Glucose Transporter-1 Protein Expression in Thymic Epithelial Neoplasms: A Marker for Poor Prognosis
Sing Yun Chang, Sarah M Jenkins, Kelly K Edwards, Marie-Christine Aubry, Eunhee S Yi, Stephen D Cassivi, Yolanda I Garces, Anja C Roden. Mayo Clinic, Rochester, MN
Background: Glucose transporter-1 (GLUT-1) is involved in cellular glucose uptake and has been shown to be increased in malignant epithelial and mesothelial cells. In fact, we and others have demonstrated that GLUT-1 expression is higher in thymic carcinomas (TCa) than in thymomas. Evidence also suggests that GLUT-1 expression in carcinoma cells may be associated with resistance to radiation and chemotherapy and increased recurrence and metastasis. We studied the prognostic value of GLUT-1 expression in thymic epithelial neoplasms (TEN).
Design: Specimens from patients treated for TEN were included. Three pathologists independently classified all cases according to WHO. Type AB, B1 and B2 thymomas were excluded due to the high number of lymphocytes. Sections were stained for GLUT-1. The percentage of GLUT-1+ cells was expressed as 100*(number of + epithelial cells) / total number of epithelial cells (mean of 5 HPF counted). Cases with >5% GLUT-1+ cells were considered positive since most cases showed a few scattered GLUT-1+ epithelial cells. Logistic and Cox proportional hazards regression models were used for statistical analysis.
Results: 49 patients (20 women, 29 men; median age, 63 years, range, 18-85) were included. Pathologists agreed upon type A (n=16) and B3 (n=14) thymoma, or TCa (n=19). The median follow-up (n=44) time was 3.6 years (range, 12 days–20.5 years). GLUT-1 positivity was associated with modified Masaoka stage (p=0.01), increased risk of metastasis/recurrence (n=10, HR=8.72, p=0.01) and death (n=24, HR=2.72, p=0.03). GLUT-1 expression was also associated with WHO type (p=0.005) and was more commonly positive in TCa vs. type B3 and type A thymomas (% GLUT-1 positive cases, 78.9 vs 50.0 vs 18.7, respectively). In high-grade TCa GLUT-1 was expressed by a higher percentage of tumor cells (median, 80%) compared to low/intermediate grade TCa (median, 41%) (difference statistically not significant). When controlled for Masaoka stage and WHO, GLUT-1 expression was not an independent prognostic marker, however.
Conclusions: Our results show that increased GLUT-1 expression is associated with poorer prognosis, higher tumor stage and morphology when evaluated in type A and B3 thymoma and TCa. Although multivariate analysis does not show GLUT-1 as an independent prognostic marker in TEN, GLUT-1 expression may be useful in evaluating patient prognosis when combined with cell-kinetic parameters or other prognostic marker. Larger studies are necessary to evaluate GLUT-1 as prognostic factor in TCa.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 288, Wednesday Afternoon