Expression of p27 in residual rectal cancer after preoperative chemoradiation predicts long-term outcome.
BACKGROUND
Compared with surgery alone, preoperative radiotherapy and 5-fluorouracil-based chemotherapy (combined-modality therapy; CMT) improves outcomes in patients with locally advanced rectal cancer. Although numerous studies have focused on identifying molecular markers of prognosis in the primary rectal cancer before CMT, our aim was to identify markers of prognosis in residual rectal cancer after preoperative CMT.


METHODS
Sixty-seven patients with locally advanced (T3-4 and/or N1) rectal cancer were treated with preoperative radiotherapy (median, 5040 cGy) with or without 5-fluorouracil-based chemotherapy. Residual tumor in the resected specimen, available for 52 patients, was analyzed for tumor-node-metastasis stage, lymphovascular and/or perineural invasion, and immunohistochemical expression of p27, p21, p53, Ki-67, retinoblastoma gene, cyclin D1, and bcl-2. Recurrence-free survival (RFS) was determined by the Kaplan-Meier method and compared by the log-rank test.


RESULTS
With a median follow-up of 69 months, the overall 5-year RFS was 74%. RFS was significantly worse for patients with positive p27 expression (P = .005), T3-4 tumors (P = .02), and positive lymph nodes (P = .04) in the irradiated specimen. On multivariate analysis, positive p27 expression remained an independent negative prognostic factor for RFS (P = .04). None of the other proteins was significantly associated with RFS.


CONCLUSIONS
Our results indicate that positive p27 expression in rectal cancer after preoperative chemoradiation is an independent negative predictor of RFS. Expression of p27 in the residual rectal cancer may therefore identify patients with disease likely to be refractory to standard therapy and for whom investigational approaches should be strongly considered.
Moore
Harvey G
HG
Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room C-1077, New York, NY 10021, USA.
Shia
Jinru
J
Klimstra
David S
DS
Ruo
Leyo
L
Mazumdar
Madhu
M
Schwartz
Gary K
GK
Minsky
Bruce D
BD
Saltz
Leonard
L
Guillem
Jose G
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000096:biosynthesis*; D003131:Combined Modality Therapy; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000032:analysis*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000096:biosynthesis*
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005472:Fluorouracil