title: High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas.
abstract: Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n = 50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p = 0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III).
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Kimmo J
authors: KJ
authors: Hatanpaa
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Tianshen
authors: T
authors: Hu
authors: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Vamsidhara
authors: V
authors: Vemireddy
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Chan
authors: C
authors: Foong
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Jack M
authors: JM
authors: Raisanen
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Dwight
authors: D
authors: Oliver
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Matthew C
authors: MC
authors: Hiemenz
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Dennis K
authors: DK
authors: Burns
authors: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Charles L
authors: CL
authors: White
authors: Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX.
authors: L Anthony
authors: LA
authors: Whitworth
authors: Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Bruce
authors: B
authors: Mickey
authors: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Martha
authors: M
authors: Stegner
authors: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX.|VA North Texas Health Care System, Dallas, TX.
authors: Amyn A
authors: AA
authors: Habib
authors: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Karen
authors: K
authors: Fink
authors: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX.|Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Elizabeth A
authors: EA
authors: Maher
authors: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX.|Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
authors: Robert M
authors: RM
authors: Bachoo
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D064231:Nestin / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C577484:NES protein, human; D064231:Nestin; D012333:RNA, Messenger; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human