Deregulated p21(WAF1) overexpression impacts survival of surgically resected esophageal squamous cell carcinoma patients.
BACKGROUND
Prognostic effects of cell cycle regulation associated tumor suppressor genes for esophageal squamous cell carcinoma patients are controversial. Clarifying the effects of these genes is beneficial for optimizing patient's outcome.


METHODS
Forty esophageal squamous cell carcinoma patients were included in the study. Tissue samples were analyzed for cell proliferation, DNA content, mutation of p53 gene, and expression of p21 and p53 proteins. Prognostic effects of these parameters were assessed by multivariate analysis.


RESULTS
Seventy-five percent of tumors exhibited aneuploid DNA content. Significantly higher S-phase fractions were detected in tumor samples (p < 0.001). The p53 gene mutated in 52.5% (21 of 40) of tumor samples, p53 immunostaining was detected in 62.5% (25 of 40) of tumor tissues and 50% of tumors over expressed p21. Overexpression of p21 protein did not correlate with p53 gene status, but significantly correlated with abnormal DNA content (p = 0.028). Advanced pTNM stage, lymph node metastasis and p21 overexpression conferred survival disadvantages in univariate analysis (p = 0.013, 0.045 and 0.017, respectively). A Cox multivariable analysis revealed pTNM stage (IIB/III/IV vs. I/IIA; p = 0.024) associated with p21 overexpression (positive vs. negative; p = 0.035) as independent prognostic factors in esophageal squamous cell carcinomas. Surprisingly, p21 overexpression significantly compromised the survival of patients with mutated p53 gene (p = 0.035). However, no significant dismal effect of p21 overexpression can be seen in patients with wild-type p53 gene (p = 0.175).


CONCLUSIONS
Overexpression of p21 correlates with chromosomal instability and serves as an adverse prognostic predictor for patients with esophageal squamous cell carcinoma. Its adverse effect is more prominent when the p53 gene is mutated.
Goan
Yih-Gang
YG
Division of Thoracic Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.
Hsu
Hon-Ki
HK
Chang
Huang-Chou
HC
Chou
Yi-Ping
YP
Chiang
Ke-Hsin
KH
Cheng
Jiin-Tsuey
JT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary / Q000601:surgery*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D016158:Genes, p53 / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005819:Genetic Markers