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. 2006 Sep 21;12(35):5687-91.
doi: 10.3748/wjg.v12.i35.5687.

Expressions of sonic hedgehog, patched, smoothened and Gli-1 in human intestinal stromal tumors and their correlation with prognosis

Ayumi Yoshizaki  1 , Toshiyuki Nakayama, Shinji Naito, Chun-Yang Wen, Ichiro Sekine
Affiliations

Expressions of sonic hedgehog, patched, smoothened and Gli-1 in human intestinal stromal tumors and their correlation with prognosis

Ayumi Yoshizaki et al. World J Gastroenterol. .

Abstract

Aim: To investigate the role that the hedgehog (Hh) signaling pathway, which includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays in human gastrointestinal stromal tumors (GISTs).

Methods: Surgically resected specimens from patients with GISTs, leiomyomas and schwannomas were examined by immunohistochemical staining for aberrant expression of hedgehog signaling components, Shh, Ptc, Smo and Gli-1, respectively.

Results: In GISTs, 58.1% (18 of 31), 77.4% (24 of 31), 80.6% (25 of 31) and 58.1% (18 of 31) of the specimens stained positive for Shh, Ptc, Smo and Gli-1, respectively. In leiomyomas, 92.3% (12 of 13), 92.3% (12 of 13), 69.2% (9 of 13) and 92.3% (12 of 13) stained positive for Shh, Ptc, Smo and Gli-1, respectively. In schwannomas, 83.3% (5 of 6), 83.3% (5 of 6), 83.3% (5 of 6) and 100% (6 of 6) stained positive for Shh, Ptc, Smo and Gli-1, respectively. Immunohistochemistry revealed that the expressions of Shh and Gli-1 were significantly higher in leiomyomas than in GISTs (P < 0.05, respectively). Shh expression strongly correlated with the grade of tumor risk category and with tumor size (P < 0.05, respectively). However, the expressions of Ptc and Smo did not correlate with histopathological differentiation.

Conclusion: These results suggest that the Hh signaling pathway may play an important role in myogenic differentiation and the malignant potential of human intestinal stromal tumors.

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Figures

Figure 1
Figure 1
Immunohistochemical staining of Hh signaling components. Alkaline phosphatase reaction products demonstrating Shh (A), Ptc (B), Smo (C) and Gli-1 (D) expression. Shh is expressed in the cytoplasm, Ptc and Smo are expressed in both the cytoplasm and cell membrane, and Gli-1 is expressed in both the cytoplasm and nucleus of GIST cells (x 200).
Figure 2
Figure 2
Immunohistochemical staining of human intestinal leiomyomas. Alkaline phosphatase reaction products demonstrating Shh (A), Ptc (B), Smo (C) and Gli-1 (D) expression (x 200).
Figure 3
Figure 3
Immunohistochemical staining of human intestinal schwannomas. Alkaline phosphatase reaction products demonstrating Shh (A), Ptc (B), Smo (C) and Gli-1 (D) expression (x 200).
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