Recurrence after neoadjuvant chemo-
radiotherapy (CRT) followed by surgery is high in patients with
esophageal cancer. No standard second line
therapy is currently available for patients with recurrence. This study aimed to evaluate the expression of chemo-radiosensitive genes after neoadjuvant CRT in
residual tumor cells. Thirteen patients with
esophageal squamous cell carcinoma underwent
5-fluorouracil (5-FU) and
cisplatin (CDDP) based CRT followed by surgery. Total
RNA was successfully obtained from 6
formalin-fixed
paraffin-embedded (FFPE) specimens using
proteinase K digestion and
phenol chloroform extraction. TS and DPD as the
5-FU pathway gene, ERCC1 as the CDDP pathway gene, and EGFR,
VEGF, HIF1a as radioresistant genes were measured using real-time reverse transcription polymerase chain reaction; comparing the
mRNA level of each gene in pre-CRT biopsy with that in post-CRT FFPE specimens. Five patients had less than one-third
residual tumor cells in resected specimens histopathologically; eight had more than two-thirds
residual tumor cells. There were significant increases in TS (p=0.02) and DPD (p=0.01) levels in
residual tumor cells after CRT. Significant decreases in ERCC1 (p=0.03), EGFR (p=0.01),
VEGF (p=0.003) and HIF1a (p=0.003) levels were observed.
5-FU and CDDP based CRT up-regulated
5-FU pathway genes and down-regulated CDDP pathway and radioresistant genes. The expression of chemo-radiosensitive genes was significantly changed in
residual tumor cells after CRT. Gene expression analysis of
residual tumor cells in FFPE specimens may be useful when selecting a second line
chemotherapy regimen for recurrent
esophageal cancer after CRT.