The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus.
Pretherapeutic identification of oesophageal squamous cell carcinomas that will respond to neoadjuvant chemoradiotherapy is an important attempt for improvement of patient's prognosis. In the current study, pretherapeutic biopsies from 94 oesophageal squamous cell carcinomas (cT3, cN0/+, cM0) in patients who underwent neoadjuvant chemoradiotherapy (RCTx: 45 Gy plus cisplatin and 5-fluorouracil) and subsequent oesophagectomy in the setting of a single-centre prospective treatment trial were investigated by means of immunohistochemistry. Expression of proteins involved in DNA repair and/or cell-cycle regulation, that is p53, p53 (phosphorylated at Ser15), EGFR, ATM protein kinase (phosphorylated at Ser1981) and checkpoint kinase 2 (CHK2) (phosphorylated at Thr68) was correlated with the response to RCTx and with overall survival. Tumours that were positive for CHK2 expression more frequently showed clinically determined regression after RCTx (69.4%) than tumours that were negative for CHK2 expression (32.1%; P=0.0011), whereas other parameters did not correlate with tumour regression. Expression of ATM correlated with expression of CHK2 (P=0.0061) and p53-phospho (P=0.0064). Expression of p53 correlated with expression of p53-phospho (P<0.0001). In contrast to clinical and histopathological response evaluation, none of the molecular parameters under investigation correlated with overall survival. In conclusion, expression analysis of p53, EGFR CHK2 and ATM has no predictive value in multimodally treated oesophageal squamous cell carcinoma.
Sarbia
M
M
Department of Pathology, Unfallkrankenhaus Berlin, Berlin, Germany. 2geka-1@po.cc.yamaguchi-u.ac.jp
Ott
N
N
Pühringer-Oppermann
F
F
Brücher
B L D M
BL
D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000096:biosynthesis; D064447:Checkpoint Kinase 2; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D018450:Disease Progression; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000096:biosynthesis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; D066246:ErbB Receptors; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin; D005472:Fluorouracil