mRNA expression of platelet-derived growth factor receptor-beta and C-KIT: correlation with pathologic response to cetuximab-based chemoradiotherapy in patients with rectal cancer.
OBJECTIVE
Deviant expression of platelet-derived growth factor receptor-beta (PDGFRbeta) and c-kit was shown in patients with colorectal cancer. In the present study, mRNA expression of PDGFRbeta and c-kit in 33 patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy with cetuximab/capecitabine/irinotecan in correlation with the tumor regression rate was investigated.


METHODS
Pretherapeutic biopsy cores and tumor material from the resected specimens were collected in parallel with normal rectal mucosa. The expression levels of PDGFRbeta and c-kit were measured by quantitative polymerase chain reaction. Tumors were classified as good responders (tumor regression grade [TRG], 2-3) or poor responders (TRG, 0-1).


RESULTS
The TRG evaluation of the resected specimen was TRG 0-1 in 11 and TRG 2-3 in 22. The median normalized ratios in the pretreatment mucosa vs. tumor biopsy cores was as follows: PDGFRbeta ratio of 15.2 vs. 49.5 (p <0.0001) and c-kit ratio of 0.94 vs. 0.67 (p = 0.014). The same tendency was observed for the median PDGFRbeta ratios after chemoradiotherapy completion: 34.2 vs. 170.0 (p <0.0001). The PDGFRbeta and c-kit mRNA expression values in the pretreatment tumor biopsy cores were lower than the values in the resected specimens: PDGFRbeta ratio 49.5 vs. 170.0 (p = 0.0002) and c-kit ratio 0.67 vs. 1.1 (p = 0.0003). Nevertheless, no correlation was seen between the pretherapeutic PDGFRbeta and c-kit mRNA expression and the pathologic regression rate.


CONCLUSIONS
Cetuximab-based chemoradiotherapy increased PDGFRbeta levels even further compared with the pretreatment samples and deserves further investigation.
Erben
Philipp
P
III. Medizinische Klinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
Horisberger
Karoline
K
Muessle
Benjamin
B
Müller
Martin Christian
MC
Treschl
Anne
A
Ernst
Thomas
T
Kähler
Georg
G
Ströbel
Philipp
P
Wenz
Frederik
F
Kienle
Peter
P
Post
Stefan
S
Hochhaus
Andreas
A
Willeke
Frank
F
Hofheinz
Ralf-Dieter
RD
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics; D003131:Combined Modality Therapy; D017931:DNA Primers; D015342:DNA Probes; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D017931:DNA Primers; D015342:DNA Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta; D000068818:Cetuximab