Predictive value of Ki67 and p53 in locally advanced rectal cancer: correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy.
OBJECTIVE
To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen.


METHODS
Formalin fixed, paraffin embedded pre-therapeutical tumor biopsies (n = 22) and post-therapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage II/III) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan real-time PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system.


RESULTS
Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a low Ki67 index in the pre-therapeutical tumor biopsies (corr. coef. = 0.46; P < 0.01) as well as in the post-therapeutical resection specimens (corr. coef. = 0.40; P < 0.05). No significant association was found between p53 and TS mRNA expression or tumor regression.


CONCLUSIONS
Ki67 has, like TS, predictive value in rectal cancer patients after neoadjuvant 5-FU based chemoradiotherapy. The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.
Jakob
Christiane
C
Institute for Pathology, University of Technology, Fetscherstr. 74, D-01307 Dresden, Germany. christiane.jakob@uniklinikum-dresden.de.
Liersch
Torsten
T
Meyer
Wolfdietrich
W
Becker
Heinz
H
Baretton
Gustavo-B
GB
Aust
Daniela-E
DE
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D013940:Thymidylate Synthase / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019394:Ki-67 Antigen; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D013940:Thymidylate Synthase; D005472:Fluorouracil