title: Ephrin receptor (Eph) -A1, -A2, -A4 and -A7 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival.
abstract: Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate the clinical significance of Eph-A1, -A2, -A4 and -A7 protein expression in mobile tongue squamous cell carcinoma (SCC). Eph-A1, -A2, -A4 and -A7 protein expression was assessed immunohistochemically on 37 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. All the examined mobile tongue SCC cases were found positive for Eph-A1, -A2, -A4 and -A7. Significant associations were noted between high Eph-A1, -A4 and -A7 expression and absence of lymph node metastases (p = 0.0263, p = 0.0461 and p = 0.0461, respectively). High Eph-A1, -A2 and -A7 expression was significantly more frequently observed in patients presenting absence of vascular invasion (p = 0.0444), dense stromal inflammatory reaction (p = 0.0063) and female gender (p = 0.0327), respectively. Mobile tongue SCC patients with high Eph-A7 expression presented longer overall and disease-free survival compared to those with low Eph-A7 expression (log-rank test, p = 0.0093 and p = 0.0164, respectively). In multivariate analysis, Eph-A7 expression was identified as independent prognostic factor of overall survival (Cox-regression analysis, p = 0.0426). The present study supported evidence that Ephs may participate in the malignant transformation of mobile tongue SCC, reinforcing their utility as clinical markers for patients' management and prognosis, as also as targets for potential therapeutic intervention in tongue chemoprevention.
authors.affiliation: Department of Pathology, Institut Curie, Paris, France, theocharis@ath.forthnet.gr.
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
authors.forename: Jerzy
authors.initials: J
authors.lastname: Klijanienko
authors.forename: Constantinos
authors.initials: C
authors.lastname: Giaginis
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Alexandrou
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D036081:Receptors, Eph Family / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D036081:Receptors, Eph Family
references.citation: Cancer. 2009 Jun 15;115(12):2684-92
references.pmid: 19396818
references.citation: Histopathology. 2011 Sep;59(3):514-25
references.pmid: 22034891
references.citation: Oral Oncol. 2002 Sep;38(6):610-7
references.pmid: 12167440
references.citation: Cancer. 1995 Apr 1;75(7):1649-56
references.pmid: 8826923
references.citation: World J Gastroenterol. 2008 Oct 7;14(37):5650-6
references.pmid: 18837080
references.citation: Br J Cancer. 2008 Oct 7;99(7):1121-8
references.pmid: 18766188
references.citation: Nat Rev Cancer. 2010 Mar;10(3):165-80
references.pmid: 20179713
references.citation: Angiogenesis. 2004;7(1):17-28
references.pmid: 15302992
references.citation: BMC Cancer. 2008 Mar 25;8:79
references.pmid: 18366728
references.citation: Mod Pathol. 2006 Oct;19(10):1369-77
references.pmid: 16862074
references.citation: Head Neck. 2002 Jun;24(6):513-20
references.pmid: 12112547
references.citation: Mod Pathol. 2009 Jan;22(1):151-60
references.pmid: 19011600
references.citation: Curr Cancer Drug Targets. 2005 May;5(3):149-57
references.pmid: 15892616
references.citation: Cytokine Growth Factor Rev. 2002 Feb;13(1):75-85
references.pmid: 11750881
references.citation: Int J Cancer. 2003 Feb 20;103(5):657-63
references.pmid: 12494475
references.citation: Clin Cancer Res. 2003 Feb;9(2):613-8
references.pmid: 12576426
references.citation: Oncol Rep. 2004 Mar;11(3):605-11
references.pmid: 14767510
references.citation: Cancer. 2005 May 1;103(9):1843-9
references.pmid: 15772957
references.citation: Oncology. 1997 Nov-Dec;54(6):463-7
references.pmid: 9394842
references.citation: Exp Cell Res. 2006 Mar 10;312(5):642-50
references.pmid: 16330025
references.citation: Cytokine Growth Factor Rev. 2004 Dec;15(6):419-33
references.pmid: 15561600
references.citation: Br J Cancer. 2000 Sep;83(5):614-9
references.pmid: 10944601
references.citation: Cancer Biol Ther. 2009 Jun;8(11):1027-34
references.pmid: 19395869
references.citation: Cancer Metastasis Rev. 2007 Dec;26(3-4):645-62
references.pmid: 17768600
references.citation: Clin Cancer Res. 2006 Jan 15;12(2):353-60
references.pmid: 16428472
references.citation: Microsc Res Tech. 2002 Oct 1;59(1):58-67
references.pmid: 12242697
references.citation: Histol Histopathol. 2008 Aug;23(8):1011-23
references.pmid: 18498077
references.citation: J Clin Pathol. 2007 Oct;60(10):1086-91
references.pmid: 17158642
references.citation: J Pathol. 2006 Mar;208(4):453-61
references.pmid: 16470907
references.citation: Oral Oncol. 2008 Dec;44(12):1110-7
references.pmid: 18485799
references.citation: Lancet. 2002 Oct 12;360(9340):1131-5
references.pmid: 12387961
references.citation: Cancer Res. 2010 Jan 1;70(1):299-308
references.pmid: 20028874
references.citation: Oncol Rep. 2008 Jan;19(1):151-6
references.pmid: 18097589
references.citation: Curr Pharm Des. 2004;10(27):3431-42
references.pmid: 15544526
references.citation: Cancer Res. 2005 Aug 1;65(15):6910-8
references.pmid: 16061675
references.citation: Expert Opin Ther Targets. 2011 Jan;15(1):31-51
references.pmid: 21142802
references.citation: Cancer. 2007 Jan 15;109(2):332-40
references.pmid: 17154180
references.citation: Pathol Oncol Res. 2009 Sep;15(3):473-8
references.pmid: 19048396
references.citation: Am J Surg Pathol. 2005 Feb;29(2):167-78
references.pmid: 15644773
references.citation: Clin Cancer Res. 2005 Jan 1;11(1):226-31
references.pmid: 15671550
references.citation: Cell. 2008 Apr 4;133(1):38-52
references.pmid: 18394988
references.citation: Am J Pathol. 2003 Dec;163(6):2271-6
references.pmid: 14633601
references.citation: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references.pmid: 17237035
references.citation: Med Sci Monit. 2011 Sep;17(9):BR257-65
references.pmid: 21873938
references.citation: Pathol Oncol Res. 2010 Jun;16(2):267-76
references.pmid: 19949912
references.citation: J Oral Pathol Med. 2011 Oct;40(9):706-14
references.pmid: 21457345