Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration

Eur J Endocrinol. 2008 Sep;159(3):283-91. doi: 10.1530/EJE-08-0190. Epub 2008 Jun 26.

Abstract

Objective: Anaplastic thyroid cancer (ATC) is often unoperable and chemotherapy and radiotherapy are the main treatments. Until now 'primary ATC cell cultures' (ANA) have been developed from surgical biopsies. The possibility to obtain ANA from fine-needle aspiration (FNA-ANA) and to test their sensitivity to different drugs could increase the effectiveness of treatments and avoid unnecessary surgical procedures.

Design: To obtain FNA-ANA from six ATC patients before undergoing surgery and to evaluate the chemosensitivity of FNA-ANA to chemotherapeutic agents and thiazolidinediones (TZD).

Methods and results: FNA-ANA from the six ATC patients were cultured in RPMI 1640 and propagated in DMEM. Chemosensitivity was evaluated by inhibiting the proliferation with increasing concentrations of five different chemotherapeutic agents (bleomycin, cisplatin, gemcitabine, etoposide, and carboplatin) or TZD (rosiglitazone). Chemotherapeutic agents significantly inhibited (P<0.0001) FNA-ANA proliferation, such as TZD (P<0.001); etoposide was the most effective in reducing cell growth. Another ANA culture for each patient was obtained from a biopsy specimen; the results for the chemosensitivity tests were similar to those obtained with FNA-ANA. The (V600E)BRAF mutation was observed in two ATC patients; the inhibition of proliferation by drugs was similar in tumors with or without (V600E)BRAF mutation.

Conclusions: Our study demonstrates 1) the possibility to obtain FNA-ANA, and opens the way to the use of FNA-ANA to test the chemosensitivity to different drugs (chemotherapeutic agents or TZD; and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics; and 2) that etoposide is highly effective in reducing ATC cell growth in vitro.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biopsy, Fine-Needle
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Proto-Oncogene Proteins B-raf / genetics
  • Rosiglitazone
  • Thiazolidinediones / therapeutic use*
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf