P27kip1 expression is associated with tumor response to preoperative chemoradiotherapy in rectal cancer.
BACKGROUND
Our aim was to ascertain whether or not the response to preoperative chemoradiotherapy for rectal cancer is associated with p27kip1 and p53 protein expression.


METHODS
Thirty-eight patients (27 male, 11 female) with a mean age of 59 years (age range 33-87) and stage II-III rectal cancer received preoperative chemoradiotherapy (45-50.4 Gy; 5-FU 350 mg/m2/day and leucovorin 10 mg/m2/day). Thirty-one underwent low anterior resection; seven underwent abdominoperineal excision. Endoscopic tumor biopsies, performed before adjuvant therapy, were evaluated for: histologic type, tumor differentiation, mitotic index, and p27kip1 and p53 protein expression which were immunohistochemically determined. p53 expression was graded as: a) absent or present in < or =10% of tumor cells; b) present in 11-25%; c) present in 26-75%; and d) present in >75% of tumor cells. p27kip1 expression was assessed using both light microscopy (percent of stained cells x10 HPF) and cytometry with an image analysis workstation. Tumor response, ascertained with histology, was classified using a scale from 0 (no response) to 6 (complete pathologic response).


RESULTS
The mitotic index for the endoscopic biopsies was low in 14 cases, moderate in 17 cases, and high in 7 cases. p53 protein expression was found in 21 (a), 3 (b), 3 (c), and 11 (d) cases. The mean percentage of cells expressing the p27kip1 protein was 34 (range 0-77.14%). A close correlation was found between cytometric and light microscopy findings for p27kip1 (r2 = 0.92, P = .0001). Tumor differentiation was good in 5 cases, poor in 2 cases, and moderate in the remaining 31 cases. While the response to adjuvant therapy was good/complete in 25 (65.78%) cases, it was absent/poor in 13 (34.21%) cases. Univariate analysis associated type of adjuvant therapy (chemoradiotherapy, P = .0428) and p27kip1 protein lower expression (P = .0148) with a poor response to adjuvant treatment. Stepwise linear regression found overexpression of p53 and p27kip1 and young age to be independent variables that were linked to a good response to adjuvant therapy.


CONCLUSIONS
Lack of p27kip1 and p53 protein expression in rectal cancer is associated with a poor response to preoperative adjuvant therapy.
Esposito
G
G
Section of Oncology, Department of Oncology and Surgery of the University of Padova, Italy. cmaltese@ux1.unipd.it
Pucciarelli
S
S
Alaggio
R
R
Giacomelli
L
L
Marchiori
E
E
Iaderosa
G A
GA
Friso
M L
ML
Toppan
P
P
Chieco-Bianchi
L
L
Lise
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D003131:Combined Modality Therapy; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D012189:Retrospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins
D000964:Antimetabolites, Antineoplastic; D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002955:Leucovorin; D005472:Fluorouracil