Expression of p27 in residual rectal cancer after preoperative chemoradiation predicts long-term outcome Journal Article
| Authors: | Moore, H. G.; Shia, J.; Klimstra, D. S.; Ruo, L.; Mazumdar, M.; Schwartz, G. K.; Minsky, B. D.; Saltz, L.; Guillem, J. G. |
| Article Title: | Expression of p27 in residual rectal cancer after preoperative chemoradiation predicts long-term outcome |
| Abstract: | 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. Published by Lippincott Williams & Wilkins © 2004 The Society of Surgical Oncology, Inc. |
| Keywords: | immunohistochemistry; adult; cancer chemotherapy; cancer survival; controlled study; protein expression; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; cancer surgery; retrospective studies; major clinical study; genetics; cancer recurrence; fluorouracil; advanced cancer; multimodality cancer therapy; adjuvant therapy; cancer radiotherapy; disease free survival; combined modality therapy; neoadjuvant therapy; follow up; lymph node metastasis; antineoplastic agent; ki 67 antigen; cell cycle protein; cell cycle proteins; protein bcl 2; antimetabolites, antineoplastic; antineoplastic combined chemotherapy protocols; tumor markers, biological; enzyme inhibitor; retrospective study; protein p53; tumor marker; prediction; cancer invasion; lymph vessel; tumor suppressor gene; biosynthesis; enzyme inhibitors; cyclin dependent kinase inhibitor 1b; folinic acid; protein p27; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; multivariate analysis; preoperative treatment; kaplan meier method; cyclin d1; tumor suppressor protein; antineoplastic antimetabolite; rectal neoplasms; rectum cancer; rectum tumor; protein p21; chemoradiation; perineum; p27; cyclin-dependent kinase inhibitor; humans; prognosis; human; male; female; article |
| Journal Title: | Annals of Surgical Oncology |
| Volume: | 11 |
| Issue: | 11 |
| ISSN: | 1068-9265 |
| Publisher: | Springer |
| Date Published: | 2004-11-01 |
| Start Page: | 955 |
| End Page: | 961 |
| Language: | English |
| DOI: | 10.1245/aso.2004.03.095 |
| PROVIDER: | scopus |
| PUBMED: | 15525823 |
| DOI/URL: | |
| Notes: | Ann. Surg. Oncol. -- Cited By (since 1996):18 -- Export Date: 16 June 2014 -- CODEN: ASONF -- Source: Scopus |
