Pisamai S, Rungsipipat A, Kunnasut N, Suriyaphol G
Biochemistry Unit, Department of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand; Companion Animal Cancer Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
Companion Animal Cancer Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand; Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
J Comp Pathol. 2017 Aug-Oct;157(2-3):150-162. doi: 10.1016/j.jcpa.2017.07.004. Epub 2017 Aug 17.
Feline mammary carcinoma (FMC) is a common cancer with high metastatic potential and high mortality rate. Loss of cell-cell interactions and degradation of the extracellular matrix by proteinases enhances tumour invasion and metastasis. Peripheral neoplastic foci (PNF) are defined as the presence of discrete tumour cell clusters, splitting off from central neoplastic foci (CNF) and lodging around these CNF. PNF therefore locate at the tumour-host interface at the site of invasion. The aim of this study was to evaluate immunohistochemically the expression of cell adhesion molecules (e-cadherin [CDH-1], syndecan 1 [SDC-1] and nectin-2), matrix metalloproteinases (matrix metalloproteinase [MMP]-2, MMP-7 and MMP-9) and their tissue inhibitors (tissue inhibitor of matrix metalloproteinase [TIMP]-1 and TIMP-2) together with the cellular proliferation marker, Ki67, in CNF and PNF of FMCs of different clinical stages and histological grades. Compared with control sections from areas of mammary gland hyperplasia, lower expression of MMP-7 and TIMP-2 was observed in all stages. Increased expression of TIMP-1 was observed in PNF in early-stage disease with no metastasis, while marked expression of CDH-1 and Ki67 occurred in late-stage FMC. In addition, the expression of MMP-2, MMP-9 and TIMP-1 in PNF of tumours with high histological grade (grade III) was higher than in low-grade tumours. The observed divergent protein expression in PNF could potentially form the basis of acting as novel markers in FMC. Potential markers may include the expression of TIMP-1 in PNF in early stage lesions, the expression of CDH-1 and Ki67 in late stages and the expression of MMP-2, MMP-9 and TIMP-1 in high-grade tumours.
猫乳腺肿瘤（FMC）是一种常见癌症，具有高转移潜能和高死亡率。细胞间相互作用的丧失以及蛋白酶对细胞外基质的降解会增强肿瘤的侵袭和转移。外周肿瘤灶（PNF）被定义为存在离散的肿瘤细胞簇，这些细胞簇从中央肿瘤灶（CNF）分离出来并聚集在这些CNF周围。因此，PNF位于肿瘤侵袭部位的肿瘤-宿主界面处。本研究的目的是通过免疫组织化学方法评估不同临床分期和组织学分级的FMC的CNF和PNF中细胞粘附分子（E-钙粘蛋白[CDH-1]、多配体蛋白聚糖1[SDC-1]和连接蛋白2）、基质金属蛋白酶（基质金属蛋白酶[MMP]-2、MMP-7和MMP-9）及其组织抑制剂（基质金属蛋白酶组织抑制剂[TIMP]-1和TIMP-2）的表达，以及细胞增殖标志物Ki67的表达。与乳腺增生区域的对照切片相比，在所有阶段均观察到MMP-7和TIMP-2的表达较低。在无转移的早期疾病的PNF中观察到TIMP-1表达增加，而在晚期FMC中观察到CDH-1和Ki67的显著表达。此外，高组织学分级（III级）肿瘤的PNF中MMP-2、MMP-9和TIMP-1的表达高于低分级肿瘤。在PNF中观察到的不同蛋白表达可能潜在地构成FMC中新型标志物的基础。潜在标志物可能包括早期病变的PNF中TIMP-1的表达、晚期的CDH-1和Ki67的表达以及高分级肿瘤中MMP-2、MMP-9和TIMP-1的表达。
