Expression of Shh signaling pathway factors in gastrointestinal stromal tumor tissues and their associations with clinical pathological factors

Objective: To explore the expression of Shh signaling pathway factors in Gastrointestinal stromal tumor (GIST) tissues and their associations with clinical pathological factors. Methods: 129 GIST patient cases that underwent surgery treatment at the first affiliated hospital of Anhui Medical University from January 2001 to December 2008 and with complete records were collected. The expression of Shh signaling pathway proteins Shh, Ptch, Smo and Gli-1 was assayed using immunohistochemistry methods, and the relation between these protein expression and the tumor site, diameter, mitotic figures, NIH risk classification, reoccurrence and prognosis of GIST was analyzed. Results: The expression rate of these four proteins, Shh, Ptch, Smo and Gli-1, in GIST tissues was 90.5%, 83.3%, 85.7%, and 85.7% respectively; The expression level of Ptch was positively associated with that of Smo, but not with Gli-1; the expression level of Smo was positively associated with that of Gli-1; the expression level of Shh, Ptch, Smo or Gli-1 was not associated with patients’ gender or age, while it was associated with tumor size, mitotic figures, and risk classification. The positive expression rate of Shh, Ptch, Smo and Gli-1 in GISTs with high and median risk according to NIH classification was substantially higher than those with extremely low and low risk, and the difference was significant. The positive expression rate of Shh, Ptch, Smo and Gli-1 was significantly higher in recurrent GIST than non-recurrent GIST. The 1-, 3-, and 5-year survival rates of patients with positive expression of Shh, Ptch, Smo and Gli-1 were markedly lower than those with negative expression. The positive expression of Gli-1 was an independent risk factor of patients’ prognosis. Conclusion: The Shh signaling pathway was present and activated in the GIST tissues. The expression of critical proteins in the Shh signaling pathway was correlated, and they may participate in the origination and development of GIST through ligand-dependent activation. The expression of proteins in the Shh signaling pathway was associated with the reoccurrence and prognosis of GIST, particularly, the expression of Gli-1 protein may be used as an important indicator for predicting reoccurrence.