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Erschienen in: Clinical Oral Investigations 5/2017

08.09.2016 | Original Article

The prognostic value of GLUT-1 staining in the detection of malignant transformation in oral mucosa

verfasst von: Roman C. Brands, Olga Köhler, Stephan Rauthe, Stefan Hartmann, Harald Ebhardt, Axel Seher, Christian Linz, Alexander C. Kübler, Urs D.A. Müller-Richter

Erschienen in: Clinical Oral Investigations | Ausgabe 5/2017

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Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most common tumor entity worldwide. Unfortunately, the multimodal treatment consisting of surgery, radiation, and chemotherapy does not show the desired efficacy. The intent of this study was to evaluate the sensitivity and specificity of an oral brush biopsy in combination with glucose transporter (GLUT)-1 staining in identifying premalignant and malignant lesions.

Methods

A total of 72 patients were included in the study, divided into four diagnostic subgroups (24 healthy, 15 carcinoma, 18 leukoplakia, 15 oral lichen planus). Oral brush biopsies were taken and analyzed for GLUT-1 expression by immunocytologic staining. Incisional biopsy served as the gold standard.

Results

Twelve (80 %) of the 15 carcinomas, nine (50 %) of the 18 leukoplakia, nine (60 %) of the 15 oral lichen planus, and none of the healthy specimens stained positive for GLUT-1. This resulted in a sensitivity rate of 80 % and a specificity rate of 68.42 %. Diagnostic accuracy was 70.83 % based on the correct diagnoses in 51 of 72 patients.

Conclusion

An oral brush biopsy can easily be performed throughout the entire oral cavity, is noninvasive, and shows high sensitivity and specificity rates with conventional cytology or computer-assisted analysis.

