Prognostic value of tumour associated antigen immunoreactivity and apoptosis in cerebral glioblastomas: an analysis of 168 cases.

Korshunov, Andrey; Golanov, Andrey; Sycheva, Regina; Pronin, Igor

doi:10.1136/jcp.52.8.574

Cited by 80 publications

(40 citation statements)

References 42 publications

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“…Two recent papers have found a positive association between apoptotic index and survival Nakamizo et al, 2002). Earlier studies also showed an improved survival with increased apoptosis (Korshunov et al, 1999 andRhodes, 1998) although others have not found such a relationship (Heesters et al, 1999 andNakamura et al, 1997). This inconsistency of results may be related to the variable identity of apoptotic cells, which has not been widely recognized.…”

Section: Discussionmentioning

confidence: 91%

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Walker

Chuah

Rist

et al. 2006

Journal of Neuroimmunology

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We used immunohistochemistry and flow cytometry to assess apoptosis in human glioblastoma multiforme (GBM). Our immunohistochemical study revealed apoptosis of glioma cells expressing glial fibrillary acidic protein and of CD3 + T cells infiltrating GBM. To quantify and phenotype the apoptotic T cells, we performed flow cytometry on lymphocytes separated from GBM. The cells were stained with annexin-V-FLUOS/propidium iodide to identify apoptosis. We found that high proportions of both the CD4 + and CD8 + T cells were apoptotic. In particular, we found that T cells expressing Fas ligand (Fas-L, CD95L) were eight times more vulnerable to apoptosis than those not expressing Fas-L, which suggests that the Tcell apoptosis is induced by overactivation of the T-cell receptor, possibly in the absence of appropriate costimulation. Our results have implications for the design of immunotherapies for GBM.

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Section: Discussionmentioning

confidence: 91%

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Walker

Chuah

Rist

et al. 2006

Journal of Neuroimmunology

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“…31,32 Several molecular markers have been proposed, including LOH of chromosome 10 and the overexpression of EGFR--both of which are correlated with a poor prognosis. [33][34][35] To learn more about the roles of SOX5 antibody responses in GBM patients, we compared the survival of antibody-positive patients with that of antibody-negative patients. Kaplan-Meier plotting showed that the survival of GBM patients with SOX5 IgG was significantly prolonged, compared to that of SOX5 IgG-negative patients.…”

Section: Discussionmentioning

confidence: 99%

Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in glioma patients

Ueda

Yoshida

Kawase

et al. 2007

Intl Journal of Cancer

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We previously reported to identify SOX5 as a glioma antigen by serological screening using a testis cDNA library. The present study was designed to analyze SOX5 expression, its immunoreactivity, and the correlation between SOX5 IgG responses and clinical features in glioma patients to evaluate the possibility of its use as a diagnostic marker. Quantitative RT-PCR and Western blot analysis revealed that SOX5 was expressed in glioma tissues, but not in normal adult tissues, except in the testis. An immunohistochemical analysis showed that SOX5 was expressed in glioma cells, but only a few SOX5-positive cells were detected in non-neoplastic tissues from the cerebral cortex. IgG antibodies against SOX5 were detected in sera from 8 of the 27 glioma patients (27.6%), 0 of the 14 patients with other brain diseases (0%), 1 of the 54 other cancer patients (1.9%) and 1 of the 37 healthy individuals (2.7%). Patients with glioblastoma (GBM) who showed IgG responses against SOX5 exhibited significantly better survival periods than GBM patients without SOX5 antibodies. In summary, SOX5 is aberrantly expressed in glioma and can be recognized as a glioma antigen using IgGs from the sera of glioma patients. Furthermore, there is a statistically significant correlation between the presence of SOX5 IgGs and survival in GBM patients, suggesting that the glioma antigen SOX5 may be useful not only as a diagnostic marker, but also as a prognositic marker in glioma patients. ' 2007 Wiley-Liss, Inc.Key words: glioma; tumor antigen; SOX5; SEREX; IgG response Gliomas are the most common neoplasms of the central nervous system, comprising more than 60% of primary brain tumors. Glioblastoma multiforme (GBM) is the most malignant of these tumors, with an average survival time of less than 16 months and a 5-year survival time of approximately 5%.1 Despite aggressive multimodal therapy, the prognosis for patients with malignant glioma is still poor. Thus, the development of new therapeutic strategies is required.The identification of human tumor antigens is important not only for the analysis of antitumor immune responses and the development of immunotherapy, but also for the development of diagnostic methods.2 Various methods for the identification of tumor antigens have recently been applied, including cDNA expression cloning using tumor-reactive T cells and IgG antibodies in patients' sera as well as a reverse immunology strategy that evaluates the induction of T cells against candidate molecules identified by various techniques, such as systematic gene expression analysis.As of yet, several immunologic markers for glioma patients have been reported.3,4 However, it is unclear how immune responses against these antigens could be induced in glioma patients or whether these immune responses are specific for glioma patients because these antigens were expressed not only in glioma tissue, but also in normal adult tissues. Previously, we reported SOX5 and SOX6 as glioma antigens detected by serological screening using a testis cDNA library and s...

