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. 2010 Apr 1;15(4):2374-87.
doi: 10.3390/molecules15042374.

GLUT1 and GLUT3 as potential prognostic markers for Oral Squamous Cell Carcinoma

Fernanda Rocha Rojas Ayala  1 , Rafael Malagoli Rocha, Kátia Cândido Carvalho, André Lopes Carvalho, Isabela Werneck da Cunha, Silvia Vanessa Lourenço, Fernando Augusto Soares
Affiliations

GLUT1 and GLUT3 as potential prognostic markers for Oral Squamous Cell Carcinoma

Fernanda Rocha Rojas Ayala et al. Molecules. .

Abstract

We associated clinical-pathological features of 142 OSCC with the expression pattern of GLUT1 and GLUT3 in order to estimate their prognostic value.

Methods: Clinical-pathological features and overall survival data of 142 patients with Oral Squamous Cell Carcinoma (OSCC) were retrospectively reviewed from A.C.Camargo hospital records. A tissue microarray (TMA) was built for the immunohistochemical (IHC) analysis of GLUT 1 and GLUT 3. IHC results were evaluated according to the staining pattern and number of positive cells.

Results: GLUT 1 was over expressed in 50.3% of OSSC cases showing membrane staining pattern. However, nuclear expression was observed in 49.7% of the analyzed cases. GLUT 3 over expression was detected in 21.1% of OSCC cases. The pattern of GLUT 1 expression showed significant association with alcohol consumption (p = 0.004). Positive cell membrane GLUT 3 protein expression was associated with advanced clinic-staging of tumours (p = 0.005) as well as with vascular embolization (p = 0.005). Positive expression of GLUT 3 was associated with unfavorable free-disease survival (p = 0.021).

Conclusion: GLUT1 and GLUT3 protein expression evaluated by immunohistochemistry are, significantly, indicators of poor prognosis outcome in oral squamous cell carcinoma, probably due to the enhanced glycolytic metabolism of more aggressive neoplastic cells.

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Figures

Figure 1
Figure 1
A) GLUT1 membrane immunostaining in oral squamous cell carcinoma, 400×; B) GLUT1 expression in oral squamous cell carcinoma. Note both GLUT1 expression: membrane and nucleus (arrows), 200×; C) GLUT3 membrane immunostaining in oral squamous cell carcinoma; D) No GLUT3 immunostaining. Note also GLUT3 expression in the inflammatory cells, 200×.
Figure 2
Figure 2
A) Keratinizing squamous carcinoma. GLUT1, prostromal staining pattern. Note positivity at periphery of tumour nest, in non-keratinizing basaloid cells, and loss of GLUT1 expression accompanying keratinization at the centre of tumour nest, 200×; B) 400×; C) Non - keratinizing poorly differentiated carcinoma, 100×. In the absence of squamous differentiation/keratinization: GLUT1 displays an antistromal pattern, suggestive of hipoxia-driven GLUT1 induction. D) and E) Basal staning pattern with the superficial layers showing little or no GLUT1 staining in the normal epithelium; F) GLUT1 immunostain (arrow). Squamous intraepithelial neoplasia, non- staining of basal layer.
Figure 3
Figure 3
a) Kaplan –Meier curve of overall survival at five years in patients with OSCC (52.1%); b) Overall survival as a function of GLUT1 staining pattern (p = 0.015); c) Overall survival as a function of GLUT1 frequency, according to stratified cells (p = 0.041); d) Overall survival as a function of GLUT3 staining pattern (negative or positive) (p = 0.002).
Figure 3
Figure 3
a) Kaplan –Meier curve of overall survival at five years in patients with OSCC (52.1%); b) Overall survival as a function of GLUT1 staining pattern (p = 0.015); c) Overall survival as a function of GLUT1 frequency, according to stratified cells (p = 0.041); d) Overall survival as a function of GLUT3 staining pattern (negative or positive) (p = 0.002).
Figure 4
Figure 4
Kaplan–Meier curve of recurrence-free survival in 5 year in OSCC (64.8%).
Figure 5
Figure 5
Kaplan – Meier curve of disease - free survival as a function of GLUT3 staining pattern (p = 0.021).
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