Clinical relevance

The significance of GLUT-1-specific staining with an oral brush biopsy is more limited than expected but could be used as an additional tool in detecting malignant transformation in the oral cavity.
Literatur
1.
Zurück zum Zitat Gupta S, Shah JS, Parikh S, Limbdiwala P, Goel S (2014) Clinical correlative study on early detection of oral cancer and precancerous lesions by modified oral brush biopsy and cytology followed by histopathology. J Cancer Res Ther 10:232–238CrossRefPubMed Gupta S, Shah JS, Parikh S, Limbdiwala P, Goel S (2014) Clinical correlative study on early detection of oral cancer and precancerous lesions by modified oral brush biopsy and cytology followed by histopathology. J Cancer Res Ther 10:232–238CrossRefPubMed
3.
Zurück zum Zitat Boyle P (2008) World cancer report 2008. Int Agency Res Cancer Boyle P (2008) World cancer report 2008. Int Agency Res Cancer
4.
Zurück zum Zitat Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium-clinical implications of multicentric origin. Cancer 6:963–968CrossRefPubMed Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium-clinical implications of multicentric origin. Cancer 6:963–968CrossRefPubMed
5.
Zurück zum Zitat Simple M, Suresh A, Das D, Kuriakose MA (2015) Cancer stem cells and field cancerization of oral squamous cell carcinoma. Oral Oncol 51:643–651CrossRefPubMed Simple M, Suresh A, Das D, Kuriakose MA (2015) Cancer stem cells and field cancerization of oral squamous cell carcinoma. Oral Oncol 51:643–651CrossRefPubMed
6.
Zurück zum Zitat Richards D (2015) Adjunctive tests cannot replace scalpel biopsy for oral cancer diagnosis. Evid Based Dent 16:46–47CrossRefPubMed Richards D (2015) Adjunctive tests cannot replace scalpel biopsy for oral cancer diagnosis. Evid Based Dent 16:46–47CrossRefPubMed
7.
Zurück zum Zitat Driemel O, Kunkel M, Hullmann M, von Eggeling F, Muller-Richter U, Kosmehl H, et al. (2007) Diagnosis of oral squamous cell carcinoma and its precursor lesions. J Dtsch Dermatol Ges 5:1095–1100CrossRefPubMed Driemel O, Kunkel M, Hullmann M, von Eggeling F, Muller-Richter U, Kosmehl H, et al. (2007) Diagnosis of oral squamous cell carcinoma and its precursor lesions. J Dtsch Dermatol Ges 5:1095–1100CrossRefPubMed
8.
Zurück zum Zitat Shrikhande SV, Büchler MW (2008) Surgery of pancreatic tumors Shrikhande SV, Büchler MW (2008) Surgery of pancreatic tumors
10.
Zurück zum Zitat Balkwill FR, Capasso M, Hagemann T (2012) The tumor microenvironment at a glance. J Cell Sci 125:5591–5596CrossRefPubMed Balkwill FR, Capasso M, Hagemann T (2012) The tumor microenvironment at a glance. J Cell Sci 125:5591–5596CrossRefPubMed
11.
Zurück zum Zitat Foster JG, Wong SCK, Sharp TV (2014) The hypoxic tumor microenvironment: driving the tumorigenesis of non-small-cell lung cancer. Future Oncol 10:2659–2674CrossRefPubMed Foster JG, Wong SCK, Sharp TV (2014) The hypoxic tumor microenvironment: driving the tumorigenesis of non-small-cell lung cancer. Future Oncol 10:2659–2674CrossRefPubMed
12.
Zurück zum Zitat Eckert AW, Lautner MHW, Schutze A, Taubert H, Schubert J, Bilkenroth U (2011) Coexpression of hypoxia-inducible factor-1 alpha and glucose transporter-1 is associated with poor prognosis in oral squamous cell carcinoma patients. Histopathology 58:1136–1147CrossRefPubMed Eckert AW, Lautner MHW, Schutze A, Taubert H, Schubert J, Bilkenroth U (2011) Coexpression of hypoxia-inducible factor-1 alpha and glucose transporter-1 is associated with poor prognosis in oral squamous cell carcinoma patients. Histopathology 58:1136–1147CrossRefPubMed
13.
Zurück zum Zitat Ganapathy V, Thangaraju M, Prasad PD (2009) Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 121:29–40CrossRefPubMed Ganapathy V, Thangaraju M, Prasad PD (2009) Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 121:29–40CrossRefPubMed
