Nestin表达在人类癌症中普遍但高度可变：一项涉及107种肿瘤类型5,917例癌症的组织芯片研究

Nestin (neuroepithelial stem cell protein) is a class VI intermediate filament protein which is transiently expressed in subsets of precursor cells of the peripheral and the central nervous system, muscle cells and other tissues during development. Upon differentiation, nestin expression becomes replaced by tissue-specific intermediate filament but it can be reinduced in the adult during pathological situations. In cancer, nestin was shown to promote tumor cell proliferation, migration, invasion, and angiogenesis. To determine the prevalence of nestin in cancer, nestin expression was analyzed by immunohistochemistry on tissue microarrays containing 5,917 samples from 107 different tumor types. Nestin positivity occurred in 749 (15.7%) of the 4,775 analyzable tumors, and was considered weak in 8.7%, moderate in 4.3%, and strong in 2.7% of cases. Of 107 tumor entities, 70 (65.4%) showed nestin expression in at least one case, and 22 (20.6%) included at least one case with strong nestin positivity. Highest rates tumors with nestin positivity occurred in pleomorphic adenoma of the parotid gland (100%), gastrointestinal stromal tumor (GIST; 93.8%), metastatic malignant melanoma (75.0%), pheochromocytoma (69.8%), leiomyosarcoma (47.4%), cholangiocarcinoma (40.6%), leiomyoma(40.0%), yolk sac tumor (34.1%), squamous cell carcinoma of the vagina (31.0%), the pharynx (27.3%), vulva (25.6%), anal canal (25.5%), oral cavity (24.7%), penis (19.4%), skin (14.7%), larynx (14.5%), cervix (10.8%), esophagus (9.5%), and the urinary bladder (9.5%), serous carcinoma of the ovary (26.7%), embryonal carcinoma of the testis (26.3%), adenocarcinoma of the cervix (26.1%), endometrioid endometrial carcinoma (22.1%), carcinosarcoma of the uterus(20.8%), pancreatic neuroendocrine tumor (20.7%), muscle-invasive urothelial carcinoma (18.3%), prostatic adenocarcinoma (17.2%), gastric adenocarcinoma of the intestinal type (16.2%), adenocarcinoma of the esophagus(15.1%), urothelial carcinoma of the kidney pelvis (14.3%), and in mucinous carcinoma of the ovary (14.3%). The largest cohort of tumors from one entity included 1,186 evaluable invasive breast cancers of no special type (NST). In these tumors, nestin staining was negative in 94.1%, weak in 3.9%, moderate in 1.3%, and strong in 0.8% of cases. A comparison with tumor phenotype revealed that detectable nestin expression was associated with advanced pT stage (p=0.0103), high grade of malignancy (p<0.0001), absence of estrogen (p=0.0054) and progesterone (p=0.0051) receptor expression as well as with “triple negativity” (p=0.0028). The data from this study provide an overview of nestin expression in human cancer and demonstrate that increased nestin levels can occur in many different tumor entities. At least in breast cancer NST, nestin positivity goes along with increased cancer aggressiveness.