J Breast Cancer.  2012 Jun;15(2):172-180. 10.4048/jbc.2012.15.2.172.

The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas

• Jang SM
• Han H
• Jang KS
• Jun YJ
• Jang SH
• Min KW
• Chung MS
• Paik SS

• KMID: 2242187
• DOI: http://doi.org/10.4048/jbc.2012.15.2.172

Abstract

PURPOSE
Glucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas.
METHODS
We used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis.
RESULTS
Membranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively).
CONCLUSION
GLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.

Keyword

Breast; Glucose transporter 1; Invasive ductal carcinoma; Prognosis

MeSH Terms

Breast
Carcinoma, Ductal
Carcinoma, Intraductal, Noninfiltrating
Disease-Free Survival
Estrogens
Glucose
Glucose Transport Proteins, Facilitative
Humans
Hyperplasia
Immunohistochemistry
Lymph Nodes
Medical Records
Neoplasm Metastasis
Phenotype
Prognosis
Proportional Hazards Models
Receptors, Progesterone
Estrogens
Glucose
Glucose Transport Proteins, Facilitative
Receptors, Progesterone

Figure

• 

  Figure 1 Glucose transporter 1 (GLUT1) expression in normal breast (NL), ductal hyperplasia (DH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and lymph node metastasis (LNM).

• 

  Figure 2 Representative photomicrographs of glucose transporter 1 (GLUT1) immunostaining in invasive ductal carcinomas (×200). (A) Negative (arrows: RBCs as internal control), (B) low expression (<10%), (C) moderate expression (10-50%), and (D) high expression (>50%).

• 

  Figure 3 Cumulative overall survival curves according to glucose transporter 1 (GLUT1) expression (A), American Joint Committee on Cancer (AJCC) stage (B), lymphatic invasion (C), and perinodal tumor extension (D) (Kaplan-Meier method with log-rank test).

• 

  Figure 4 Cumulative disease-free survival curves according to glucose transporter 1 (GLUT1) expression (A), American Joint Committee on Cancer (AJCC) stage (B), lymphatic invasion (C), and perinodal tumor extension (D) (Kaplan-Meier method with log-rank test).

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