High pretherapeutic thymidylate synthetase and MRP-1 protein levels are associated with nonresponse to neoadjuvant chemotherapy in oesophageal adenocarcinoma patients.
BACKGROUND
The aim of this study was to determine whether pretherapeutic protein expression levels of the excision repair cross-complementing (ERCC1) enzyme, thymidylate synthetase (TS), multidrug-resistance protein 1 (MRP-1) and P-glycoprotein (P-gp) are associated with tumour response to cisplatin and fluorouracil (5-FU)-based neoadjuvant chemotherapy in oesophageal adenocarcinomas.


METHODS
The expression levels of ERCC1, TS, MDR-1 and P-gp were determined immunohistochemically in pretherapeutic tumour biopsies from 40 oesophageal adenocarcinoma patients and were correlated with histopathological tumour regression and with patient survival. Protein expression was compared to mRNA data, which was previously published for ERCC1, TS and MRP-1 and newly determined for the purpose of this study for MDR-1/P-gp.


RESULTS
High-TS and -MRP-1 protein expression was correlated with tumour non-response to chemotherapy (P = 0.001 and P = 0.036, respectively). For ERCC-1 and P-gp, no association between pretherapeutic protein expression and response was found. There was no correlation between mRNA levels and protein expression for all investigated markers. Survival analysis revealed a trend towards increased survival for low-ERCC-1 expression (P = 0.079).


CONCLUSIONS
The pattern of pretherapeutic expression of TS and MRP-1 is related to chemotherapy response in oesophageal adenocarcinoma patients. Immunohistochemical assessment of these markers may be helpful for response prediction.
Langer
Rupert
R
Institute of Pathology, Technische Universität München, Munchen, Germany. rupert.langer@lrz.tu-muenchen.de
Ott
Katja
K
Feith
Marcus
M
Lordick
Florian
F
Specht
Katja
K
Becker
Karen
K
Hofler
Heinz
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D005472:Fluorouracil