P27 does not predict histopathological response to radiochemotherapy in rectal cancer.
BACKGROUND
Tumor response to radiochemotherapy (RCT) varies considerably, even among patients treated in accordance with the same protocol. The aim of the present study was to test the predictive value of the cell-cycle inhibitor p27kip1 with regard to neoadjuvant RCT response in rectal cancer.


METHODS
P27kip1 was evaluated by immunohistochemistry in pretreatment biopsy material obtained from 42 patients with rectal cancer treated uniformly in accordance with an identical prospective neoadjuvant RCT protocol (CAO/AIO/ARO-94). Four expression patterns (staining intensity [-,+,++,+++] and the percentage of positive cells, evaluated separately for nuclei and cytoplasm) of p27kip1 were investigated for correlation with tumor response, which was assessed in the resected surgical specimen using a histopathological five-point grading system. Additionally, p27(kip1) expression was investigated for correlation with several pathological features, overall survival, and disease-free survival.


RESULTS
p27kip1 expression was as follows: nuclear intensity: -: 8, +: 19, ++: 11, +++: 4 cases, median percentage of positive cells: 18.75%; cytoplasmic intensity: -: 0, +: 25, ++: 12, +++: 3 cases, median percentage of positive cells: 70%. Histopathological tumor regression was acceptable in 30 patients (3 complete; 27 good) and inadequate in 12 patients (7 moderate; 5 minimal). No tumor failed to show some regression. No significant correlation was found between any of the p27kip1 expression patterns and RCT response, tumor differentiation (low grade versus high grade), cT- and ypT-category, UICC stage, overall survival, and disease-free survival.


CONCLUSIONS
p27kip1 cannot aid the individualization of multimodal treatment strategies in rectal cancer, nor can it serve as a predictor of survival.
Günther
Klaus
K
Institute of Pathology, University of Erlangen, Erlangen, Germany. klaus.guenther@rzmail.uni-erlangen.de
Dimmler
Arno
A
Rödel
Franz
F
Reulbach
Udo
U
Merkel
Susanne
S
Bittorf
Birgit R
BR
Matzel
Klaus E
KE
Papadopoulos
Thomas
T
Hohenberger
Werner
W
Sauer
Rolf
R
Rödel
Claus
C
D000230:Adenocarcinoma / Q000378:metabolism* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D003082:Colectomy / Q000379:methods; D003131:Combined Modality Therapy; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018714:Radiotherapy, Adjuvant / Q000379:methods; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000628:therapy*; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D005472:Fluorouracil