Proliferating cell nuclear antigen immunoreactivity and prognosis of gastrointestinal stromal tumors

To determine the prognostic value of proliferating cell nuclear antigen (PCNA) immunoreactivity in gastrointestinal stromal tumors (GISTs), we analyzed 42 GISTs using the PC10 antibody. Thirty-nine GISTs with adequate follow-up were classified as non-aggressive or aggressive based exclusively on clinical behavior; a 2-year minimum follow-up was required for nonaggressive lesions. The percentage of PCNA-positive nuclei (%PCNA(+)) was significantly greater in colorectal GISTs compared with gastric tumors. No significant differences in %PCNA(+) were observed between gastric and small intestinal or small intestinal and colorectal tumors. The %PCNA(+) strongly correlated with mitotic rate, nuclear pleomorphism, and clinical behavior, whereas size and cellularity weakly correlated with %PCNA(+). Thirty-six GISTs could be classified as having low or high risk for aggressive clinical behavior based on a combination of tumor size, mitotic rate, and %PCNA(+). Twelve of 13 low-risk tumors were clinically nonaggressive, whereas 19 of 23 high-risk tumors were clinically aggressive. This correlation with clinical outcome was highly significant (P = 0.00002). Risk analysis by individual anatomical site also strongly correlated with clinical behavior for gastric (P = 0.0023) and small intestinal (P = 0.0056) tumors. There were too few colorectal GISTs with adequate follow-up and PCNA data for site-specific risk analysis. We conclude that tumor size, mitotic rate, and %PCNA(+) can be used as parameters to predict the clinical behavior of GISTs.