Expression of nestin in cancer: a tissue microarray study involving 13,318 cancers from 148 tumor entities

BACKGROUND: Nestin (neuroepithelial stem cell protein) is a class VI intermediate filament protein which is transiently expressed in subsets of precursor cells of various tissues during development. Nestin expression can be reinduced in the adult during pathological situations. METHODS: To better comprehend the prevalence of nestin in different cancer types, nestin was analyzed by immunohistochemistry on tissue microarrays (TMAs) containing 17,285 samples from 148 different tumor types. Our antibody was validated using a second independent antibody on 76 different normal tissues, ensuring a broad range of proteins to be tested for cross-reactivity. RESULTS: Of 13,318 analyzable tumors, nestin staining was absent in 11,677 (87.7%), weak in 961 (7.2%), moderate in 360 (2.7%), and strong in 320 (2.4%) cases. Of 148 tumor categories, 119 showed nestin staining in at least one case, and 57 included at least one sample with strong positivity. Nestin positivity was most seen in tumors of the salivary glands (up to 100%), gastrointestinal stromal tumors (GIST) (93.8%), tumors of the peripheral nerves (up to 93.8%) and malignant melanomas (81.8%). High nestin expression was linked to high grade (p < 0.0001), estrogen (p = 0.0054), and progesterone receptor negativity (p = 0.0051), as well as a triple negative phenotype (p = 0.0028) in invasive breast cancer NST, in papillary as well as poor ISUP (p=0.0149), Fuhrman (p=0.0006) and Thoenes grades (p=0.0099) in clear cell renal cell carcinoma, invasive tumor growth in urothelial carcinoma of the urinary bladder (pTa vs. pT2-4; p < 0.0001), and advanced pT stage (p = 0.0477) in serous carcinoma of the ovary. CONCLUSIONS: 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. Significant associations with unfavorable tumor characteristics in multiple entities argue for a role of nestin in driving cancer aggressiveness, which may further support the concept of exploring nestin as a drug target.