The abnormalities in the p53/p21WAF1 pathway have a significant role in the pathogenesis and progression of gastrointestinal stromal tumors

  • Authors:
    • Yeh-Pin Chou
    • Jui-Wei Lin
    • Chih-Chi Wang
    • Yi-Chun Chiu
    • Chao-Cheng Huang
    • Seng-Kee Chuah
    • Ming-Hong Tai
    • Li-Na Yi
    • Chuan-Mo Lee
    • Chi-Sin Changchien
    • Tsung-Hui Hu
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/or.19.1.49
  • Pages: 49-56
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Abstract

To elucidate the prognostic role and relationship of the p53/p21/PCNA pathway in gastrointestinal stromal tumors (GISTs), a total of 167 resected gastric and small intestinal CD117-positive stromal tumor specimens were collected from January 1987 to December 2000. Immunohistochemical studies were performed on the paraffin sections with antibodies of p53, p21/WAF1, proliferating cell nuclear antigen (PCNA) and Ki-67. The immunoreactivity of four markers was recorded by labeling index (LI, %) for clinicopathologic and survival correlation. The labeling index was 0-83% for p53, 0-81% for p21/WAF1, 0-33% for Ki-67 and 12-92% for PCNA. Completely negative immunostaining (LI<1%) was found in 54.5% of p53, 25.8% of p21/WAF1 and 44.3% of Ki-67. The LI of four markers strongly correlate with each other (p<0.05). Furthermore, the LI of all four markers positively correlate to microscopic tumor mitotic counts (p<0.05). Only the LI of p53 and PCNA positively correlate to tumor sizes. Tumors with non-spindle cell type (versus spindle cell) and high cellular pleomorphism (versus low) exhibited a higher p53, p21/WAF1 and PCNA LI (p<0.05). Increased NIH risk significantly correlates to increased p53, PCNA and Ki-67 (p<0.05) LI. Survival analysis indicated that a large tumor size (≥5 cm, p=0.003), increased tumor mitosis (≥5/50 HPF, p<0.001), high NIH risk (p<0.001), non-spindle cell type (p=0.024), high p53 LI (p<0.001), high p21/WAF1 LI (p=0.007), high Ki-67 LI (p<0.001) and high PCNA LI (p<0.001) were prognostic factors for poor disease-free survival. Independent factors are tumor size, NIH risk, p53 and p21/WAF1 LI. We demonstrated the first evidence of the linear relationship and prognostic role of the p53/p21/PCNA pathway in gastrointestinal stromal tumors. Abnormalities of the p53/p21WAF1 pathway lead to increased proliferating states, thereby triggering the progression of GISTs.

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January 2008
Volume 19 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Chou Y, Lin J, Wang C, Chiu Y, Huang C, Chuah S, Tai M, Yi L, Lee C, Changchien C, Changchien C, et al: The abnormalities in the p53/p21WAF1 pathway have a significant role in the pathogenesis and progression of gastrointestinal stromal tumors. Oncol Rep 19: 49-56, 2008
APA
Chou, Y., Lin, J., Wang, C., Chiu, Y., Huang, C., Chuah, S. ... Hu, T. (2008). The abnormalities in the p53/p21WAF1 pathway have a significant role in the pathogenesis and progression of gastrointestinal stromal tumors. Oncology Reports, 19, 49-56. https://doi.org/10.3892/or.19.1.49
MLA
Chou, Y., Lin, J., Wang, C., Chiu, Y., Huang, C., Chuah, S., Tai, M., Yi, L., Lee, C., Changchien, C., Hu, T."The abnormalities in the p53/p21WAF1 pathway have a significant role in the pathogenesis and progression of gastrointestinal stromal tumors". Oncology Reports 19.1 (2008): 49-56.
Chicago
Chou, Y., Lin, J., Wang, C., Chiu, Y., Huang, C., Chuah, S., Tai, M., Yi, L., Lee, C., Changchien, C., Hu, T."The abnormalities in the p53/p21WAF1 pathway have a significant role in the pathogenesis and progression of gastrointestinal stromal tumors". Oncology Reports 19, no. 1 (2008): 49-56. https://doi.org/10.3892/or.19.1.49