14.
Zurück zum Zitat Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033CrossRefPubMedPubMedCentral Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Oliveira LR, Ribeiro-Silva A (2011) Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 40:298–307CrossRefPubMed Oliveira LR, Ribeiro-Silva A (2011) Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 40:298–307CrossRefPubMed
16.
Zurück zum Zitat Oliver RJ, Woodwards RT, Sloan P, Thakker NS, Stratford IJ, Airley RE (2004) Prognostic value of facilitative glucose transporter Glut-1 in oral squamous cell carcinomas treated by surgical resection; results of EORTC Translational Research Fund studies. Eur J Cancer 40:503–507CrossRefPubMed Oliver RJ, Woodwards RT, Sloan P, Thakker NS, Stratford IJ, Airley RE (2004) Prognostic value of facilitative glucose transporter Glut-1 in oral squamous cell carcinomas treated by surgical resection; results of EORTC Translational Research Fund studies. Eur J Cancer 40:503–507CrossRefPubMed
17.
Zurück zum Zitat Kunkel M, Moergel M, Stockinger M, Jeong JH, Fritz G, Lehr HA, et al. (2007) Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity. Oral Oncol 43:796–803CrossRefPubMed Kunkel M, Moergel M, Stockinger M, Jeong JH, Fritz G, Lehr HA, et al. (2007) Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity. Oral Oncol 43:796–803CrossRefPubMed
18.
Zurück zum Zitat Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, et al. (2003) Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 97:1015–1024CrossRefPubMed Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, et al. (2003) Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 97:1015–1024CrossRefPubMed
19.
Zurück zum Zitat Fukuzumi M, Hamakawa H, Onishi A, Sumida T, Tanioka H (2000) Gene expression of GLUT isoforms and VHL in oral squamous cell carcinoma. Cancer Lett 161:133–140CrossRefPubMed Fukuzumi M, Hamakawa H, Onishi A, Sumida T, Tanioka H (2000) Gene expression of GLUT isoforms and VHL in oral squamous cell carcinoma. Cancer Lett 161:133–140CrossRefPubMed
20.
Zurück zum Zitat Ayala FR, Rocha RM, Carvalho KC, Carvalho AL, da Cunha IW, Lourenco SV, et al. (2010) GLUT1 and GLUT3 as potential prognostic markers for oral squamous cell carcinoma. Molecules 15:2374–2387CrossRefPubMed Ayala FR, Rocha RM, Carvalho KC, Carvalho AL, da Cunha IW, Lourenco SV, et al. (2010) GLUT1 and GLUT3 as potential prognostic markers for oral squamous cell carcinoma. Molecules 15:2374–2387CrossRefPubMed
21.
Zurück zum Zitat Li S, Yang X, Wang P, Ran X (2013) The effects of GLUT1 on the survival of head and neck squamous cell carcinoma. Cell Physiol Biochem 32:624–634CrossRefPubMed Li S, Yang X, Wang P, Ran X (2013) The effects of GLUT1 on the survival of head and neck squamous cell carcinoma. Cell Physiol Biochem 32:624–634CrossRefPubMed
22.
Zurück zum Zitat Reisser C, Eichhorn K, Herold-Mende C, Born AI, Bannasch P (1999) Expression of facilitative glucose transport proteins during development of squamous cell carcinomas of the head and neck. Int J Cancer 80:194–198CrossRefPubMed Reisser C, Eichhorn K, Herold-Mende C, Born AI, Bannasch P (1999) Expression of facilitative glucose transport proteins during development of squamous cell carcinomas of the head and neck. Int J Cancer 80:194–198CrossRefPubMed
23.
Zurück zum Zitat Rhodus NL (2009) Oral cancer and precancer: improving outcomes. Compend Contin Educ Dent 30:486–488 490-484, 496-488 passim; quiz 504, 520PubMed Rhodus NL (2009) Oral cancer and precancer: improving outcomes. Compend Contin Educ Dent 30:486–488 490-484, 496-488 passim; quiz 504, 520PubMed
24.
Zurück zum Zitat Lingen MW, Kalmar JR, Karrison T, Speight PM (2008) Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol 44:10–22CrossRefPubMed Lingen MW, Kalmar JR, Karrison T, Speight PM (2008) Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol 44:10–22CrossRefPubMed
