Complement activation in astrocytomas: deposition of C4d and patient outcome.

Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Astrocytoma/*immunology ; Brain Neoplasms/*immunology ; Complement Activation/*immunology ; Complement C4b/*immunology ; Peptide Fragments/*immunology; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD34/immunology ; Antigens, CD34/metabolism ; Astrocytoma/metabolism ; Astrocytoma/pathology ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Chi-Square Distribution ; Child ; Complement C4b/metabolism ; Disease Progression ; Glioblastoma/immunology ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Grading ; Peptide Fragments/metabolism ; Prognosis ; Tissue Array Analysis ; Young Adult

Background: C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or patient survival.
Methods: Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with a point counting grid yielding a percent of C4d and CD34 positive area of the sample.
Results: The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016, respectively, Kruskal-Wallis test). However, C4d positive tumor area percentages were higher in grade I pilocytic astrocytomas than in grade II-IV diffusely infiltrating astrocytomas (p = 0.041, Mann-Whitney test). There was a significant correlation between CD34 positive and C4d positive endothelial area fraction in diffusely infiltrating astrocytomas (p < 0.001, Pearson correlation). In these tumors, the increasing intensity of C4d staining was also associated with worsened patient outcome (p = 0.014, log-rank test).
Conclusion: The worsening of patient outcome and malignant progression of tumor cells seem to be connected to microenvironmental changes evoked by chronically activated complement.

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0 (Antigens, CD34)
0 (Peptide Fragments)
80295-50-7 (Complement C4b)
80295-52-9 (complement C4d)

Date Created: 20121204 Date Completed: 20130523 Latest Revision: 20240505

20240505

PMC3517746

10.1186/1471-2407-12-565

23199209