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KMID : 0357920130470020116
Korean Journal of Pathology
2013 Volume.47 No. 2 p.116 ~ p.123
Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival
Im So-Young

Choi Hyun-Joo
Yoo Chang-Young
Jung Ji-Han
Jeon Ye-Won
Suh Young-Jin
Kang Chang-Suk
Abstract
Background: The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established. Methods: Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically. Results: The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p= 0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli- 2 expression was correlated with a worse overall survival outcome (p=0.012). Conclusions: Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker.
KEYWORD
Hedgehog proteins, Gli-2 protein, Gli protein, Breast neoplasms
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