Utility of Glucose Transporter 1 in the Distinction of Benign and Malignant Thoracic and Abdominal Mesothelial Lesions
ABSTRACT Malignant mesothelioma, of either peritoneum or pleura, is an uncommon cancer. The diagnosis is often difficult to make, in part because of the overlapping morphology of reactive and malignant mesothelial cells. Glucose transporter 1 (GLUT-1) is a glucose transporter typically found on erythrocytes, which is aberrantly expressed in various carcinomas. It has recently been reported as specific and sensitive in discriminating malignant pleural mesothelioma from reactive hyperplasia. The application of GLUT-1 staining in peritoneal mesothelioma has not been fully explored.
To determine if GLUT-1 staining is helpful in distinguishing abdominal mesotheliomas from benign, reactive mesothelial lesions and to further study its utility in the thorax.
Tissue microarrays containing 135 abdominal malignant mesotheliomas and 30 malignant pleural mesotheliomas were stained with an antibody to GLUT-1, as were 56 reactive mesothelial lesions.
The overall sensitivity and specificity for GLUT-1 in mesothelioma was 53% and 98%, respectively. The sensitivity in epithelioid malignant mesothelioma was 49% and in sarcomatoid/biphasic malignant mesothelioma, 66%. In the thorax, the sensitivity was 50% and in the abdomen it was 54%. The positive predictive value of GLUT-1 immunoreactivity was 98% and the negative predictive value was 40%.
Glucose transporter 1 staining of thoracic mesotheliomas showed high specificity but lower sensitivity than previously reported. Abdominal malignant mesotheliomas showed similar results. Because of low sensitivity, only positive staining is informative. In both sites, the utility of the stain was limited by nonspecific staining (eg, in necrotic areas) as well as bright labeling of erythrocytes and occasional lymphoid elements. Despite these limitations, GLUT-1 can help differentiate malignant mesothelioma from reactive benign mesothelium.
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ABSTRACT: Distinguishing malignant mesotheliomas from benign mesothelial proliferations on hematoxylin and eosin-stained sections can be extremely challenging. Various immunohistochemical stains have been suggested to help in making this distinction, but all are controversial. Recently, IMP3 (insulin-like growth factor II mRNA binding protein 3) and GLUT-1 (glucose transporter protein 1) have been proposed as immunohistochemical markers that are positive in mesotheliomas but not in benign proliferations. We evaluated the performance of these markers on a tissue microarray containing 30 malignant mesotheliomas and 48 benign thoracic or abdominal mesothelial proliferations. IMP3 was positive in 53% of malignant and 27% of benign cases (P=0.03), whereas GLUT-1 was positive in 60% of malignant and 13% of benign cases (P=0.0003). Forty-three percent of malignant cases, but only 4% of benign cases, were positive for both IMP3 and GLUT-1 (P=0.00003). We conclude that, statistically, both IMP3 and GLUT-1 are more frequently positive in malignant compared with benign mesothelial processes; however, the frequency of positive staining in benign cases is too high to allow their diagnostic use as single stains. The combination of both markers may be of greater diagnostic value, but this hypothesis should be confirmed in further studies.The American journal of surgical pathology 10/2012; 37(3). DOI:10.1097/PAS.0b013e31826ab1c0 · 4.59 Impact Factor
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ABSTRACT: Objective Mesothelial hyperplasia (MH) and fibrosing pleuritis (FP) can be difficult to distinguish from epithelioid (MM-E) and sarcomatoid (MM-S) malignant pleural mesotheliomas. GLUT-1 has shown variable results regarding its sensitivity and specificity when used to evaluate mesothelial proliferations. We evaluated the utility of GLUT-1 immunostaining in differentiating MH and FP from MM-E and MM-S. Materials and Methods In this retrospective study, diagnostically well-characterized cases (MH = 31, FP = 29, MM-E = 41, MM-S = 29) were collected and manually stained for GLUT-1. All slides were visually scored by 2 pathologists; using the following system: 0%, 1+ 1-25%, 2+ 26-50% and 3+ > 51% cells staining. Results All benign cases (n = 60) were negative for GLUT-1 while 45 of 78 (58%) MM [21 of 41 (50%) MM-E, 21 of 29 (72%) MM-S and 3 of 3 biphasic mesothelioma (100%)] had 1+ to 3+ staining. Of the MM-E, 10 had 1+, and 11 had 2+ staining; of the MM-S 3 had 1+, 15 had 2+ and 3 had 3+ staining. Both sarcomatoid and epithelioid components of the 3 biphasic mesotheliomas revealed 1+ staining. All 5 desmoplastic MM were negative. Conclusions Positive staining with GLUT-1 is helpful since it is present in half of MM-E and three-quarter of MM-S. Although all reactive mesothelial lesions were negative, the absence of immunoreactivity does not exclude the diagnosis of MM. As with all IHC stains used for diagnostic purposes, GLUT-1 has to be a part of a panel, and the results interpreted in the context of clinical, radiological and histological findings.Lung cancer (Amsterdam, Netherlands) 01/2013; DOI:10.1016/j.lungcan.2013.12.009 · 3.74 Impact Factor
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ABSTRACT: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare primary peritoneal malignancy. Its prognosis has been improved by an aggressive locoregional treatment combining extensive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic factors are currently poorly defined for this disease but are essential if treatment is to be standardized. Twenty-eight patients with DMPM, who were considered preoperatively to be candidates for CRS and HIPEC between June 1998 and August 2010 at our institution, were selected for this study. Medical records and histopathological features were retrospectively reviewed and 24 clinical, histological, and immunohistochemical parameters were assessed for their association with overall survival by univariate and multivariate analyses. The following factors were significantly associated with overall survival by univariate analysis: predominant histological growth pattern in the epithelioid areas, nuclear grooves in the epithelioid areas, atypical mitoses, and calretinin and GLUT1 expression by immunohistochemistry in the epithelioid areas. Expression of the facilitative glucose transporter protein GLUT1 in the epithelioid areas was the only factor independently associated with overall survival by multivariate analysis. GLUT1 expression appears to be an indicator of poor prognosis in DMPM. Standard histological classification of DMPM may not be adequate to select patients for aggressive locoregional treatments, such as CRS and HIPEC. Multicenter validation of the prognostic factors identified in this preliminary study is needed to refine patient selection for potential cure.Annals of Surgical Oncology 06/2013; 21(S4). DOI:10.1245/s10434-013-3077-4 · 3.94 Impact Factor