Histopathological features and clinical course of the gastrointestinal stromal tumors.

Background/aims: C-kit expression is a sensitive marker for a specific group of mesenchymal tumors of the gastrointestinal tract, gastrointestinal stromal tumors, the histogenesis and prognosis of which are uncertain.

Methodology: We have investigated the expression of c-kit by immunohistochemical analysis (APAAP method) in 12 out of 13 cases of mesenchymal gastrointestinal neoplasms operated from January 1991 to December 1998, in which the follow-up data were fully available. Furthermore, the c-kit expression was correlated both with the expression of vimentin, CD34 and the mitotic rate, and with the expression of muscle (muscle-specific actin-HHF35 and desmin) or neural (neuron-specific enolase) differentiation markers.

Results: C-kit was expressed in all 12 cases (100%). Two different patterns of expression were observed: cytoplasmic in 7 (58.3%) cases and nuclear in 3 (25%) cases; in 2 (16.7%) cases both cytoplasmic and nuclear immunostaining was detected. Three (60%) out of the five cases showing a nuclear c-kit expression were also neuron-specific enolase positive, whereas none of the cases showing an exclusively cytoplasmic c-kit expression was neuron-specific enolase positive. The correlation between the two patterns of c-kit expression and the follow-up data have shown a trend towards a better prognosis in gastrointestinal stromal tumors with a nuclear c-kit immunostaining and neuron-specific enolase positivity, but the relatively low number of cases does not allow us to draw conclusions. In gastrointestinal stromal tumors the mitotic rate (> 2 x 10 HPF vs. < 2 x 10 HPF) is related with statistically significant differences (P < 0.05) to the 5-year survival (0% vs. 80%, respectively).

Conclusions: These findings, together with the already known c-kit nuclear immunostaining in normal adrenal medullary cells, suggest that a nuclear c-kit expression in gastrointestinal stromal tumors is consistent with a neural differentiation. In this study the mitotic rate has demonstrated a significant influence on the prognosis of gastrointestinal stromal tumors.