trisialoganglioside-gt1 and Brain-Neoplasms

We studied ganglioside expression in 12 human metastatic brain tumors metastasized from colon (4), renal (3), lung (2), esophagus (1), pancreas (1), and mammary (1) carcinomas. GM3 was the major common ganglioside expressed in brain metastatic tumor tissues, and GT1b was also present in all the metastatic brain tumor tissues. The latter was identified by TLC-immunostaining and characterized structurally by secondary ion mass spectrometry combined with 'Far-Eastern blot'. The immunohistochemical analysis of frozen tissue sections confirmed localization of GT1b in the tumor cell membrane or cytosol. GT1b was shown to be expressed both in the primary colon carcinoma and the metastasis of a single patient by immunohistochemical procedure. In systemic carcinomas without brain metastasis, GM3 was a common major component, but no GT1b was detected. These findings indicate that GT1b is a brain metastasis-associated ganglioside. We speculate that the presence of GT1b would be a useful marker for estimating metastatic potentials to the brain.

Topics: Adenocarcinoma; Biomarkers, Tumor; Brain Neoplasms; Chromatography, Thin Layer; Colonic Neoplasms; Frozen Sections; G(M3) Ganglioside; Gangliosides; Humans; Immunohistochemistry; Kidney Neoplasms; Mass Spectrometry; Neoplasm Metastasis

Classification/grading schemes for brain tumors are based mainly on histologic examinations, but these have major limitations, which has led to a search for more objective prognostic markers. Gangliosides have several biologic effects relevant to tumors, and ganglioside compositions of primary brain tumors correlate with diagnosis. This led to the authors' hypothesis that ganglioside patterns of brain tumors might be useful as prognostic indicators.. Gangliosides in primary brain tumors of different histologic types from 84 patients were analyzed. Specific ganglioside patterns and several other relevant variables were examined for associations with survival using a Cox proportional hazards model. Kaplan-Meier survival curves were analyzed using the log-rank test.. Patients in whom less than 30% of total tumor gangliosides consisted of 1b pathway gangliosides (GD1b, GT1b, and GQ1b) had significantly higher risk ratios than those with more than 30% 1b gangliosides (P approximately 0.03). The presence of 6'-LM1 (NeuAc alpha 2-->6Gal beta 1-->4Glc-NAc beta 1-->3Gal beta 1-->4Glc beta 1-->1Cer was also associated with a higher risk ratio (P approximately 0.007). Combinations of 1b gangliosides and 6'-LM1 identified three groups of patients regardless of histologic diagnosis. Group A, with less than 30% 1b and the presence of 6'-LM1, had a median survival time of 331 days. Group B, with less than 30% 1b but no 6'-LM1, had a median survival time of more than 698 days. Group C, with more than 30% 1b had a median survival time of more than 776 days.. The correlation of ganglioside patterns with survival in this initial investigation suggests the potential of 1b gangliosides and 6'-LM1 to be used as prognostic indicators. Continuing research is being conducted to assess this possibility prospectively.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Brain Neoplasms; Carbohydrate Sequence; Child; Child, Preschool; Female; Gangliosides; Humans; Infant; Male; Middle Aged; Molecular Sequence Data; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Survival Rate

Limitations of classification schemes for brain tumors based solely on morphology have stimulated searches for molecular markers of nosologic and prognostic value. Gangliosides are logical candidates because there are high concentrations of them in the nervous system, there is evidence of their roles in regulation of growth and differentiation, and data from small series suggest correlations between ganglioside composition and glioma type.. Ganglioside compositions were determined for 70 primary human brain tumors: 16 low grade astrocytomas (LG), 12 anaplastic astrocytomas (AA), 34 glioblastoma multiformes (GBM), and 8 primitive neuroectodermal tumors (PNET). This method involved identification and quantitation of specific gangliosides using chemical analysis and immunoanalysis.. Among all tumor types, histologic grade correlated with a progressive loss of 1b gangliosides (P < 0.0001). GQ1b was higher in LGs than in AAs (P < 0.001). Both GT1b and GD1b were higher in AAs than GBMs (P < 0.01 and 0.05, respectively) and lower in PNETs than in GBMs (P < 0.05). GM3 was higher in PNETs than in any astrocytoma group and higher in GBMs than in either AAs or LGs. There was a significant difference in the content of 3'-LM1 among all groups (P < 0.005), between AAs and GBMs (P < 0.05), and between low grade ordinary and juvenile pilocytic astrocyomas (P < 0.01). The lacto-series ganglioside 3'-isoLM1 was present in all groups except PNET.. These results indicate that patterns of gangliosides could be of considerable value in refining the classification and diagnosis of primary human brain tumors.

Topics: Adult; Aged; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Female; G(M1) Ganglioside; G(M3) Ganglioside; Gangliosides; Glioblastoma; Humans; Male; Middle Aged; Nerve Growth Factors; Neuroectodermal Tumors, Primitive, Peripheral