- PROFESSOR Pathology
- PROFESSOR Oncological Sciences
MD, Harvard Medical School
Residency, Internal Medicine
Mount Auburn Hospital
NYU Medical Center
Children's Hospital Boston
Montefiore Medical Center
We are conducting both basic and applied research in the biology of cancer cells. We are investigating the clinical utility of three tumor marker: 1) phosphorylated histone H1 (collaboration with Dr. Kohtz, Pathology); 2) glucose transporter GLUT-1 (collaboration with Dr. Haber, Medicine); 3) a ras-oncogene-induced 31kd vesicle protein (collaboration with Dr.Hanson, Pathology). These markers appear to be of clinical value in the diagnosis and management of colon, ovarian, and breast cancer, and in body-cavity effusions. We are investigating applications in these and other malignancies such as bladder carcinoma. We are also investigating mechanisms of tumor growth suppression mediated by growth factors such as nerve growth factor, and by signal transduction-regulating proteins. The aim is to uncover new diagnostic, prognostic and therapeutic advances in cancer and other diseases which result from aberrant cell proliferation.
Weiser KR, Pritsker A, Reder I, Burstein D. GLUT1 glucose transporter expression in benign and malignant thyroid nodules. Thyroid 1997 Jun; 7(3): 363-7.Malignant cells exhibit increased rates of glycolysis and glucose uptake, the latter of which is mediated by glucose transport proteins. Because several types of cancer have been shown to express high levels of the GLUT1 glucose transporter isoform, we hypothesized that expression of GLUT1 might distinguish malignant from benign thyroid tissue. Archival thyroid tissue obtained at surgery was immunostained for GLUT1 protein. There were 38 benign cases (24 follicular adenoma, 1 Hurthle cell adenoma, 8 nodular goiter, 3 Hashimoto's thyroiditis, 2 Graves' disease) and 28 cases of thyroid cancer (17 papillary and its follicular variant, 6 follicular, 1 Hurthle cell, 2 anaplastic, 2 medullary). Normal thyroid tissue adjacent to nodules showed no thyrocyte staining in any case. No GLUT1 staining was seen in thyrocytes in benign nodular tissue, except for a single case of Hashimoto's thyroiditis in which a few Hurthle cells showed weak staining. Among the thyroid cancers, 13 of 28 (46%) showed tumor cell GLUT1 staining in at least some areas. This included 9 of 17 cases of papillary carcinoma and its follicular variant, 2 of 6 cases of follicular carcinoma and 2 of 2 cases of anaplastic carcinoma. Tumor cell GLUT1 staining was seen in two patterns: circumferential plasma membrane staining focally within the tumor, or asymmetric staining of the basilar aspect of tumor cells adjacent to stroma in some cases of papillary carcinoma. We conclude that GLUT1 expression is frequently detectable by immunostaining in thyroid cancer, but not in benign nodules or normal thyroid. GLUT1 expression may be a clinically useful molecular marker for thyroid cancer.
Burstein D, Reder I, Weiser K, Tong T, Pritsker A. GLUT1 glucose transporter: a highly sensitive marker of malignancy in body cavity effusions. Mod Pathol 1998 Apr; 11(4): 392-6.Malignant cells exhibit increased rates of glycolysis and glucose uptake, and several types of cancer have been reported to overexpress the GLUT1 glucose transporter. The diagnosis of malignancy in body cavity effusions remains a dilemma in certain cases, despite recent progress in diagnostic immunocytochemistry. We used immunostaining to detect the facilitative glucose transporter, GLUT1, in cytologic preparations of body cavity effusions and washes. With the use of standard avidin-biotin immunostaining for GLUT1, we examined cell blocks of body cavity effusions or washings from 31 carcinomas, 1 lymphoma, and 25 benign effusions or washes. GLUT1 staining occurred in the malignant cell population in 29 (93.5%) of 31 carcinomatous effusions or washes. The characteristic staining pattern consisted of dense, linear staining of the plasma membrane, with accentuation at cell-cell borders, with or without cytoplasmic staining. Erythrocytes showed positive GLUT1 membrane staining, consistent with previous reports. Of 25 benign effusions, 20 were nonstaining (excepting erythrocytes), and 5 contained rare single mesothelial cells, with equivocal to very weak membrane staining. Staining of these cells was readily distinguishable from the characteristic strong staining of malignant cells, and these cells were easily distinguished from tumor cells by their benign morphologic characteristics. At least three of these latter five specimens were from patients with cirrhosis. In all of the other cases, mesothelial cells, histiocytes, and other inflammatory cells did not stain. These findings suggest that GLUT1 immunostaining could be useful in diagnostic cytopathology. The findings also suggest that enhanced glycolysis, which requires increased glucose transport, might be a survival adaptation for tumor cells in effusions, a significant number of which are hypoxic.
Rathan A, Weiser KR, Pritsker A, Itzkowitz S, Bodian C, Slater G, Weiss A, Burstein D. GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis. Cancer 1998 Jul 1; 83(1): 34-40.BACKGROUND: Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. The authors hypothesized that GLUT1 glucose transporter expression is increased in colorectal carcinoma, and that the degree of expression might have prognostic significance. METHODS: GLUT1 glucose transporter immunostaining was studied in normal colon and benign colon adenomas and in 112 colorectal carcinomas from patients for whom long term clinical outcome was known. RESULTS: GLUT1 immunostaining was absent in normal colorectal epithelium and tubular adenomas, and absent or only weakly apparent in tubulovillous adenomas. The majority of carcinomas (101 of 112; 90%) had GLUT1 immunostaining. Tumors from 92 patients had low GLUT1 expression ( 50% of cells were GLUT1 positive) and 9 of these patients (45%) died of disease during follow-up. Disease specific mortality was greater in patients with high GLUT1 tumors (relative risk of 2.4; P=0.02). In a multivariate analysis to assess whether high GLUT1 staining correlated with increased mortality independently of Dukes stage, the risk of death from colon carcinoma in the group with high GLUT1 staining was 2.3 times that in the group with low GLUT1 staining, a difference that approached statistical significance (P=0.07). CONCLUSIONS: GLUT1 glucose transporter expression is associated strongly with neoplastic progression in the colon, and assessment of the extent of GLUT1 immunostaining in colorectal carcinoma identifies patients with a poorer prognosis.
Matsushima AY, Strauchen J, Lee G, Scigliano E, Hale EE, Weisse MT, Burstein D, Kamel O, Moore PS, Chang Y. Posttransplantation plasmacytic proliferations related to Kaposi's sarcoma-associated herpesvirus. Am J Surg Pathol 1999; 11: 1393-1400.
Weiser KR, Burstein D, Reder I, Pritsker A. GLUT1 glucose transporter expression in benign and malignant thyroid cells: An immunohistochemical study.;.
Kelman A, Rathan A, Leibowitz J, Burstein D. Thyroid cytology and the risk of malignancy in thyroid nodules: Importance of nuclear atypia in 'indeterminate' specimens.;.
Burstein D, Rathan A, Weiser K, Pritsker A, Itzkowitz S. GLUT-1 glucose transporter: A marker of neoplastic progression in colonic epithelial neoplasms.;.
Goldfischer M, Weiser K, Pritsker A, Burstein D. GLUT-1 glucose transporter expression in ovarian neoplasms: A marker of tumor progression.;.
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Dr. Burstein has not yet completed reporting of Industry relationships.
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