Cell culture in esophageal squamous cell carcinoma and the association with molecular markers

Purpose: We reported previously that the patients in whom cancer cells could be cultured as continuous cell lines had a poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. In this study, to evaluate additional evidence of prognostic significance and the genetic background of cell culture, we analyzed 203 ESCC patients. Experimental Design: Culture samples were obtained from resected 203 primary ESCC (from 1986 to 1998; R0 resection). The expression of six molecular markers was evaluated retrospectively in resected primary esophageal tumors by immunohistochemical analysis, and the capability of establishing cell lines was compared. Results: Thirty-five cell lines (17.2%) were established from 203 ESCC patients: group 1 (n = 35), from whom cancer cells could be cultured as continuous cell lines, and group 2 (n = 168), from whom cell lines could not be established. The cumulative survival rate of patients in group 1 was significantly lower than that of those in group 2 (P = 0.0006). Cox's proportional hazard model revealed that cell culture capability was an independent prognostic factor (risk ratio, 1.98; P = 0.007). Univariate logistic regression analysis revealed that cell culture capability had associations with the following molecular biological factors: cyclin D1, p53, murine double minute 2, p27, and fragile histidine triad gene (P < 0.05). However, multivariate logistic regression analysis revealed that p53 protein accumulation and MDM2 protein expression predict establishment of cell line in ESCC (odds ratio, 7.72 and 8.62, respectively). Conclusions: Cell culture capability is a significant prognostic factor in ESCC. p53 and MDM2 may have a crucial role in the establishment of ESCC cell lines.