Long-term disease-free survival of patients with radically resected thymomas: relevance of cell-cycle protein expression.
BACKGROUND
Despite radical surgical resection, thymomas often recur. The objective of the current retrospective study was to investigate the prognostic relevance of the expression of cell-cycle proteins in these neoplasms to formulate a possible therapeutic surveillance strategy for the prevention of recurrence.


METHODS
The authors retrospectively reviewed the main clinicopathologic factors, including the World Health Organization (WHO) classification, of patients with thymoma who had undergone radical surgical resection. Specimens were studied using immunohistochemistry and the expression of cell-cycle proteins (i.e., p21, p27, and p53) was assessed. Univariate and multivariate analysis of predicting survival prognostic factors were performed.


RESULTS
The authors analyzed 88 patients with thymoma who underwent radical surgical resection at the study institution. According to the Masaoka staging system, 41 patients had Stage I disease, 31 patients had Stage II disease, and 16 patients had Stage III disease. There were 24 tumor recurrences (27.3%), 4 of which were local, 16 of which were distant intrathoracic, and 4 of which were extrathoracic. The second radical resection provided a disease-free survival rate that was similar to the first. Only Masaoka stage (P = 0.001), WHO classification (P=0.001), high expression of p53 (P=0.03), and low expression of p21 (P=0.02) and p27 (P=0.001) were found to be correlated with a reduced disease-free survival. Low p27 expression was found to be the most significant predictive factor of a short disease-free survival (P=0.001), especially when associated with low p21 expression and high p53 expression (P=0.0001).


CONCLUSIONS
Long-term disease-free survival in thymoma patients treated with radical surgical resection was found to be correlated with Masaoka stage, WHO classification, and expression of cell-cycle proteins, with the latter found to be the most significant predictive factor. Functional cooperation between cell-cycle proteins might constitute another level of regulation in tumor growth. More careful surveillance should be adopted whenever there is negative cell-cycle protein expression.
Mineo
Tommaso Claudio
TC
Department of Thoracic Surgery, Tor Vergata University, Rome, Italy.
Ambrogi
Vincenzo
V
Mineo
Davide
D
Baldi
Alfonso
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D013945:Thymoma / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D013953:Thymus Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D013997:Time Factors
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins