EXPRESSION OF P21(WAF1) PREDICTS OUTCOME OF ESOPHAGEAL CANCER-PATIENTS TREATED BY SURGERY ALONE OR BY COMBINED THERAPY MODALITIES

The p21(WAFI) protein is an important regulator of the cell cycle. Its expression and prognostic significance were investigated immunohistoc hemically in samples of normal esophageal squamous epithelium (n = 10) , severe squamous cell dysplasia (rt = 20), carcinoma in situ (n = 14) , permanent esophageal squamous cell carcinoma cell lines (n = 3), and invasive squamous cell carcinomas treated either by potentially curat ive resection (n = 172) or by combined modality therapy (radiochemothe rapy +/- surgery; n = 38), Whereas p21(WAF1) expression in the normal epithelium was restricted to a few cells adjacent to the basal cell la yer, p21(WAF1) overexpression was frequently found in preneoplasias an d invasive carcinomas. Expression of p21(WAF1) in invasive carcinomas was not correlated with tumor differentiation, pT category, or pN cate gory. Among carcinomas treated by potential curative resection, univar iate (P = 0.0025) and multivariate (P = 0.0081) survival analysis show ed significant correlation of strong p21(WAF1) expression (greater tha n or equal to 50% p21(WAF1)-positive tumor cells) with poor overall su rvival. Univariate survival analysis (P = 0.0006) revealed the same pr ognostic influence in the group of patients treated by combined modali ty therapy. We conclude that overexpression of p21(WAF1) protein is a frequent event in preneoplasias and neoplasias of the esophagus, Immun ohistochemical examination of p21(WAF1) expression may provide importa nt prognostic information for decision-making in the treatment of pati ents with esophageal cancer.