|
Since p21WAF1 is under the transactivational control of the p53 gene, downregulation of p21WAF1 may occur either because of loss of function mutations of p53 itself, or because of mutations in the WAF1 gene. Between 35-70% of colorectal cancers demonstrate loss of p21WAF1 expression by immunohistochemistry, and decreased levels are associated with an advanced Duke's stage, liver metastases and poor overall survival. Similarly, loss of p21WAF1 expression occurs in nearly a quarter of gastric adenomas, and 50% of gastric carcinomas, suggesting a role for p21WAF1 in malignant progression. Multivariate analysis in gastric cancers has shown p21WAF1 is an independent predictor of poor overall survival. p21WAF1 expression has been used to predict response to preoperative chemotherapy in esophageal carcinomas, with p21WAF1 positive tumors showing stage for stage better response than negative cases. Loss of p21WAF1 expression has also been observed in tumors outside the gastrointestinal tract, such as in the lung, breast, prostate, ovarian, and endometrial carcinomas; in some of these studies, but not all, loss of p21WAF1 expression has been found to be an independent adverse prognostic factor. Because of the intimate interplay between p53 and p21WAF1, simultaneous evaluation of both proteins has often been found to be a better discriminator of prognosis than any one marker alone. For example, in studies on esophageal, colorectal and urothelial malignancies, tumors with intact p53 and p21WAF1 function have a significantly better course than tumors with abrogation of any one protein; expectedly, cases with abnormal expression of both markers have the poorest outcomes.
Veripath Oncodiagnostics offers p21WAF1 as part of the standard esophagus, stomach and colorectal cancer panels, but it can also be ordered individually. As stated previously, concurrent evaluation of and p53 may offer better information for risk stratification. Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade for p21WAF1 finally reflected in a histoscore on each evaluation. For more information contact Dr Raheela Ashfaq at Veripath OncoDiagnostics at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Koga F et al. Negative p53/positive p21 immunostaining is a predictor of favorable response to chemotherapy in patients with locally advanced bladder cancer. Jpn J Cancer Res 91:416; 2000
2. Ropponen KM et al. p21/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis. Br J Cancer 81:133; 1999
3. Sarkar FH et al. Relationship of p21(WAF1) expression with disease-free survival and biochemical recurrence in prostate adenocarcinomas (PCa). Prostate 40:256; 1999
4. Werness BA et al. Prognostic significance of p53 and p21(waf1/cip1) immunoreactivity in epithelial cancers of the ovary. Gynecol Oncol 75:413; 1999
5. Xiangming C et al. p21 expression is a prognostic factor in patients with p53-negative gastric cancer. Cancer Lett 148:181; 2000
6. Zirbes TK Prognostic impact of p21/waf1/cip1 in colorectal cancer. Int J Cancer 89:14; 2000
|
