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PROX1 is a predictor of survival for gliomas WHO grade II.

Elsir T, Qu M, Berntsson SG, Orrego A, Olofsson T, Lindström MS, Nistér M, von Deimling A, Hartmann C, Ribom D, Smits A - Br. J. Cancer (2011)

Bottom Line: The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.Higher PROX1 protein was associated with poor outcome.In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology-Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital, S-17176 Stockholm, Sweden.

ABSTRACT

Background: The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas.

Methods: A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.

Results: Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.

Conclusion: PROX1 is a novel predictor of survival for grade II gliomas.

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Related in: MedlinePlus

PROX1 protein expression in WHO grade II gliomas. Immunohistochemical staining of PROX1 (brown colour) demonstrating the variability in the amount of PROX1 immunopositive cells between the different tumours samples. (A and B) Fibrillary astrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells. (C and D) Gemistocytic astrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells. (E and F) Oligodendroglioma with a relatively high respectively low number of PROX1 expressing tumour cells. (G and H) Oligoastrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells.
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fig1: PROX1 protein expression in WHO grade II gliomas. Immunohistochemical staining of PROX1 (brown colour) demonstrating the variability in the amount of PROX1 immunopositive cells between the different tumours samples. (A and B) Fibrillary astrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells. (C and D) Gemistocytic astrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells. (E and F) Oligodendroglioma with a relatively high respectively low number of PROX1 expressing tumour cells. (G and H) Oligoastrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells.

Mentions: PROX1 was detected in all 116 cases and manifested as a well-defined nuclear staining. There was an evident variability between the numbers of PROX1 immunopositive tumour cells in the different samples (Figure 1). We also found some intra-tumoral variability in distribution of PROX1-positive cells, as well as a minor variation in staining intensity between different tumour cells within the same sample. We counted only clearly positive nuclear stained cells and consequently counted cells in tumour areas with highest number of immunopositive cells. Results of the two independently performed counts showed agreement (i.e., ⩽10% difference in the proportion of positive tumour cells assessed by the two observers) for 89 samples. For 27 cases, the inter-observer variability was >10%. We recounted these samples and grouped them into three categories (<10% positive cells, 10–30% positive cells and >30% positive cells). This way we came to a consensus for all samples.


PROX1 is a predictor of survival for gliomas WHO grade II.

Elsir T, Qu M, Berntsson SG, Orrego A, Olofsson T, Lindström MS, Nistér M, von Deimling A, Hartmann C, Ribom D, Smits A - Br. J. Cancer (2011)

PROX1 protein expression in WHO grade II gliomas. Immunohistochemical staining of PROX1 (brown colour) demonstrating the variability in the amount of PROX1 immunopositive cells between the different tumours samples. (A and B) Fibrillary astrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells. (C and D) Gemistocytic astrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells. (E and F) Oligodendroglioma with a relatively high respectively low number of PROX1 expressing tumour cells. (G and H) Oligoastrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111172&req=5

fig1: PROX1 protein expression in WHO grade II gliomas. Immunohistochemical staining of PROX1 (brown colour) demonstrating the variability in the amount of PROX1 immunopositive cells between the different tumours samples. (A and B) Fibrillary astrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells. (C and D) Gemistocytic astrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells. (E and F) Oligodendroglioma with a relatively high respectively low number of PROX1 expressing tumour cells. (G and H) Oligoastrocytoma with a relatively high respectively low number of PROX1 expressing tumour cells.
Mentions: PROX1 was detected in all 116 cases and manifested as a well-defined nuclear staining. There was an evident variability between the numbers of PROX1 immunopositive tumour cells in the different samples (Figure 1). We also found some intra-tumoral variability in distribution of PROX1-positive cells, as well as a minor variation in staining intensity between different tumour cells within the same sample. We counted only clearly positive nuclear stained cells and consequently counted cells in tumour areas with highest number of immunopositive cells. Results of the two independently performed counts showed agreement (i.e., ⩽10% difference in the proportion of positive tumour cells assessed by the two observers) for 89 samples. For 27 cases, the inter-observer variability was >10%. We recounted these samples and grouped them into three categories (<10% positive cells, 10–30% positive cells and >30% positive cells). This way we came to a consensus for all samples.

Bottom Line: The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.Higher PROX1 protein was associated with poor outcome.In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology-Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital, S-17176 Stockholm, Sweden.

ABSTRACT

Background: The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcription factor that has a critical role in the development of various organs. PROX1 has been ascribed both oncogenic and tumour suppressive functions in human cancers. We have recently shown that PROX1 may act as a diagnostic marker for high-grade gliomas. The aim of this study was to address the prognostic value of PROX1 in grade II gliomas.

Methods: A total of 116 samples were evaluated for the presence of PROX1 protein. The number of immunopositive cells was used as a variable in survival analysis, together with established prognostic factors for this patient group.

Results: Higher PROX1 protein was associated with poor outcome. In the multivariate analysis, PROX1 was identified as an independent factor for survival (P=0.024), together with the presence of mutated isocitrate dehydrogenase 1 R132H protein, and with combined losses of chromosomal arms 1p/19q in oligodendrocytic tumours.

Conclusion: PROX1 is a novel predictor of survival for grade II gliomas.

Show MeSH
Related in: MedlinePlus