Expression of phospho-p44/42MAPK in oral squamous cell carcinoma
Nur Mollaoglu(1,2)*, K. Andreas SCHLEGEL(1) , Takeshi TOYOSHIMA(4) , Emeka NKENKE(1) , Friedrich W. NEUKAM(1) , Yeliz KASKO(3) , Jutta RIES(1)
(1)Department of Oral and Maxillofacial Surgery, University of Erlangen, Germany (Head: Professor F. W. Neukam), (2) Gazi University, School of Dentistry, Department of Oral and Maxillofacial Surgery, Ankara-Turkey, (3) Ankara University, School of Agriculture, Department of Biometry and Genetics, Ankara, Turkey, (4) Department of Oral and Maxillofacial Surgery, Kyushu University, Fukuoka, Japan
Hellenic Archives of Oral & Maxillofacial Surgery (2010) 3, 121-128
SUMMARY: Oral squamous cell carcinoma (OSCC) has been one of the most common cancers world-wide. Activation of MAPK family, in particular extracellular-signal-regulated kinase ERK by phosphorylation has been reported to be the indicator for the malignant proliferation in various malignancies. The aim of the present study was to determine quantitatively the degree of ERK phosphorylation in OSCC. Patients and Methods: A total of 48 paraffin embedded OSCC samples was retrieved. Immunohistochemical staining was done using monoclonal antibody phosphop44/42MAPK. 10 samples taken from retromolar area of otherwise healthy patients who underwent to impacted third molar surgery were used as controls. Samples were taken during the surgery. The ERK phosphorylation was detected using labelling index (LI). Subsequent correlation of LI with clinico-pathological parameters was performed. Results: ERK was detectable in all the OSCC cases, not in negative controls. The mean LI was 35.17%. However, there was no statistically significant difference between ERK activation and clinico-pathological variables except gender (p<0.01). Conclusion: It was determined that pERK (phosphorylated ERK) is indicating clearly tumour differentiation. Nevertheless, there was no correlation between the ERK phosphorylation and clinico-pathological parameters of OSCC. Thus, results may suggest pERK has got a role in oral carcinogenesis but no role during the progression of malignant proliferation which increases the severity in OSCC.
KEY WORDS: Oral squamous cell carcinoma, MAPK, pERK, prognosis
REFERENCES
Albanell J, Codony-Servat J, Rojo F, Del Campo JM, Sauleda S, Anido J, Raspall G, Giralt J, Rosello J, Nicholson RI, Mendelsohn J, Baselga J: Activated extracellular signalregulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. Cancer Res 61: 6500-6510, 2001
Arends MJ, Wyllie AH: Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol 52: 223–54, 1991
Garavello W, Nicolini G, Aguzzi A, Aggioni D, Leone BE, Viganò P, Gaini RM, Tredici G: Selective reduction of extracellular signalregulated protein kinase (ERK) phosphorylation in squamous cell carcinoma of the larynx Oncology reports 16: 479-484, 2006
Gee J, Barroso A, Ellis I, Robertson J, Nicholson R: Biological and clinical associations of c-jun activation in human breast cancer. Int J Cancer 89: 177–186, 2000
Gioeli D, Mandell JW, Petroni GR, Frierson HFJ, Weber MJ: Activation of mitogen-activated protein kinase associated with prostate cancer progression. Cancer Res 59: 279–284, 1999
Ito Y, Sasaki Y, Horimoto M, Wada S, Tanaka Y, Kasahara A, Ueki T, Hirano T, Yamamoto H, Fujimoto J, Okamoto E, Hayashi N, Hori M: Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma. Hepatology 27: 951–958, 1998
Kademani D: Oral cancer. Mayo Clin Proc 82: 878-87, 2007
Orton RJ, Sturm OE, Vyshemirsky V, Calder M, Gilbert DR, Kolch W: Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem J 392: 249-261, 2005
Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH: Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22: 153-183, 2001
Rudolph P, Alm P, Heidebrecht HJ, Bolte H, Ratjen V, Baldetorp B, Fernö M, Olsson H, Parwaresch R: Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer. J Natl Cancer Inst 91: 271–8, 1999
Slaughter DP: Field cancerization” in oral stratified squamous epithelium: Clinical implications of multicentric origin. Cancer 6: 963- 968, 1953
Svensson S, Jirstrom K, Ryden L, Roos G, Emdin S, Ostrowski MC, Landberg G: ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis. Oncogene 23: 4370-9, 2005
Vairaktaris E, Spyridonidou S, Papakosta V, Vylliotis A, Lazaris A, Perrea D, Yapijakis C, Patsouris E: The hamster model of sequential oral oncogenesis. Oral Oncol 44: 315-24, 2008
Vicent S, Lopez-Picazo JM, Toledo G, Lozano MD, Torre W, GarciaCorchon C, Quero C, Soria JC, Martin-Algarra S, Manzano RG, Montuenga LM: ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours. Br J Cancer 8: 1047- 52, 2004
World Health Organization, “International histological classification of tumors. 2nd. ed. Berlin, Springer-Verlag 1988.
