Korean J Pathol.  2013 Apr;47(2):116-123.

Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival

  • 1Department of Hospital Pathology, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Korea. chj0103@catholic.ac.kr
  • 2Department of Surgery, St. Vincent's Hospital, The Catholic University of Korea College of Medicine, Suwon, Korea.
  • 3Department of Hospital Pathology, St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.


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.
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.
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).
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.


Hedgehog proteins; Gli-2 protein; Gli protein; Breast neoplasms
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