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“…Because patient age is a continuous variable, the cut-off age that subdivided patients best into distinct survival groups was determined according to Korshunov et al 21 Consequently, it was determined that the cut-off age of 40 years was the strongest predictor of outcome (5-year survival rate, 34% for younger patients compared with 6% for older patients; log-rank test; P ϭ 0.0002). We were unable to draw any significant association between the overall survival and other clinical variables, including tumor location (frontal vs. nonfrontal), volume of resection (total/ subtotal vs. partial), and various regimens of chemotherapy.…”

Section: Clinical Variables and Follow-up Datamentioning

confidence: 99%

The prognostic relevance of molecular alterations in glioblastomas for patients age < 50 years

Korshunov

Sycheva

Golanov

2005

Cancer

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BACKGROUNDIn patients with glioblastoma, age < 50 years was identified as a consistent prognostic variable. In addition, the prognosis for these patients may be determined by a complex interaction between age and genetic alterations. The objective of the current study was the molecular analysis of glioblastomas from adult patients age < 50 years (“young adults”).METHODSThe authors analyzed a set of 189 glioblastoma specimens. Fluorescence in situ hybridization was performed with a set of 10 chromosome probes (1p36, 1q25, centomere probe 7 [CEP7], 7p12/epidermal growth factor receptor gene (EGFR), CEP9, 9p21/p16, CEP10, 10q23/phosphatase and tesnin homolog gene (PTEN), 19p13, and 19q13).RESULTSPatient age < 40 years was associated strongly with a favorable prognosis. Patients age ≥ 40 years frequently showed EGFR amplification, loss of 9p, loss of 10q, and gain of chromosome 19. The patients with − 19q were age < 40 years. The survival was shorter for patients with EGFR amplification, gain of chromosome 7, loss of 9p, loss of 10q, and gain of chromosome 19. In contrast, the patients who had tumors with gain of chromosome 9 or loss of 19q had more favorable outcomes. In a multivariate analysis, gain of chromosome 9 (P = 0.026) and loss of 10q23 (P = 0.007) reached the level of independent prognostic value. In addition, the prognostic value of molecular alterations in patients age < 40 years and patients age > 40 years were examined separately. Consequently, EGFR amplification, − 9p, and + 9 were significant for both age groups, whereas gain of chromosome 7 and loss of 10q showed clinical importance only among patients age > 40 years.CONCLUSIONSAdult patients age < 50 years with glioblastoma had molecularly distinct disease, and the age‐dependent heterogeneity seen on the chromosomal level also applied at the clinical level. Cancer 2005. © 2005 American Cancer Society.

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Prognostic value of tumour associated antigen immunoreactivity and apoptosis in cerebral glioblastomas: an analysis of 168 cases.

Cited by 80 publications

References 42 publications

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in glioma patients

The prognostic relevance of molecular alterations in glioblastomas for patients age < 50 years

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