gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

The predictive value of genes of the TGFß1 pathway in multimodal treated patients with esophageal squamous cell carcinoma

Meeting Abstract

  • corresponding author presenting/speaker Björn Brücher - Chirurgische Klinik und Poliklinik, TU München, Deutschland
  • F. Pühringer-Oppermann - Institut für Pathologie, TU München
  • Michael Molls - Institut für Strahlentherapie, TU München
  • Jörg-Rüdiger Siewert - Chirurgische Klinik und Poliklinik, TU München
  • Mario Sarbia - Institut für Pathologie, TU München

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP491

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Veröffentlicht: 20. März 2006

© 2006 Brücher et al.
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Purpose: To determine the predictive value of gene expression analysis in patients with esophageal squamous cell carcinoma (ESCC) and neoadjuvant combined radiochemotherapy (RTx/CTx).

Patients and Methods: RNA was prepared from pretherapeutic taken formalin-fixed and paraffin-embedded biopsies of 99patients with histological proven intrathoracic locally advanced ESCC (cT3, cN0/+, cM0) located at or above the level of the tracheal bifurcation, who underwent preoperative combined simultaneous RTx/CTx with consecutive esophagectomy. All tumor biopsies underwent tumor-cell-microdissection, RNA-extraction and real-time TaqMan reverse transcriptase-polymerase chain reaction. RT-PCR-measurements were made by doublet measuring. Quantitative mRNA expression of TGFß1 and its downstream effectors Smad4 and Smad7 was correlated with clinical response according to the WHO, postoperative histopathological response by the percentage of residual tumor cells and survival.

Results: Expression of TGFß1 (mean: 7.8; range: 0.0-25.7 arbitrary units), Smad4 (0.1; 0.0-04) and Smad7 (1.6; 0.4-16.1) varied greatly between cases. Histopathological responder (<10% residual tumor cells) within the specimen showed significantly higher levels of Smad4 expression than nonresponder (>10%) (p=0.0320). TGFß1 and Smad7 did not show a correlation between histopathological and clinical response. Expression of the three genes under analysis showed no impact on overall survival. In contrast, overall survival was significantly correlated with histopathological response (p<0.0001) and to a minor degree also with clinical response (p=0.0254).

Conclusions: Higher levels of Smad4 expression is significantly correlated with histopathological response (<10% residual tumor cells). Analysis of TGFß1 and Smad7 seems to have only limited predictive value for ESCC treated with neoadjuvant RTx/CTx and consecutive esophagectomy.