REVIEWp53 and p27 as predictors of clinical outcome for rectal-cancer patients receiving neoadjuvant therapy
Introduction
Neoadjuvant radiation, administered alone or in combination with chemotherapy, has been used to shrink the tumor [1] and achieve complete resectability of the rectal cancer with a sphincter-saving procedure. Other advantages of neoadjuvant radiotherapy include lower total dose of radiation and easier displacement of small bowel from the radiation field. However, the response to radiation varies among individual patients. It is thus imperative to determine the different clinico-pathological factors which may be used to predict the radiosensitivity of each patient that will enable us to understand their clinical outcome.
p53, p21, p27, and Bcl-2 are four important proteins involved in the control of the cell cycle [2], [3], [4], [5], [6], [7]. Their status in the cell cycle has been widely investigated for a variety of cancers including those in the rectum. At this time, there are questions as to whether these markers can be the useful indicators to predict patient responses to neoadjuvant radiotherapy or chemoradiotherapy for rectal cancer. This study examines whether these molecular markers could be used to predict tumor response and also evaluate the relationship between them and overall survival rate, including disease-free survival rate.
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Patients and methods
This is a retrospective study composed of 77 patients treated between January 1998 and June 2002 (Table 1). All patients in the study were: (A) histologically confirmed with diagnosis of adenocarcinoma of the rectum, (B) the inferior margin of the tumor being no farther than 15 cm from the anal verge, (C) without distant metastases, (D) previously not having radiotherapy in pelvic region, and (E) treated with pre-operative radiotherapy with or without simultaneous chemotherapy. The protocol used
Results
The percentage of patients showing DS and FR was, respectively, 50% and 17.7%. For the pre-radiation biopsy specimens, the positive rates for the presence of p53, p21, p27, and Bcl-2 were 63.3%, 16.3%, 32.7%, and 16.6%. On the other hand, for the post-operative specimens, the positive rates increased to 69.4%, 20.4%, 73.5%, and 41.6% (Table 2). With respect to the pre-radiation biopsy specimens for DS patients, no significant difference was observed in positive rate for molecular markers (Table
Discussion
Adjuvant radiotherapy or chemoradiotherapy, administered either prior or subsequent to surgery, prevents tumor regrowth and improves survival rate for selected patients suffering from rectal cancer [10], [11], [12], [13], [14], [15], [16], [17]. Tumor response to radiation therapy is typically quite variable, with complete regression occurring from 4% to 30% of patients and significantly down staging for 30–61% of patients [18], [19], [20]. The response would also appear to vary significantly
Acknowledgments
The authors would like to acknowledge Joeming W. Dung, MD, for his assistance in proofreading and editing the paper with respect to the English language.
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