title: Comparative analysis of annexin-1 in neuroepithelial tumors shows altered expression with the grade of malignancy but is not associated with survival.
abstract: In various types of cancer, the expression of members of the annexin family of calcium- and phospholipid-binding anti-inflammatory proteins is dysregulated. Annexin-1 (ANXA1, lipocortin-1) is involved in proliferation, differentiation and apoptosis. It serves as a substrate for the epidermal growth factor receptor (EGFR), which is frequently amplified in primary gliomas. It is unclear how annexin-1 is expressed in various neuroepithelial tumors, and whether there is any association with tumor malignancy or survival. We studied annexin-1 expression in 394 glial neoplasms of all grades of malignancy and 81 normal brain samples by immunohistochemistry using tissue microarrays. The results were validated using western blot and reverse transcription-PCR (RT-PCR). In the normal human brain, the expression of annexin-1 is limited to ependymal cells and subependymal astrocytes, but is also upregulated in reactive astrocytes. Ependymomas and astrocytomas showed significantly higher mean annexin-1 expression levels in the cytoplasm compared with oligodendrogliomas (both: P<0.0001). In addition, nuclear staining of annexin-1 in oligodendroglial tumor cells was significantly reduced (P=0.0002), which may be used as a diagnostic tool for differentiating between astrocytomas and oligodendrogliomas. Although annexin-1 expression in ependymomas decreased with the grade of malignancy, diffuse astrocytomas showed a significant increase in cytoplasmic annexin-1-positive tumor cells. However, survival analysis showed that the expression of annexin-1 is not associated with patient survival. Similar to the EGFR amplification profile, primary glioblastomas had a higher annexin-1 expression level compared with secondary glioblastomas. Thus, annexin-1 upregulation in astrocytomas may contribute to tumor progression and its expression profile is similar to its substrate, EGFR, suggesting a possible regulation thereof.
authors.affiliation: Institute of Brain Research, University of Tuebingen, Tuebingen, Germany. jens.schittenhelm@med.uni-tuebingen.de
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
authors.forename: Katrin
authors.initials: K
authors.lastname: Trautmann
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Tabatabai
authors.forename: Caroline
authors.initials: C
authors.lastname: Hermann
authors.forename: Richard
authors.initials: R
authors.lastname: Meyermann
authors.forename: Rudi
authors.initials: R
authors.lastname: Beschorner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017305:Annexin A1 / Q000032:analysis* / Q000235:genetics; D001254:Astrocytoma / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009837:Oligodendroglioma / Q000737:chemistry; D011379:Prognosis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D013997:Time Factors; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D017305:Annexin A1; D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors