Pesquisa de Células Tumorais Circulantes

13.06.2013

Teste Sanguíneo para Pesquisa de Células Tumorais Circulantes

A presença de células tumorais circulantes (CTC) foi primeiramente descrita em 1869 pelo australiano Thomas Ashworth1. Vinte anos mais tarde, Steve Paget descreveu “A hipótese da semente e do solo”, na primeira edição do The Lancet, sengundo a qual, as metástases dependiam da inteiração entre a célula tumoral específica (semente) e um ambiente favorável no órgão receptor (solo), que foi revisada muitos anos depois por Fidler2.

Atualmente, o tema tem sido amplamente discutido em pesquisas clínicas sobre câncer e novos testes laboratoriais têm sido lançados com o intuito de detecção precoce de CTCs3. O papel crítico que as CTCs desempenham na propagação metastática de carcinomas é amplamente reconhecido4-6. Diversos estudos demonstraram a importância clínica das células tumorais disseminadas na medula óssea de pacientes com câncer de mama7.

A detecção e enumeração de CTCs foram estabelecidas em vários estudos clínicos, em que os resultados mostraram correlação com a diminuição de sobrevida livre de progressão e sobrevida global nos casos de câncer de mama operável8-12, antes e após a quimioterapia13. Em 2004, Cristofanilli et al. demostraram a importância da detecção de CTCs para a estimativa de progressão da doença e a sobrevivência no câncer de mama metastático14.

A pesquisa de CTCs é um novo e promissor campo diagnóstico para pacientes com câncer em estágios avançados. No entanto, devido à escassez de CTCs nas amostras clínicas, os testes apresentam limitações e grandes desafios analíticos. Diversos estudos sugerem que a pesquisa de CTCs produz importantes informações para a estratificação de risco e monitoramento da eficácia terapêutica em alguns tipos de tumor13. A American Association for Cancer Research-FDA-National Cancer Institute publicou em 201014recomendações e padronizações sobre a utilização dos testes para o diagnóstico de CTCs.

O único teste até então com aprovação pelo FDA chama-se Cell Search(Veridex LLC, Johnson and Johnson). O teste teve aprovação para a pesquisa de CTCs em casos de câncer de mama, colon e próstata. É realizado em amostras de sangue, que devem ser coletados em tubos e horários especiais. O teste é realizado com apoio do Mayo Medical Laboratories (EUA).

ENGLISH

Blood Test for Circulating Tumor Cell Research

The presence of circulating tumor cells (CTC) was first described in 1869 by th Australian Thomas Ashworth1. Twenty years later, Steve Paget described “The hypothesis of seed and soil”, in the first edition of The Lancet, in which,“metastases depended on integration between the tumor cell specific (seed) and a favorable environment in the receiving body (ground)”, which was reviewed many years after by Fidler2.

Currently, the topic has been extensively discussed  in clinical research on cancer and new laboratory tests have been launched with the aim of early detection of CTCs3. The critical role that circulating tumor cells up on the of carcinomas metastatic spread is widely reconized 4-6. Several studies have demonstrated the clinical significance of disseminated tumor cells in bone marrow from breast cancer7.

The detection and enumeration of CTCs were established in several clinical studies, where the results correlated with decreased progression-free survival and overall survival in cases of cirurgically operable breast cancer8-12, before and after chemotherapy13. In 2004, Cristofanilli et al. demonstrated the importance of detecting CTCs for predicting disease progression and survival in metastatic breast cancer14.

The research of CTCs is a new and promising field diagnosis for cancer patients in advanced stages. However, due to shortage of CTCs in clinical samples, the tests have limitations and analytical challenges. Several studies suggest that CTCs research produces important information for risk stratification and monitoring of therapeutic efficacy in some types of tumor13. The American Association for Cancer Research, FDA, National Cancer Institute published recommendations and standards at 2010 14 on the use of diagnostic tests for CTCs.

The only test so far with approval by the FDA is called Cell Search (Veridex LLC, Johnson and Johnson). The test was approved for the detection of CTCs in cases of breast, colon and prostate. It is performed on blood samples that must be collected in special tubes and schedules. The test is performed with the support of Mayo Medical Laboratories (USA).

Referências Bibliográficas:

  1. Ashworth TR. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Med J Australia 1869;14:146–7.
  2. Fidler IJ. The pathogenesis of cancer metastasis:the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 2003;3:453– 8.
  3. Kaiser J. Cancer’s circulation problem. Science (Wash DC) 2010;327:1072– .
  4. Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol 2009;6:339–51.
  5. Hayes DF, Smerage JR. Is there a role for circulating tumor cells in the management of breast cancer? Clin Cancer Res 2008;14:3646 –50.
  6. Kasimir-Bauer S. Circulating tumor cells as markers for cancer risk assessment and treatment monitoring. Mol Diagn Ther 2009;13:209 –15.
  7. Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005;353:793– 802.
  8. Stathopoulou A, Mavroudis D, Perraki M, Apostolaki S, Vlachonikolis I, Lianidou E, Georgoulias V. Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance. J Clin Oncol 2002;20:3404–12.
  9. Xenidis N, Vlachonikolis I, Mavroudis D, Perraki M, Stathopoulou A, Lianidou E, et al. Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer. Ann Oncol 2003;14:849 –55.
  10. Xenidis N, Perraki M, Kafousi M, Apostolaki S,Lianidou ES, Georgoulias V, et al. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in nodenegative breast cancer patients. J Clin Oncol 2006;24:3756–62.
  11. Ignatiadis M, Kallergi G, Ntoulia M, Lianidou E,Georgoulias V, Mavroudis D, et al. Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer. Clin Cancer Res 2008;14:2593– 600.
  12. Ignatiadis M, Xenidis N, Perraki M, Lianidou E, Sotiriou C, Georgoulias V, et al. Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer. J Clin Oncol 2007;25:5194 –202.
  13. Liannidou E.S. and Markou Athina. Circulating Tumor Cells in Breast Cancer: Detection Systems, Molecular Characterization, and Future Challenges. Clin Chem 2011; 57:9, 1242-55.
  14. Khleif SN, Doroshow JH, Hait WN. AACR-FDA-NCI Cancer Biomarkers Collaborative. AACR-FDA-NCI Cancer Biomarkers Collaborative consensus report: advancing the use of biomarkers in cancer drug development. Clin Cancer Res. 2010;16:3299–318.