Overexpression of Hedgehog signaling molecules and its involvement in triple-negative breast cancer

Department of Pathology, Medical College of Dalian University, Dalian, Liaoning 116622, P.R. China.
Oncology letters (Impact Factor: 1.55). 09/2011; 2(5):995-1001. DOI: 10.3892/ol.2011.357
Source: PubMed


The purpose of this study was to investigate the activation of Hedgehog (Hh) signaling molecules and its involvement in triple-negative breast cancer (TNBC). A total of 123 cases of paraffin blocks, including 83 cases of primary breast carcinoma, 30 cases of mammary hyperplasia and 10 cases of normal breast tissue, were immunohistochemically analyzed for Sonic Hedgehog (SHH), Patched-1 (PTCH1), Smoothened (SMO) and glioma-associated oncogene homoglog 1 (GLI1) expression. The expression of SMO and GLI1 in TNBC was significantly increased in comparison to non-triple-negative breast cancer (nTNBC). GLI1 expression manifested an inverse association with the estrogen receptor. The levels of GLI1 expression were increased in lymph node-positive cases. The expression of SHH and SMO was increased in high histological grades. Furthermore, the expression of SMO and GLI1 was correlated with superior tumor stage. The expression of SHH, SMO and GLI1 was significantly increased in breast cancer and mammary hyperplasia. PTCH1 expression was significantly decreased in breast cancer compared to mammary hyperplasia and normal breast tissue. For the first time, clinical evidence has been provided in support of significant roles of Hh signaling in TNBC. Hh signaling is involved in breast ductal changes and malignant transformation. Measures to inhibit Hh activity may improve the prognosis of TNBC patients.

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    • "Patients with overexpression of glioma-associated oncogene homolog 1 (GLI1) showed a higher rate of lymph node metastasis. Thus, inhibition of Hedgehog genes might improve TNBC prognosis [36]. Patients with negative lymph nodes and TNBC showed an increased level of VEGFC and VEGFD (which demonstrates a clear link between TNBC and lymphangiogenesis) [61] and an overexpression of progranulin/VEGF/CD105 [26]. "
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