25.
26.
Zurück zum Zitat Belcher R, Hayes K, Fedewa S, Chen AY (2014) Current treatment of head and neck squamous cell cancer. J Surg Oncol 110:551–574CrossRefPubMed Belcher R, Hayes K, Fedewa S, Chen AY (2014) Current treatment of head and neck squamous cell cancer. J Surg Oncol 110:551–574CrossRefPubMed
27.
Zurück zum Zitat Vermorken JB, Specenier P (2010) Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol 21(Suppl 7):vii252–vii261PubMed Vermorken JB, Specenier P (2010) Optimal treatment for recurrent/metastatic head and neck cancer. Ann Oncol 21(Suppl 7):vii252–vii261PubMed
28.
Zurück zum Zitat Murphy CT, Galloway TJ, Handorf EA, Egleston BL, Wang LS, Mehra R, et al. (2016) Survival impact of increasing time to treatment initiation for patients with head and neck cancer in the United States. J Clin Oncol 34:169–178CrossRefPubMed Murphy CT, Galloway TJ, Handorf EA, Egleston BL, Wang LS, Mehra R, et al. (2016) Survival impact of increasing time to treatment initiation for patients with head and neck cancer in the United States. J Clin Oncol 34:169–178CrossRefPubMed
30.
Zurück zum Zitat Pizzi S, Porzionato A, Pasquali C, Guidolin D, Sperti C, Fogar P, et al. (2009) Glucose transporter-1 expression and prognostic significance in pancreatic carcinogenesis. Histol Histopathol 24:175–185PubMed Pizzi S, Porzionato A, Pasquali C, Guidolin D, Sperti C, Fogar P, et al. (2009) Glucose transporter-1 expression and prognostic significance in pancreatic carcinogenesis. Histol Histopathol 24:175–185PubMed
31.
Zurück zum Zitat Cho H, Lee YS, Kim J, Chung JY, Kim JH (2013) Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer. Cancer Investig 31:607–615CrossRef Cho H, Lee YS, Kim J, Chung JY, Kim JH (2013) Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer. Cancer Investig 31:607–615CrossRef
32.
Zurück zum Zitat Jozwiak P, Krzeslak A, Brys M, Lipinska A (2015) Glucose-dependent glucose transporter 1 expression and its impact on viability of thyroid cancer cells. Oncol Rep 33:913–920PubMed Jozwiak P, Krzeslak A, Brys M, Lipinska A (2015) Glucose-dependent glucose transporter 1 expression and its impact on viability of thyroid cancer cells. Oncol Rep 33:913–920PubMed
33.
Zurück zum Zitat Eckert AW, Kappler M, Schubert J, Taubert H (2012) Correlation of expression of hypoxia-related proteins with prognosis in oral squamous cell carcinoma patients. Oral Maxillofac Surg 16:189–196CrossRefPubMed Eckert AW, Kappler M, Schubert J, Taubert H (2012) Correlation of expression of hypoxia-related proteins with prognosis in oral squamous cell carcinoma patients. Oral Maxillofac Surg 16:189–196CrossRefPubMed
34.
Zurück zum Zitat Ohba S, Fujii H, Ito S, Fujimaki M, Matsumoto F, Furukawa M, et al. (2010) Overexpression of GLUT-1 in the invasion front is associated with depth of oral squamous cell carcinoma and prognosis. J Oral Pathol Med 39:74–78CrossRefPubMed Ohba S, Fujii H, Ito S, Fujimaki M, Matsumoto F, Furukawa M, et al. (2010) Overexpression of GLUT-1 in the invasion front is associated with depth of oral squamous cell carcinoma and prognosis. J Oral Pathol Med 39:74–78CrossRefPubMed
35.
Zurück zum Zitat Babshet M, Nandimath K, Pervatikar S, Naikmasur V (2011) Efficacy of oral brush cytology in the evaluation of the oral premalignant and malignant lesions. J Cytol 28:165–172CrossRefPubMedPubMedCentral Babshet M, Nandimath K, Pervatikar S, Naikmasur V (2011) Efficacy of oral brush cytology in the evaluation of the oral premalignant and malignant lesions. J Cytol 28:165–172CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Hohlweg-Majert B, Deppe H, Metzger MC, Schumm S, Hoefler H, Kesting MR, et al. (2009) Sensitivity and specificity of oral brush biopsy. Cancer Investig 27:293–297CrossRef Hohlweg-Majert B, Deppe H, Metzger MC, Schumm S, Hoefler H, Kesting MR, et al. (2009) Sensitivity and specificity of oral brush biopsy. Cancer Investig 27:293–297CrossRef
