Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region.
OBJECTIVE
Epidermal growth factor receptor (EGFR) has been associated with radioresistance in solid tumors. Recently a polymorphism in the Sp1 recognition site of the EGFR promoter region was identified. The present study investigated the predictive value of this polymorphism for the outcome of chemoradiation in locally advanced rectal cancer.


METHODS
The study included 77 patients with locally advanced T3 rectal tumors. Treatment consisted of preoperative radiation therapy at a total tumor dose of 65 Gy and concomitant chemotherapy with Uftoral. Blood samples from 63 patients were evaluated for Sp1 -216 G/T polymorphism by polymerase chain reaction analysis. Forty-eight primary tumor biopsies were available for EGFR immunostaining. Patients underwent surgery 8 weeks after treatment. Pathologic response evaluation was performed according to the tumor regression grade (TRG) system.


RESULTS
Forty-nine percent had major response (TRG1-2) and 51% moderate response (TRG 3-4) to chemoradiation. The rates of major response were 34% (10/29) in GG homozygote patients compared with 65% (22/34) in patients with T containing variants (p=0.023). Fifty-eight percent of biopsies were positive for EGFR expression (28/48). The major response rates with regard to EGFR immunostaining were not significantly different. EGFR-positive tumors were found in 83% of the GG homozygote patients compared with 38% of patients with TT or GT variants (p=0.008).


CONCLUSIONS
There was a significant correlation between EGFR Sp1 -216 G/T polymorphism and treatment response to chemoradiation in locally advanced rectal cancer. Further investigations of a second set of patient and other treatment schedules are warranted.
Spindler
Karen-Lise Garm
KL
Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, University of Southern Denmark, Vejle, Denmark. kalgsp@vgs.vejleamt.dk
Nielsen
Jens Nederby
JN
Lindebjerg
Jan
J
Brandslund
Ivan
I
Jakobsen
Anders
A
D000368:Aged; D003131:Combined Modality Therapy / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012004:Rectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016896:Treatment Outcome
D005819:Genetic Markers; D066246:ErbB Receptors