Recurrent intrathoracic thymomas: Potential prognostic importance of cell-cycle protein expression

Objective: Recurrent intrathoracic thymomas may have an unpredictable behavior. Cell-cycle protein expression has proven useful in predicting outcome in a variety of neoplasms. We investigated its potential prognostic importance in recurrent intrathoracic thymomas. Methods: We reviewed the case histories of 25 consecutive patients operated on between 1987 and 2004 for intrathoracic recurrence (7 mediastinal, 18 nonmediastinal) after radical thymomectomy. Complete resection was performed in 14 patients. In the other 11 patients incomplete resection was followed by chemotherapy and radiotherapy. Expression of cell-cycle proteins (p53, p21, and p27) was assessed by immunohistochemistry in specimens retrieved from both initial and recurrent thymomas. Univariate and multivariate analysis for prognostic factors present at the time of the recurrence was performed. Results: Eight of 14 patients who underwent complete resection had a second recurrence after a mean free interval of 20 +/- 9 months, and a new complete resection was reperformed in 4. After incomplete resection, chemotherapy and radiotherapy allowed total remission in 4 subjects and only 1 of these had a second recurrence. Survival after surgery of the recurrence was negatively influenced by incomplete recurrence resection (P = .03), first disease-free interval less than 24 months (P = .03), high p53 (P = .04), low p21 (P = .02), low p27 (P = .003) expressions, and combination of these proteins (p53 high, p21 low, p27 low expression) (P = .0001). Multivariate analysis selected the triple combination of cell-cycle protein expression as the most significant prognostic variable (P = .02, odds ratio = 11.96, 95% confidence interval = 1.39-102.63). Conclusions: Cell-cycle protein expression, and namely the combination of high p53, low p21, and low p27 expression, may have a potential prognostic importance in recurrent intrathoracic thymomas.