Biological predictive factors in rectal cancer treated with preoperative radiotherapy or radiochemotherapy.
We analysed the expression of microsatellite instability, p53, p21, vascular endothelial growth factor and thymidylate synthase (TS) in pretreatment biopsy specimens from 57 locally advanced rectal cancers. The aim of the study was to correlate the expression of these markers with pathological response. Nineteen patients were treated with preoperative concomitant radiotherapy (RT) and fluorouracil/oxaliplatin-based chemotherapy (RCT), while 38 had RT alone. Pathological complete remission (pCR) and microfoci residual tumour (micR) occurred more frequently in patients treated with RCT (P=0.002) and in N0 tumours (P=0.004). Among patients treated with RCT, high TS levels were associated with a higher response rate (pCR+micR; P=0.015). No such correlation was found in the RT group. The other molecular factors were of no predictive value. Multivariate analysis confirmed a significant interaction between nodal status and the probability of achieving a pathological response (P=0.023) and between TS expression and treatment, indicating that a high TS level is predictive of a higher pathological response in the RCT subset (P=0.007). This study shows that lymph node status is the most important predictive factor of tumour response to preoperative treatment. Thymidylate synthase expression assessed immunohistochemically from pretreatment tumour biopsies may be a useful predictive marker of rectal tumour response to preoperative RCT.
Negri
F V
FV
U.O. Oncologia Medica, Azienda Ospedaliero-Universitaria di Parma, via Gramsci, Parma 43100, Italy. fnegri@ao.pr.it
Campanini
N
N
Camisa
R
R
Pucci
F
F
Bui
S
S
Ceccon
G
G
Martinelli
R
R
Fumagalli
M
M
Losardo
P L
PL
Crafa
P
P
Bordi
C
C
Cascinu
S
S
Ardizzoni
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017322:Clinical Trials, Phase II as Topic; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D012074:Remission Induction; D013940:Thymidylate Synthase / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D013940:Thymidylate Synthase; D005472:Fluorouracil