Expression of epidermal growth factor receptor and proliferating cell nuclear antigen predicts response of esophageal squamous cell carcinoma to chemoradiotherapy.
BACKGROUND
Multimodality therapy with chemotherapy and radiotherapy followed by surgery may improve survival in patients with esophageal squamous cell carcinoma compared with each of the individual treatment options. Histologic assessment of resected tumors after chemoradiotherapy shows that some patients have a complete response with no residual tumor, whereas other patients derive no benefit. The ability to predict response to chemoradiotherapy would allow treatment to be planned accordingly.


METHODS
Expression of the tumor growth and proliferation proteins epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) was determined using immunohistochemical staining of pretreatment endoscopic biopsies from patients with esophageal squamous cell carcinoma who were randomized to chemoradiotherapy before surgery. Response to chemoradiotherapy was assessed by histologic examination of the resected specimens. Response to chemoradiotherapy and survival were correlated with EGFR and PCNA expression individually and with both markers combined as EGFR/PCNA:


RESULTS
Of 14 patients available for study, 6 had a complete histologic response (CR) to chemoradiotherapy with no residual tumor in the resected specimen, 3 had a partial response (PR) to chemoradiotherapy, and the remaining 5 had minimal response (MR). Of the nine patients with a CR or PR, tumors of eight patients were negative for one or both markers. Of the five patients with an MR, four tumors were positive for both EGFR and PCNA (P < 0.05, Fisher's exact test). Comparison of survival from the date of randomization shows that patients with tumors negative for one or both markers had a significant survival advantage (P = 0.0003, log-rank test).


CONCLUSIONS
Evaluation of PCNA and EGFR status of pretreatment biopsies may identify a group of patients likely to derive the greatest benefit from chemoradiotherapy before surgery in terms of histologic response and long term survival.
Hickey
K
K
Department of Surgery, St. James's Hospital, Dublin, Ireland.
Grehan
D
D
Reid
I M
IM
O'Briain
S
S
Walsh
T N
TN
Hennessy
T P
TP
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D066246:ErbB Receptors; D002945:Cisplatin; D005472:Fluorouracil