乳腺癌组织中Hedgehog相关蛋白的表达及其临床意义

目的 探讨Hedgehog相关蛋白在乳腺癌中的表达及其临床意义。方法 从334例乳腺癌 组织中制备组织块。免疫组织化学法检测六种Hedgehog信号蛋白（Shh、ptch、Smo、Gli-1、 Gli-2和Gli-3）的表达。结果 Hedgehog信号蛋白表达与一些预后因素显著相关，包括淋巴结转 移与Shh（P=0.001）、Gli-3 (P<0.001)、Ptch(P=0.025)的相关性、分期与Shh和Ptch表达（P分别 为0.007和0.037）的相关性，核分级与Smo(P=0.004)和Gli-3（P=0.026）的相关性，组织学分级与 Smo(P=0.007)的相关性。Shh、Ptch、Smo、Gli-1、Gli-2和Gli-3表达在表型之间差异有统计学意义 （P分别为<0.0001、<0.0001、0.004、0.039、0.031和0.003）。Gli-2表达与较差的整体生存结果相关 （P=0.012）。结论 Hedgehog通路表达激活与乳腺癌的侵袭性相关，可能是乳腺癌的一个有效的治 疗靶点。Gli-2可作为乳腺癌的一个预后指标。

Expression of Hedgehog Related Proteins in Breast Carcinoma and Its Significance

Objective To investigate the expression and clinical significance of Hedgehog related proteins in human primary breast carcinoma. Methods Tissue microarray blocks were prepared from 334 cases of breast carcinoma tissues. Immunohistochemical method was applied to analyze the expression of six Hedgehog signaling proteins, including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene Gli-1, Gli-2, and Gli-3. Results Expression of Hedgehog signaling proteins were significantly correlated with some prognostic factors, including the correlation of lymph node metastasis with the expression of Shh (P=0.001)，Gli-3 (P<0.001) and Ptch(P=0.025), the correlation of staging with Shh and Ptch expression (P=0.007 and P=0.037, respectively), the correlation of nuclear grades with Smo and Gli-3 expression(P=0.004, P=0.026), and the correlation of histologic grades with Smo expression (P=0.007). The expression of Shh, Ptch, Smo, Gli-1, Gli-2 and Gli-3 were significantly different based on phenotypes (P=0.0001, P=0.0001, P=0.004, P=0.039, P=0.031 and P=0.003 respectively). Gli-2 expression was correlated with a worse overall survival (P=0.012). Conclusion The activation of Hedgehog pathway expression is correlated with the invasiveness of breast carcinoma. Hedgehog pathway may be a useful therapeutic target for breast carcinoma. Gli-2 could be a prognostic marker.