Planeix François, Siraj Mohammad-Ahsan, Bidard François-Clément, Robin Blaise, Pichon Christophe, Sastre-Garau Xavier, Antoine Martine, Ghinea Nicolae
INSERM "Tumoral Angiogenesis" Laboratory, Curie Institute, Research Center, Translational Research Department, 26 rue d'Ulm, Paris, France.
Curie Hospital, Oncology Department, 26 rue d'Ulm, Paris, France.
J Exp Clin Cancer Res. 2015 Feb 5;34(1):12. doi: 10.1186/s13046-015-0128-7.
Follicle-stimulating hormone receptor (FSHR) is expressed on the endothelial surface of blood vessels associated with solid tumor periphery, where angiogenesis is known to occur. The correlation between FSHR expression and formation of new peritumoral vessels has not been previously investigated.
We used immunohistochemical techniques involving specific antibodies to detect FSHR and the endothelial markers (CD34, VEGFR2, and D2-40) in tissue samples from 83 patients with lymph node-negative, invasive breast cancer representing four main clinical treatment groups: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple-negative.
The FSHR+ vessels were exclusively located at breast cancer periphery, in a layer that extended 2 mm into and 5 mm outside of the tumor. The percentage of blood vessels expressing FSHR reached a maximum of 100% at the demarcation line between the tumor and the normal tissue. Common among FSHR+ vessels, regardless of breast cancer type, were the high densities of arterioles and venules (6.4 ± 1.4 and 13.9 ± 2.1 vessels/mm(2), respectively). These values were 3-fold higher that those noticed for CD34+ arterioles and venules associated with normal breast tissue located at a distance greater than 10 mm outside the tumors. The average density of FSHR+ and CD34+ blood vessels as well as of D2-40+ lymphatic vessels did not differ significantly among breast cancer subgroups. FSHR+ vessels did not express VEGFR2. The endothelial FSHR expression correlated significantly with the peritumoral CD34+ vessels' density (p < 0.001) and tumor size (p = 0.01).
Endothelial FSHR expression in breast cancer is associated with vascular remodeling at tumor periphery.
促卵泡激素受体（FSHR）表达于实体瘤周边血管的内皮表面，已知此处会发生血管生成。此前尚未研究FSHR表达与肿瘤周围新血管形成之间的相关性。
我们采用免疫组织化学技术，使用特异性抗体检测83例淋巴结阴性浸润性乳腺癌患者组织样本中的FSHR以及内皮标志物（CD34、VEGFR2和D2-40），这些患者代表四个主要临床治疗组：HR+/HER2-、HR+/HER2+、HR-/HER2+和三阴性。
FSHR+血管仅位于乳腺癌周边，在肿瘤内部延伸2毫米和外部延伸5毫米的一层中。在肿瘤与正常组织的分界线上，表达FSHR的血管百分比最高可达100%。无论乳腺癌类型如何，FSHR+血管的共同特征是小动脉和小静脉密度高（分别为6.4±1.4和13.9±2.1条血管/mm²）。这些值比与肿瘤外距离大于10毫米处的正常乳腺组织相关的CD34+小动脉和小静脉的值高3倍。乳腺癌亚组之间FSHR+和CD34+血管以及D2-40+淋巴管的平均密度无显著差异。FSHR+血管不表达VEGFR2。内皮FSHR表达与肿瘤周围CD34+血管密度（p<0.001）和肿瘤大小（p=0.01）显著相关。
乳腺癌中的内皮FSHR表达与肿瘤周边的血管重塑有关。
