Correlation of histopathological features and proliferative potential of gliomas

Germano, Isabelle M.; Ito, Masami; Cho, Kyung G.; Hoshino, Takao; Davis, Richard L.; Wilson, Charles B.

doi:10.3171/jns.1989.70.5.0701

Cited by 54 publications

(16 citation statements)

References 29 publications

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“…We believe that in vitro BrdU labeling is an attractive technique, considering the potential hazards of in vivo labeling. 7 15 however, reported no correlation between the BrdU LI and mitotic index in brain tumors. On the other hand, our results showed an inverse correlation between the BrdU LI and patient age (r =.539), with the tumors found in the younger patients having a higher BrdU LI than the tumors in the older patients.…”

Section: Labeling Index In Normal Tissue and Squamousmentioning

confidence: 91%

Cell Kinetics Study of Upper Aerodigestive Tract Squamous Cell Carcinoma Using Bromodeoxyuridine

Hirano¹,

Zitsch²,

Gluckman³

1993

Ann Otol Rhinol Laryngol

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Thirty patients treated for squamous cell carcinoma of the upper aerodigestive tract were reviewed for a cell kinetics study using bromodeoxyuridine (BrdU). Fresh specimens were obtained from the primary site of the tumors and incubated in Dulbecco's modified Eagle's medium containing BrdU to label S-phase tumor cells. The tumor specimens were stained immunohistochemically with monoclonal antibody against BrdU. The results demonstrated that the BrdU labeling index (BrdU LI) in these cases (470.3 +/- 118.2) was greater than the BrdU LI in normal mucosa (162 +/- 52.4). In a comparison of the clinical data and histopathologic features, the BrdU LI showed an inverse correlation with patient age (r = -.558; p < .01) and a direct correlation with the frequency of mitoses (r = .411; p < .05). Although the significance of the BrdU LI as a prognostic factor cannot be determined at present, this technique provides a simple in vitro test that avoids the potential hazards of in vivo labeling or the use of radioactive materials.

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Section: Labeling Index In Normal Tissue and Squamousmentioning

confidence: 91%

Cell Kinetics Study of Upper Aerodigestive Tract Squamous Cell Carcinoma Using Bromodeoxyuridine

Hirano¹,

Zitsch²,

Gluckman³

1993

Ann Otol Rhinol Laryngol

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“…However, brain tumors of low and intermediate grade contain so few mitoses that an accurate mitotic index is impossible in biopsy specimens. Even in mitotically active tumors, the mitotic index is not necessarily a reliable indicator of the entire pool of proliferating cells because of individual variations in length of the various cell cycle phases (Germano et al 1989). Nuclear IHC markers of proliferation provide alternative assessments of proliferation capacity.…”

Section: Immunohistochemistry Of Nuclear Markersmentioning

confidence: 99%

Insights About Brain Tumors Gained Through Immunohistochemistry and in Situ Hybridization of Nuclear and Phenotypic Markers

McKeever

1998

J Histochem Cytochem.

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Immunohistochemistry (IHC) has provided major insights about the classification of brain tumors by identifying cellular markers of phenotype and about tumor growth potential with nuclear markers of proliferation. In situ hybridization (ISH) research shows promise for diagnostic applications in tumor classification. The avidin-biotin conjugate IHC procedure is highlighted for diagnostic use on routinely processed clinical specimens. The immunophenotypes of brain tumors are tabulated in reference to their common IHC markers. Tumors that have been correctly classified by their IHC phenotypes include the giant-cell glioblastoma, primary brain lymphoma, and central neurocytoma. Phenotypes that may be more definitively detected by ISH, such as pituitary hormone, immunoglobulin light chain, and collagen messages are described. IHC of nuclear proliferation markers correlates with grade of malignancy, predicts tumor growth potential, and is prognostic for patient survival. The incorporation of bromodeoxyuridine, the expression of proliferating cell nuclear antigen, and the expression of Ki-67 antigen detected by MIB-1 antibody are compared in regard to their cell cycle activity and labeling index determinations. Fluorescence in situ hybridization (FISH) of brain tumor interphase nuclei and chromosomes is described. Abnormal FISH signals of specific chromosomes are associated with different types of brain tumors, with different grades of malignancy, and with mesenchymal drift of glioma cells in culture.

