PMC: 3059292. DOI: 10.1186/2045-8118-8-14. View

Allard W, Matera J, Miller M, Repollet M, Connelly M, Rao C . Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004; 10(20):6897-904. DOI: 10.1158/1078-0432.CCR-04-0378. View

Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B . Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res. 2007; 13(3):920-8. DOI: 10.1158/1078-0432.CCR-06-1695. View

Tarnok A, Bocsi J, Brockhoff G . Cytomics - importance of multimodal analysis of cell function and proliferation in oncology. Cell Prolif. 2006; 39(6):495-505. PMC: 6496464. DOI: 10.1111/j.1365-2184.2006.00407.x. View

Patel A, Allen J, Dicker D, Peters K, Sheehan J, Glantz M . Identification and enumeration of circulating tumor cells in the cerebrospinal fluid of breast cancer patients with central nervous system metastases. Oncotarget. 2011; 2(10):752-60. PMC: 3248154. DOI: 10.18632/oncotarget.336. View

Rompp A, Dekker L, Taban I, Jenster G, Boogerd W, Bonfrer H . Identification of leptomeningeal metastasis-related proteins in cerebrospinal fluid of patients with breast cancer by a combination of MALDI-TOF, MALDI-FTICR and nanoLC-FTICR MS. Proteomics. 2007; 7(3):474-81. DOI: 10.1002/pmic.200600719. View

Corsini E, Bernardi G, Gaviani P, Silvani A, de Grazia U, Ciusani E . Intrathecal synthesis of tumor markers is a highly sensitive test in the diagnosis of leptomeningeal metastasis from solid cancers. Clin Chem Lab Med. 2009; 47(7):874-9. DOI: 10.1515/CCLM.2009.183. View

Groves M . New strategies in the management of leptomeningeal metastases. Arch Neurol. 2010; 67(3):305-12. DOI: 10.1001/archneurol.2010.18. View

Gauthier H, Guilhaume M, Bidard F, Pierga J, Girre V, Cottu P . Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol. 2010; 21(11):2183-2187. DOI: 10.1093/annonc/mdq232. View

10.

Rudnicka H, Niwinska A, Murawska M . Breast cancer leptomeningeal metastasis--the role of multimodality treatment. J Neurooncol. 2007; 84(1):57-62. DOI: 10.1007/s11060-007-9340-4. View

11.

Clatot F, Philippin-Lauridant G, Ouvrier M, Nakry T, Laberge-Le-Couteulx S, Guillemet C . Clinical improvement and survival in breast cancer leptomeningeal metastasis correlate with the cytologic response to intrathecal chemotherapy. J Neurooncol. 2009; 95(3):421-426. DOI: 10.1007/s11060-009-9940-2. View

12.

Lee S, Ahn H, Park Y, Nam D, Lee J, Park W . Leptomeningeal metastases from breast cancer: intrinsic subtypes may affect unique clinical manifestations. Breast Cancer Res Treat. 2011; 129(3):809-17. DOI: 10.1007/s10549-011-1682-0. View

13.

de Azevedo C, Cruz M, Chinen L, Peres S, Peterlevitz M, Pereira A . Meningeal carcinomatosis in breast cancer: prognostic factors and outcome. J Neurooncol. 2011; 104(2):565-72. DOI: 10.1007/s11060-010-0524-y. View

14.

Nayak L, Fleisher M, Gonzalez-Espinoza R, Lin O, Panageas K, Reiner A . Rare cell capture technology for the diagnosis of leptomeningeal metastasis in solid tumors. Neurology. 2013; 80(17):1598-605. PMC: 3662321. DOI: 10.1212/WNL.0b013e31828f183f. View

15.

Chamberlain M, Glantz M, Groves M, Wilson W . Diagnostic tools for neoplastic meningitis: detecting disease, identifying patient risk, and determining benefit of treatment. Semin Oncol. 2009; 36(4 Suppl 2):S35-45. DOI: 10.1053/j.seminoncol.2009.05.005. View

16.

Glantz M, Cole B, Glantz L, Cobb J, Mills P, Lekos A . Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer. 1998; 82(4):733-9. DOI: 10.1002/(sici)1097-0142(19980215)82:4<733::aid-cncr17>3.0.co;2-z. View

17.

Dux R, Kindler-Rohrborn A, Annas M, Faustmann P, Lennartz K, Zimmermann C . A standardized protocol for flow cytometric analysis of cells isolated from cerebrospinal fluid. J Neurol Sci. 1994; 121(1):74-8. DOI: 10.1016/0022-510x(94)90159-7. View

18.

Chamberlain M . Leptomeningeal metastases in the MRI era. Neurology. 2011; 76(2):200. DOI: 10.1212/WNL.0b013e3181fac738. View

19.

Walbert T, Groves M . Known and emerging biomarkers of leptomeningeal metastasis and its response to treatment. Future Oncol. 2010; 6(2):287-97. DOI: 10.2217/fon.09.167. View

20.

Chamberlain M . Leptomeningeal metastasis. Curr Opin Oncol. 2010; 22(6):627-35. DOI: 10.1097/CCO.0b013e32833de986. View