Predictors of response to chemo-radiotherapy and radiotherapy for esophageal squamous cell carcinoma.
BACKGROUND
The sensitivity of tumors to chemotherapy and radiotherapy differs from one case to another and may be influenced by the expression of biological molecules. The presence of six potential predictive markers in esophageal squamous cell carcinoma (ESCC) was investigated and the data obtained were related to the response of the tumors to chemo-radiotherapy and radiotherapy.


METHODS
Biopsy specimens were obtained from 61 patients with ESCC before treatment with chemo-radiotherapy (31 patients) or radiotherapy (30 patients). External radiotherapy was delivered by a two-field technique to a total of 60-70 Gray. Concurrent chemotherapy consisted of cisplatin or nedaplatin and 5-fluorouracil administered intravenously. The patients were examined before and after treatment by endoscopy, esophagography and computed tomography. The clinical response was classified as effective (> 50% decrease in primary lesion), or ineffective. Immunohistochemical staining for p53, p21, bax, bcl2, heat-shock protein (Hsp) 27 and Hsp70 was performed on the biopsy specimens before therapy.


RESULTS
The primary tumor response was effective in 73.8% (45/61) and ineffective in 26.2% (16/61) of patients. Tumors with p53-positive expression were less sensitive than p53-negative tumors (p = 0.033). p21-positive patients (p = 0.027), and Hsp27-negative (p = 0.0057) and Hsp70-negative patients (p = 0.010) were all good responders. Neither bcl2 nor bax expression was related to the efficacy of therapy. Multivariate analysis revealed that Hsp27 was the most reliable predictor of the effect of chemo-radiotherapy and radiotherapy among the four potential markers. p53-negative and Hsp70-negative patients had a more favorable prognosis than p53- and Hsp70-positive patients (p = 0.039, p = 0.038, respectively).


CONCLUSIONS
Expression of Hsp27 was a good predictor of the response of ESCC to chemo-radiotherapy and radiotherapy.
Miyazaki
Tatsuya
T
Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan. tatsuyam@showa.gunma-u.ac.jp
Kato
Hiroyuki
H
Faried
Ahmad
A
Sohda
Makoto
M
Nakajima
Masanobu
M
Fukai
Yasuyuki
Y
Masuda
Norihiro
N
Manda
Ryokuhei
R
Fukuchi
Minoru
M
Ojima
Hitoshi
H
Tsukada
Katsuhiko
K
Kuwano
Hiroyuki
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000208:ethnology* / Q000378:metabolism* / Q000532:radiotherapy; D018797:Cell Cycle Proteins / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C053989:nedaplatin; D002945:Cisplatin; D005472:Fluorouracil