Marech Ilaria, Ammendola Michele, Leporini Christian, Patruno Rosa, Luposella Maria, Zizzo Nicola, Passantino Giuseppe, Sacco Rosario, Farooqi Ammad Ahmad, Zuccalà Valeria, Leo Silvana, Dentamaro Rosalba, Porcelli Mariangela, Gadaleta Pietro, De Sarro Giovambattista, Gadaleta Cosmo Damiano, Ranieri Girolamo
Interventional and Medical Oncology Unit, National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy.
Department of Medical and Surgery Science Medical School, Clinical Surgery Unit, Magna Graecia University, 88100 Catanzaro, Italy.
Oncotarget. 2017 Dec 22;9(8):7918-7927. doi: 10.18632/oncotarget.23722. eCollection 2018 Jan 30.
C-Kit protein is a transmembrane tyrosine kinase (TK) receptor (c-KitR-TK), which is predominantly expressed on mast cells (MCs) playing a role in tumor angiogenesis. It could be also expressed on epithelial breast cancer cells (EBCCs), but no data have been published regarding the correlation between mast cells positive to c-KitR (MCs-c-KitR), EBCCs positive to c-KitR (EBCCs-c-KitR), BC angiogenesis in terms of microvessel density (MVD) and the main clinic-pathological features. This study aims to evaluate the above parameters and their correlations in a series of selected 121 female early BC patients. It has been found a strong correlation between MVD and MCDPT, and MCs-c-KitR, MVD and MCs density positive to tryptase (MCDPT), and MCs-c-KitR and MCDPT by Pearson correlation. These data suggest an involvement of both MCDPT and MCs-c-KitR in BC tumor angiogenesis. Furthermore, BC tissue expressing c-KitR could be a putative predictive factor to c-KitR-TK inhibitors. In this way, selected patients with higher MCs-c-KitR could be candidate to receive c-KitR-TK inhibitors (e.g. masitinib, sunitinib) or tryptase inhibitors (e.g. nafamostat mesilate, gabexate mesilate).
C-Kit蛋白是一种跨膜酪氨酸激酶(TK)受体(c-KitR-TK),主要表达于肥大细胞(MCs),在肿瘤血管生成中发挥作用。它也可表达于乳腺上皮癌细胞(EBCCs),但关于c-KitR阳性肥大细胞(MCs-c-KitR)、c-KitR阳性EBCCs(EBCCs-c-KitR)、微血管密度(MVD)方面的乳腺癌血管生成以及主要临床病理特征之间的相关性,尚无数据发表。本研究旨在评估一系列选定的121例女性早期乳腺癌患者的上述参数及其相关性。通过Pearson相关性分析发现,MVD与肥大细胞脱颗粒百分比(MCDPT)、MCs-c-KitR与MVD、MCs-c-KitR与MCDPT之间均存在强相关性。这些数据表明MCDPT和MCs-c-KitR均参与了乳腺癌肿瘤血管生成。此外,表达c-KitR的乳腺癌组织可能是c-KitR-TK抑制剂的一个假定预测因子。这样一来,选定的MCs-c-KitR较高的患者可能是接受c-KitR-TK抑制剂(如马西替尼、舒尼替尼)或色氨酸酶抑制剂(如甲磺酸萘莫司他、甲磺酸加贝酯)的候选者。