Technical Tips Useful in distinguishing benign reactive mesothelium (-) from malignant mesothelioma (+) Assists in distinguishing hemangioblastoma from renal cell carcinoma in children Useful along with Claudin 1 and EMA in the diagnosis of perineuriomas (vs. neurofibroma) Distinguishes benign endometrial hyperplasia from atypical endometrial hyperplasia and adenocarcinoma Expression has been associated with increased malignant potential, invasiveness, and a poor prognosis in general Expression of GLUT1 is a late event in colorectal cancer and expression in a high proportion of cancer cells is associated with a high incidence of lymph node metastases

Words From Our Pathologist:

Glucose transporters (Glut1-14) belong to a family of structurally-related proteins that mediate energy-independent glucose transport across the plasma membrane. These transporters differ in their tissue distribution and affinity for glucose. GLUT1 was the first member of the facilitated glucose transporter family identified. GLUT1, reacts with a 55 kD protein found in the erythrocyte membrane. It is a major glucose transporter in the mammalian blood-brain barrier, and also mediates glucose transport in endothelial cells, adipose tissue and cardiac muscle. GLUT1 is detectable in many human tissues including those of colon, lung, stomach, esophagus and breast. GLUT1 is overexpressed in malignant cells and in a variety of tumors of organs that include the breast, pancreas, cervix, endometrium, lung, mesothelium, colon, bladder, thyroid, bone, soft tissues, and oral cavity. As GLUT1 tends to be of higher staining intensity in the neoplastic cells farther from the local vascular supply, it has been suggested that once malignant cells have the ability to upregulate GLUT1 expression they do so in response to local environmental conditions such as hypoxia or low glucose levels.

GLUT1 and Mesothelioma
Morphologic differentiation between reactive mesothelium (RM) and malignant pleural mesothelioma (MPM) in small specimens can be a diagnostic challenge. The difficulty is compounded when neoplastic cells demonstrate only slight atypia. A study by Yasufumi Kato demonstrated that GLUT1 is a sensitive and specific immuohistochemical marker that can differentiate RM from MPM. In this study, GLUT1 was expressing in 100% (48 of 48) of MPMs and in none (0 of 40) of the cases of RM. This study included 30 cases of lung adenocarcinoma, of which 28 (96.5%) were positive for GLUT1. Other studies have reported the GLUT1 positivity rate in RM to be 0% (Afify et al.), 3% (Zimmerman et al.), and 20% (Burstein et al.). However, the staining characteristics in these studies indicated that the intensity to be equivocal-to-weak in the case of RM in contrast to the unequivocal positivity in the case of MPM.

GLUT1 and Liver Tumors
Diagnosing liver tumors can be difficult in the setting of a poorly differentiated tumor or tumors with no known prior malignancy. Frequently, alpha-fetoprotein, carcinoembryonic antigen, factor VIII, and mucicarmine have been employed to distinguish hepatocellular carcinoma (HCC) from adenocarcinoma. However, these stains have their limitations. CA 15-3 and GLUT1 are expressed in a variety of carcinomas. A study Zimmerman et al. showed that CA 15-3 stained 43 of 59 metastatic cancers to the liver and only 3 of 35 hepatocelluar carcinoma samples; GLUT1 stained 34 of 59 metastases and 2 of 35 HCCs. GLUT1, combined CA15-3 stained 52 of 59 metastases and 5 of 35 HCCs. Therefore, GLUT1 and CA15-3 are useful tools in discriminating HCC from other carcinomas.

GLUT1 and Endometrial Hyperplasia
Simple and complex endometrial hyperplasias without atypia, both of which have a low association with endometrial adenocarcinomas, tend to be GLUT1 negative (Ashton-Sager A et al.). In contrast, cases of complex atypical endometrial hyperplasia, which is associated with high risk for the development to endometrial carcinoma, tend to be positive for GLUT1. Thus, GLUT1 immunostaining could be helpful in distinguishing cases of hyperplasia with atypia from these without atypia.

GLUT1 and Prognosis
An association between GLUT1 expression and neoplastic progression has also been reported in colonic, ovarian, and esophageal neoplasia: benign tumors were negative for GLUT1; malignant tumors were positive. GLUT1 is strongly expressed in colorectal carcinomas, and the expression in a high proportion of colon cancer cells is associated with a high incidence of lymph node metastases, a late event in colorectal cancer. GLUT1 expression has been associated with increased malignant potential, invasiveness, and a poor prognosis. Thus the level of GLUT1 expression might be an independent prognostic factor in colon cancer

 

Mesothelial Cells: Malignant vs. Benign
	GLUT1	Mesothelin	Calretinin	p53
Malignant	+	+	+	+
Reactive Benign	-	+	+	-

Skin: Spindle Cell Tumors
	SM Actin	GLUT1	BG8	Factor VIII	Collagen IV	FLI-1	CD34	CD31	Factor XIIIa	CD99
Hemangiopericytoma	-	-	-	-	-	+	+	-	+/-	+/-
Hemangioma	+	+	+	+	+	+	+	+	-	-

Perineurioma vs. Neurofibroma
	Claudin 1	EMA	S-100	GLUT1
Perineurioma	+	+	-	+
Neurofibroma	+	+	-	-