43 - Freie Mitteilung
16. Mai 2019, 08:30 - 10:00, Szenario 1, 5. OG
Nestin and CD34 expression in colorectal cancer promotes a favorable immune response and consequently a beneficial overall survival
A. Tampakis1, B. Weixler2, S. Rast1, E. C. Tampaki3, E. Cremonesi1, N. Tosti1, C. Kettelhack1, C. Ng1, S. Piscuoglio1, T. Delko1, S. D. Soysal1, G. C. Spagnoli1, U. von Holzen4, S. Eppenberger-Castori1, L. Terracciano1, L. Tornillo1, M. von Flüe1, S. Däster1, R.A. Droeser1, Presenter: A. Tampakis1 (1Basel, 2Berlin/DE, 3Athens/GR, 4Goshen/USA)
Nestin, represents a class VI intermediate filament protein of the cytoskeleton and cells expressing nestin harbor properties of progenitor/stem cells. CD34 is a transmembrane phosphoglycoprotein, known as a marker of hematopoietic progenitor and stem cells. Both molecules have been implicated in processes such as tissue injury and malignant transformation. In colorectal cancer (CRC) they have been used as neoangiogenesis markers. The aim of this study was to evaluate expression patterns of nestin and CD34 in CRC and to determine their clinical significance.
A clinically annotated tissue microarray including 599 patients with CRC was analyzed by immunohistochemistry to investigate expression patterns of nestin and CD34. Results were correlated with clinicopathological characteristics and survival data. Nestin and CD34 gene expression was analyzed in 39 freshly excised CRC specimens via RT-PCR (reverse transcription PCR). Associations of nestin and CD34 with a panel of cytokines and chemokines related to hypoxia and immune response processes were assesed by RT-PCR and TCGA analysis.
Expression of nestin and CD34 was observed only in cells of the tumor stroma. High expression of both markers was correlated with T1 and T2 tumors (p=0.020) as well as with lower vascular invasion (p<0.001). Patients displaying simultaneously high expression of nestin and CD34 demonstrated a beneficial 5-year overall survival (65%; 95%CI=55-73 vs 45% 95%CI=37-53) independent of other clinicopathological characteristics (HR: 0.67; 95%CI=0.46-0.96; p=0.031). After performing RT-PCR nestin and CD34 presented a moderate to strong correlation (r=0.37-0.78, p<0.02) for the following markers; HIF-1α, CD4, CD8, FOXP3, IRF1, GATA3, CCL2, CCL3, CXCL12 and CCL21. Nevertheless, TCGA analysis demonstrated up-regulation of only CCL21, CD4, CXCL12 and FOXP3 when combined expression of both markers exists.
Nestin and CD34 expression in colorectal cancer promotes a favorable immune response and predicts independently a beneficial overall survival