37.
Zurück zum Zitat Poate TW, Buchanan JA, Hodgson TA, Speight PM, Barrett AW, Moles DR, et al. (2004) An audit of the efficacy of the oral brush biopsy technique in a specialist oral medicine unit. Oral Oncol 40:829–834CrossRefPubMed Poate TW, Buchanan JA, Hodgson TA, Speight PM, Barrett AW, Moles DR, et al. (2004) An audit of the efficacy of the oral brush biopsy technique in a specialist oral medicine unit. Oral Oncol 40:829–834CrossRefPubMed
38.
Zurück zum Zitat Bhoopathi V, Kabani S, Mascarenhas AK (2009) Low positive predictive value of the oral brush biopsy in detecting dysplastic oral lesions. Cancer 115:1036–1040CrossRefPubMed Bhoopathi V, Kabani S, Mascarenhas AK (2009) Low positive predictive value of the oral brush biopsy in detecting dysplastic oral lesions. Cancer 115:1036–1040CrossRefPubMed
39.
Zurück zum Zitat Sousa FA, Paradella TC, Brandao AA, Rosa LE (2009) Oral lichen planus versus epithelial dysplasia: difficulties in diagnosis. Braz J Otorhinolaryngol 75:716–720PubMed Sousa FA, Paradella TC, Brandao AA, Rosa LE (2009) Oral lichen planus versus epithelial dysplasia: difficulties in diagnosis. Braz J Otorhinolaryngol 75:716–720PubMed
40.
Zurück zum Zitat Lundstrom IM (1983) Incidence of diabetes mellitus in patients with oral lichen planus. Int J Oral Surg 12:147–152CrossRefPubMed Lundstrom IM (1983) Incidence of diabetes mellitus in patients with oral lichen planus. Int J Oral Surg 12:147–152CrossRefPubMed
41.
Zurück zum Zitat Seyhan M, Ozcan H, Sahin I, Bayram N, Karincaoglu Y (2007) High prevalence of glucose metabolism disturbance in patients with lichen planus. Diabetes Res Clin Pract 77:198–202CrossRefPubMed Seyhan M, Ozcan H, Sahin I, Bayram N, Karincaoglu Y (2007) High prevalence of glucose metabolism disturbance in patients with lichen planus. Diabetes Res Clin Pract 77:198–202CrossRefPubMed
42.
Zurück zum Zitat Krauss E, Rauthe S, Gattenlohner S, Reuther T, Kochel M, Kriegebaum U, et al. (2011) MAGE-A antigens in lesions of the oral mucosa. Clin Oral Investig 15:315–320CrossRefPubMed Krauss E, Rauthe S, Gattenlohner S, Reuther T, Kochel M, Kriegebaum U, et al. (2011) MAGE-A antigens in lesions of the oral mucosa. Clin Oral Investig 15:315–320CrossRefPubMed
43.
Zurück zum Zitat Hartmann S, Kipke RU, Rauthe S, Mutzbauer G, Brands RC, Ebhardt H, et al. (2015) Oral brush biopsy and melanoma-associated antigens A (MAGE-A) staining in clinically suspicious lesions. J Craniomaxillofac Surg 43:2214–2218CrossRefPubMed Hartmann S, Kipke RU, Rauthe S, Mutzbauer G, Brands RC, Ebhardt H, et al. (2015) Oral brush biopsy and melanoma-associated antigens A (MAGE-A) staining in clinically suspicious lesions. J Craniomaxillofac Surg 43:2214–2218CrossRefPubMed
44.
Zurück zum Zitat Proia NK, Paszkiewicz GM, Nasca MA, Franke GE, Pauly JL (2006) Smoking and smokeless tobacco-associated human buccal cell mutations and their association with oral cancer—a review. Cancer Epidemiol Biomark Prev 15:1061–1077CrossRef Proia NK, Paszkiewicz GM, Nasca MA, Franke GE, Pauly JL (2006) Smoking and smokeless tobacco-associated human buccal cell mutations and their association with oral cancer—a review. Cancer Epidemiol Biomark Prev 15:1061–1077CrossRef
Metadaten
Titel
The prognostic value of GLUT-1 staining in the detection of malignant transformation in oral mucosa
verfasst von
Roman C. Brands
Olga Köhler
Stephan Rauthe
Stefan Hartmann
Harald Ebhardt
Axel Seher
Christian Linz
Alexander C. Kübler
Urs D.A. Müller-Richter
Publikationsdatum
08.09.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Oral Investigations / Ausgabe 5/2017
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-016-1954-5

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