Expression of Cell Cycle-Regulatory Proteins in Rectal Cancer: Significance of the Tumor Response to Preoperative Radiochemotherapy and for the Prognosis

Yoo, Jinyoung; Shin, Jung Ha; Jung, Ji Han; Choi, Hyun Joo; Kang, Seok Jin; Kang, Chang Suk; Lee, Kyo Young

Abstract

BACKGROUND: Preoperative radiochemotherapy (PRCT) improves the outcomes for patients suffering with locally advanced rectal carcinoma, compared with surgery alone. However, there are no reliable factors predicting the survival and therapeutic benefits.
METHODS
The cell-cycle regulatory proteins were investigated in the pretreatment biopsies from 68 patients who were suffering with rectal cancer by performing immunohistochemical studies of p53, p21, cyclin D1, Rb and p16 protein. The tumor response was graded on a three-scale grading system: no response (NR), partial remission (PR) and complete remission (CR).
RESULTS
The tumors were positive for p53, p21 and cyclin D1 in 46 (67.6%), 32 (47.1%) and 14 (20.6%) cases, respectively. Abnormalities in Rb immunostaining were observed in 9 (13.2%) cases, while an abnormal p16 expression was noted in 59 (86.8%) tumors. Forty-two patients (61.8%) responded to PRCT: 18 (26.5%) cases achieved a CR and 24 (35.3%) cases achieved a PR. None of the above molecular markers were significantly associated with tumor response. However, the altered expression of p16 showed a significant correlation with overall survival (p=0.001). The high expression of p21 demonstrated a trend for longer survival (p=0.061).
CONCLUSIONS
Of the cell-cycle regulatory proteins, p16 may be a valuable marker for to predict rectal cancer patients' survival; however, the role of each cell-cycle regulatory protein for the therapeutic benefits of PRCT needs to be further studied.