(1)Department of Oral and Maxillofacial Surgery, University of Erlangen, Germany (Head: Professor F. W. Neukam), (2) Gazi University, School of Dentistry, Department of Oral and Maxillofacial Surgery, Ankara-Turkey, (3) Ankara University, School of Agriculture, Department of Biometry and Genetics, Ankara, Turkey, (4) Department of Oral and Maxillofacial Surgery, Kyushu University, Fukuoka, Japan
Hellenic Archives of Oral & Maxillofacial Surgery (2010) 3, 121-128
SUMMARY: Oral squamous cell carcinoma (OSCC) has been one of the most common cancers world-wide. Activation of MAPK family, in particular extracellular-signal-regulated kinase ERK by phosphorylation has been reported to be the indicator for the malignant proliferation in various malignancies. The aim of the present study was to determine quantitatively the degree of ERK phosphorylation in OSCC. Patients and Methods: A total of 48 paraffin embedded OSCC samples was retrieved. Immunohistochemical staining was done using monoclonal antibody phosphop44/42MAPK. 10 samples taken from retromolar area of otherwise healthy patients who underwent to impacted third molar surgery were used as controls. Samples were taken during the surgery. The ERK phosphorylation was detected using labelling index (LI). Subsequent correlation of LI with clinico-pathological parameters was performed. Results: ERK was detectable in all the OSCC cases, not in negative controls. The mean LI was 35.17%. However, there was no statistically significant difference between ERK activation and clinico-pathological variables except gender (p<0.01). Conclusion: It was determined that pERK (phosphorylated ERK) is indicating clearly tumour differentiation. Nevertheless, there was no correlation between the ERK phosphorylation and clinico-pathological parameters of OSCC. Thus, results may suggest pERK has got a role in oral carcinogenesis but no role during the progression of malignant proliferation which increases the severity in OSCC.
KEY WORDS: Oral squamous cell carcinoma, MAPK, pERK, prognosis
REFERENCES
Albanell J, Codony-Servat J, Rojo F, Del Campo JM, Sauleda S, Anido J, Raspall G, Giralt J, Rosello J, Nicholson RI, Mendelsohn J, Baselga J: Activated extracellular signalregulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. Cancer Res 61: 6500-6510, 2001
Arends MJ, Wyllie AH: Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol 52: 223–54, 1991
Garavello W, Nicolini G, Aguzzi A, Aggioni D, Leone BE, Viganò P, Gaini RM, Tredici G: Selective reduction of extracellular signalregulated protein kinase (ERK) phosphorylation in squamous cell carcinoma of the larynx Oncology reports 16: 479-484, 2006
Gee J, Barroso A, Ellis I, Robertson J, Nicholson R: Biological and clinical associations of c-jun activation in human breast cancer. Int J Cancer 89: 177–186, 2000
Gioeli D, Mandell JW, Petroni GR, Frierson HFJ, Weber MJ: Activation of mitogen-activated protein kinase associated with prostate cancer progression. Cancer Res 59: 279–284, 1999
Ito Y, Sasaki Y, Horimoto M, Wada S, Tanaka Y, Kasahara A, Ueki T, Hirano T, Yamamoto H, Fujimoto J, Okamoto E, Hayashi N, Hori M: Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma. Hepatology 27: 951–958, 1998
Kademani D: Oral cancer. Mayo Clin Proc 82: 878-87, 2007
Orton RJ, Sturm OE, Vyshemirsky V, Calder M, Gilbert DR, Kolch W: Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem J 392: 249-261, 2005
Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH: Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22: 153-183, 2001
Rudolph P, Alm P, Heidebrecht HJ, Bolte H, Ratjen V, Baldetorp B, Fernö M, Olsson H, Parwaresch R: Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer. J Natl Cancer Inst 91: 271–8, 1999
Slaughter DP: Field cancerization” in oral stratified squamous epithelium: Clinical implications of multicentric origin. Cancer 6: 963- 968, 1953
Svensson S, Jirstrom K, Ryden L, Roos G, Emdin S, Ostrowski MC, Landberg G: ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis. Oncogene 23: 4370-9, 2005
Vairaktaris E, Spyridonidou S, Papakosta V, Vylliotis A, Lazaris A, Perrea D, Yapijakis C, Patsouris E: The hamster model of sequential oral oncogenesis. Oral Oncol 44: 315-24, 2008
Vicent S, Lopez-Picazo JM, Toledo G, Lozano MD, Torre W, GarciaCorchon C, Quero C, Soria JC, Martin-Algarra S, Manzano RG, Montuenga LM: ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours. Br J Cancer 8: 1047- 52, 2004
World Health Organization, “International histological classification of tumors. 2nd. ed. Berlin, Springer-Verlag 1988.
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