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"Pinther, Berit"
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Both GLUT-1 and GLUT-14 are Independent Prognostic Factors in Gastric Adenocarcinoma
Background
The role of glucose transporter 14 (GLUT-14/SLC2A14) in tumor biology is entirely unknown, and the significance of hypoxia inducible factor 1-alpha (HIF1-α) for gastric adenocarcinoma is controversial. The impact of GLUT-1/SLC2A1 has never been confirmed in a Caucasian cohort.
Methods
Between 1996 and 2007, 124 patients underwent gastrectomy for gastric adenocarcinoma. Tumor sections were incubated with GLUT-1, GLUT-14, and HIF1-α antibodies. Expression was analyzed for correlations with histopathology, marker coexpression, and patient survival by uni- and multivariate analyses.
Results
Expressions of GLUT-1, GLUT-14, and HIF1-α were detectable in 50, 77.4, and 27.1 %, respectively. Expression of GLUT-1 was associated with pT-category (
p
= 0.019), pN-category (
p
= 0.019), tubular (WHO,
p
= 0.008), and intestinal (Lauren classification;
p
= 0.002) histologic subtypes. Expression of GLUT-14 was correlated with pT category (
p
= 0.043), whereas HIF1-α did not show any correlation with histopathology or survival. The median survival period was 14 months (95 % confidence interval [CI] 9.2–18.8 months) for GLUT-1-positive patients and 55 months (95 % CI 25.8–84.2;
p
= 0.01) for GLUT-1-negative patients. An inferior prognosis also was seen for GLUT-14-positive cases compared with GLUT-14-negative cases (
p
= 0.004). Thus, worst survival was seen with both GLUT-1- and GLUT-14-positive expression followed by single-positive and then double-negative cases (
p
= 0.004). In multivariate analysis including International Union Against Cancer (UICC) stages, R category, Lauren classification, surgery alone versus neoadjuvant/perioperative chemotherapy, and marker expression as covariates, GLUT-1 (
p
= 0.011) and GLUT-14 (
p
= 0.025) kept their prognostic independence.
Conclusions
The study findings suggest that detection of GLUT-1 and GLUT-14 is of high prognostic value. It gives additional information to UICC stages and identifies patients with inferior prognosis. If confirmed in prospective studies, these markers need to be considered for future classification systems.
Journal Article
Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids
Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (
n
=54), genome/exome (
n
=44) and transcriptome (
n
=69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the cases, respectively, with
MEN1
,
PSIP1
and
ARID1A
being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine lung tumours,
TP53
and
RB1
mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumours but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin-remodelling genes is sufficient to drive transformation in pulmonary carcinoids.
Pulmonary carcinoids account for about 2% of pulmonary neoplasms. Here, the authors carry out gene copy number analysis, genome/exome, and transcriptome sequencing of pulmonary carcinoids and identify frequent mutations in chromatin-remodelling genes that can drive tumorigenesis in these tumours.
Journal Article