Yoshizaki Ayumi, Nakayama Toshiyuki, Naito Shinji, Wen Chun-Yang, Sekine Ichiro
Department of Molecular Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
World J Gastroenterol. 2006 Sep 21;12(35):5687-91. doi: 10.3748/wjg.v12.i35.5687.
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).
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.
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.
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.
研究包含音猬因子(Shh)、patched(Ptc)、 smoothened(Smo)和Gli-1的刺猬(Hh)信号通路在人类胃肠道间质瘤(GISTs)中的作用。
分别通过免疫组织化学染色检测GISTs、平滑肌瘤和神经鞘瘤患者手术切除标本中刺猬信号通路成分Shh、Ptc、Smo和Gli-1的异常表达。
在GISTs中,分别有58.1%(31例中的18例)、77.4%(31例中的24例)、80.6%(31例中的25例)和58.1%(31例中的18例)的标本Shh、Ptc、Smo和Gli-1染色呈阳性。在平滑肌瘤中,分别有92.3%(13例中的12例)、92.3%(13例中的12例)、69.2%(13例中的9例)和92.3%(13例中的12例)的标本Shh、Ptc、Smo和Gli-1染色呈阳性。在神经鞘瘤中,分别有83.3%(6例中的5例)、83.3%(6例中的5例)、83.3%(6例中的5例)和100%(6例中的6例)的标本Shh、Ptc、Smo和Gli-1染色呈阳性。免疫组织化学显示,平滑肌瘤中Shh和Gli-1的表达显著高于GISTs(P均<0.05)。Shh表达与肿瘤风险分级和肿瘤大小密切相关(P均<0.05)。然而,Ptc和Smo的表达与组织病理学分化无关。
这些结果表明,Hh信号通路可能在人类肠道间质瘤的肌源性分化和恶性潜能中发挥重要作用。