High expression of Sonic Hedgehog signaling pathway genes indicates a risk of recurrence of breast carcinoma

Abstract

Kuo-Shyang Jeng,1 I-Shyan Sheen,2 Wen-Juei Jeng,2 Ming-Che Yu,3 Hsin-I Hsiau,3 Fang-Yu Chang31Department of Surgery, Far Eastern Memorial Hospital, Taipei, 2Department of Internal Medicine, Chang-Gung Memorial Hospital, Linkou Medical Center, Chang-Gung University, Tao-Yuan, 3Department of Medical Research, Far Eastern Memorial Hospital, Taipei, TaiwanBackground: Abnormal activation of the Sonic Hedgehog (SHH) signaling pathway contributing to carcinogenesis of some organs has been reported in the literature. We hypothesize that activation of the SHH pathway contributes to the recurrence of breast carcinoma.Methods: Fifty consecutive patients with invasive breast carcinoma following curative resection were enrolled in this prospective study. The ratios of messenger RNA (mRNA) expression for Sonic Hedgehog (SHH), patched homolog-1 (PTCH-1), glioma-associated oncogene-1 (GLI-1), and smoothened (SMOH) were measured between breast carcinoma tissue and paired noncancerous breast tissue. These ratios were compared with their clinicopathologic characteristics. These factors and the mRNA ratios were compared between patients with recurrence and those without recurrence.Results: The size of the invasive cancer correlated significantly with the ratio of SHH mRNA (P=0.001), that of PTCH-1 mRNA (P=0.005), and that of SMOH mRNA (P=0.021). Lymph node involvement correlated significantly with the ratio of SMOH mRNA (P=0.041). The correlation between Her-2 neu and the ratio of GLI-1 mRNA was statistically significant (P=0.012). Each ratio of mRNA of SHH, PTCH-1, GLI-1, and SMOH correlated significantly with cancer recurrence (P<0.001 for each).Conclusion: We suggest that high expression of SHH mRNA, PTCH-1 mRNA, GLI-1 mRNA, and SMOH mRNA in breast cancer tissue correlates with invasiveness and is a potential biomarker to predict postoperative recurrence.Keywords: SHH pathway, breast carcinoma, prediction, recurrence