Human erythrocyte glucose transporter (Glut1) is immunohistochemically detected as a late event during malignant progression in Barrett\u27s metaplasia

We have previously demonstrated that the human erythrocyte glucose transporter (Glut1) is expressed in adenocarcinoma arising in Barrett\u27s metaplasia (BM). We have also shown that Glut1 is expressed as a late event during colorectal carcinogenesis. The aim of this work was to determine the chronology of Glut1 expression during the neoplastic progression in Barrett\u27s metaplasia. Formalin-fixed, paraffin-embedded tissue sections of 251 biopsies from 97 patients with BM were immunostained with the anti-Glut1 antibody MYM, after microwave-aided antigen retrieval, using the standard avidin-biotin complex immunoperoxidase technique. Dysplasia was graded as negative (ND), low grade (LGD)/indefinite or high grade (HGD). None of the 181 biopsies with ND (0%) or 51 biopsies with LGD (0%) showed Glut1 immunoreactivity. More importantly, although 0 of 6 biopsies with HGD (0%) expressed Glut1, 9 of 13 biopsies with adenocarcinoma (69%) were Glut1 positive (P = 0.0108, Fisher\u27s exact test). Our results indicate that Glut1 is expressed as a late event during the neoplastic progression in BM. Prospective studies are needed to determine the clinical utility of Glut1 immunoreactivity as a marker of carcinoma in patients with BM

Immunohistochemical detection of glut 3 in human tumors and normal tissues

Malignant cells have been shown to utilize more glucose than normal cells in vitro and in vivo. Glut3 is a member of the facilitative glucose transporters family of transmembrane proteins, and its mRNA levels has been found to be elevated in human cancers, indicating that it may play a role in glucose uptake by cancer cells. Localization and extent of expression of Glut3 protein in normal and malignant human tissues is still largely unknown. We studied Glut3 expression in a series of 325 benign and malignant human tissues using standard immunoperoxidase technique. Of the normal tissues tested, Glut3 immunoreactivity was detected only in normal testis and placenta. Twelve of 14 (86%) testicular, 3 of 22 (16%) ovarian, 2 of 8 (25%) gastric, and 11 of 41 (27%) non-small cell lung carcinomas were positive for Glut3. Other carcinomas, including those of the breast and colon, were negative. Only in Glut3-positive testicular carcinomas were most tumor cells Glut3-positive. We conclude that a) Glut3 has a limited expression in normal and malignant human tissues, as determined by immunohistochemical staining, b) Glut3 may play a role in glucose uptake in a subset of carcinomas of the lung, stomach and ovary, and, therefore, these tumors may have a distinct clinical behavior, and c) Glut3 may be an attractive target for monoclonal therapy or imaging of testicular germ cell tumors

p53 protein accumulation is a specific marker of malignant potential in Barrett\u27s metaplasia

Our aim was to determine the sensitivity and specificity of p53 accumulation as a marker of malignant potential in Barrett\u27s metaplasia (BM). One hundred eighty biopsies from 61 patients with BM were evaluated for p53 accumulation by immunohistochemistry. Of 25 patients with LGD, 9 had p53-positive biopsies, and of these 5 (56%) developed HGD/CA, whereas 16 had p53-negative biopsies and none (0%) developed HGD/CA after similar follow-up times (P = 0.0108). As a marker of malignant potential in BM, p53 accumulation has a sensitivity of 100%, specificity of 93%, and a predictive value of a positive test of 0.56, compared to sensitivity of 100%, specificity of 64%, and predictive value of a positive test of 0.2 for a histologic diagnosis of LGD. We conclude that: (1) p53 accumulation is more specific and has better predictive value for subsequent development of HGD/CA than histologic diagnosis of LGD. (2) Patients with LGD and p53-positive biopsies are more likely to develop HGD/CA; therefore, they should be followed up more closely than those with LGD and p53-negative biopsies

Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers

Glucose uptake has been found to be increased in cancer cells. Previous work has shown increased expression of the human erythrocyte glucose transporter (Glut1) mRNA in some human cancers, indicating that Glut1 may play a significant role in glucose uptake by these tumors. The distribution of Glut1 protein in normal and malignant human tissues is still largely unknown. Using immunohistochemistry, we found that Glut1 is largely undetectable in normal epithelial tissues and benign epithelial tumors but is expressed in a significant proportion of a variety of human carcinomas. We hypothesize that Glut1 expression by human carcinomas indicates an increased glucose uptake, and probably increased utilization of energy, which may correlate with an aggressive behavior. The biological significance of Glut1 expression needs to be determined