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“…Indeed, the presence of necrosis and vascular proliferation distinguishes glioblastoma multiforme from most other malignant brain tumours including astrocytomas (Germano et al, 1989). Previous investigators (Plate et al, 1992;Shweiki et al, 1992) noted marked up-regulation of VEGF expression in pallisading cells adjacent to necrosis and also in other small anaplastic cells at some distance from necrosis.…”

Section: mentioning

confidence: 99%

Vascular endothelial growth factor expression is independent of hypoxia in human malignant glioma spheroids and tumours

Parliament¹,

Allalunis-Turner²,

Franko³

et al. 2000

Br J Cancer

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Among the various adaptive responses to cell and tissue hypoxia is that of neoangiogenesis. This process occurs under physiological and pathophysiological conditions. It is becoming apparent that primary brain tumours of astrocytic lineage, especially glioblastoma multiforme, exhibit hypoxia-induced neoangiogenesis in vivo through induction of the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF) (Shweiki et al, 1992;Plate et al, 1992Plate et al, , 1994. A strong correlation was found between intense VEGF expression and severe hypoxia in situ in HT29 and EMT-6 spheroids (Waleh et al, 1995).Recently we have observed variable presence of hypoxia adjacent to necrosis in some xenografted glioma lines and spheroids (Parliament et al, 1997;Franko et al, 1998). The results were interpreted in terms of regional variations in oxygen consumption, based on the concept of modulation of oxygen consumption in regions of oxygen and nutrient deprivation in solid tumours (Hochachka et al, 1996). We were interested in determining the pattern of VEGF expression in situ, particularly in the nutrientdeprived regions of viable cells adjoining necrosis, which may or may not be severely hypoxic in human glioma spheroids and xenografts. We recently showed that the M006XLo line has elevated expression of VEGF under aerobic conditions, with modest hypoxic induction compared to the M006X line (AllalunisTurner et al, 1999). In this report we have examined the oxygen dependence of VEGF mRNA expression in the M006X line undergoing mild hypoxic stress (6% oxygen (O 2 )), and we have also examined VEGF expression in spheroids of both M006X and M006XLo lines and in xenograft tumours of the M059K, M006 and M010b lines. We also sought to independently validate the presence of radiobiologically hypoxic cells in situ in M006 tumours using the comet assay of in-situ DNA damage (Olive et al, 1997(Olive et al, , 1998.Finally, we have performed preliminary experiments to assess the presence of tumour-cell VEGF receptor (Vaisman et al, 1990) expression which has previously been seen in melanoma and ovarian carcinoma lines (Boocock et al, 1995;Liu et al, 1995), suggesting autocrine/paracrine growth stimulation.  Cell lines, spheroids and xenograftsDetails of the origin and characterization of the glioma cell lines used in this study have been previously published (Parliament et al, 1997;Allalunis-Turner et al, 1991 Summary We recently showed that severe hypoxia was not universally present adjacent to necrosis in human glioma xenografts and spheroids established from the M059K, M006, M006X, M006XLo and M010b cell lines. Using these glioma models, we wished to test whether oxygen serves as a regulator of cellular VEGF expression in situ. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect vascular endothelial growth factor (VEGF) mRNA and protein expression in sections of glioma xenografts and spheroids in which hypoxic regions and regions with well-oxygenated necrosis were identifie...

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Correlation of histopathological features and proliferative potential of gliomas

Cited by 54 publications

References 29 publications

Cell Kinetics Study of Upper Aerodigestive Tract Squamous Cell Carcinoma Using Bromodeoxyuridine

Cell Kinetics Study of Upper Aerodigestive Tract Squamous Cell Carcinoma Using Bromodeoxyuridine

Insights About Brain Tumors Gained Through Immunohistochemistry and in Situ Hybridization of Nuclear and Phenotypic Markers

Vascular endothelial growth factor expression is independent of hypoxia in human malignant glioma spheroids and tumours

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