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Erschienen in: Head and Neck Pathology 4/2021

11.04.2021 | Original Paper

Differential Expression of Potential Biomarkers of Oral Squamous Cell Carcinoma Development

verfasst von: Paola Fernandes Pansini, Isabella Bittencourt do Valle, Thabata Coeli Dias Damasceno, Priscila Marinho de Abreu, Anna Clara Gregório Có, Rossana Verónica Mendoza López, Jeferson Lenzi, Ricardo Mai Rocha, Evandro Duccini Souza, Maria Paula Curado, Hisham Mehanna, Paul Nankivell, José Roberto Vasconcelos de Podestá, Sandra Ventorin von Zeidler

Erschienen in: Head and Neck Pathology | Ausgabe 4/2021

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Abstract

To evaluate molecular epithelial changes, we investigated whether a profile of survivin, cyclin dependent kinase inhibitor 2A (CDKN2A), epidermal growth factor receptor (EGFR), polo like kinase 1 (PLK1), p63, p40 (Δnp63 isoform), cyclin D1 (CCND1) and BCL2 apoptosis regulator (BCL2) proteins could predict malignant transformation. Different tissue segments (tumor adjacent epithelium; dysplasia and tumor) from a total of 109 patients were analyzed by immunohistochemistry. An increased expression of survivin (p < 0.001), PLK1 (p = 0.001), and p63 (p < 0.001) in parallel to reduced immunostaining of p40 (p < 0.001) and BCL2 (p = 0.029) was observed among the tissue segments analyzed. Our study revealed that survivin, PLK1, p63, p40 and BCL2 play a role in oral tumorigenesis and represent promising biomarkers able to recognize mesenchymal phenotype induction in the transition from nonmalignant cells to tumor cells. These results reveals critical interaction between survivin, PLK1, p63, p40 promising proteins during invasive carcinoma development.
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Literatur
1.
Zurück zum Zitat Cao M, Jiang Y, Tang Y, Liang X. The crosstalk between lncRNA and microRNA in cancer metastasis: orchestrating the epithelial-mesenchymal plasticity. Oncotarget. 2015;8:12472–83.CrossRef Cao M, Jiang Y, Tang Y, Liang X. The crosstalk between lncRNA and microRNA in cancer metastasis: orchestrating the epithelial-mesenchymal plasticity. Oncotarget. 2015;8:12472–83.CrossRef
2.
Zurück zum Zitat Chaw SY, Abdul Majeed A, Dalley AJ, Chan A, Stein S, Farah CS. Epithelial to mesenchymal transition (EMT) biomarkers—E-cadherin, beta-catenin, APC and Vimentin - In oral squamous cell carcinogenesis and transformation. Oral Oncol. 2012;48:997–1006.CrossRef Chaw SY, Abdul Majeed A, Dalley AJ, Chan A, Stein S, Farah CS. Epithelial to mesenchymal transition (EMT) biomarkers—E-cadherin, beta-catenin, APC and Vimentin - In oral squamous cell carcinogenesis and transformation. Oral Oncol. 2012;48:997–1006.CrossRef
3.
Zurück zum Zitat Meka NJ, Ugrappa S, Velpula N, Kumar S, Maloth KN, Kodangal S. Quantitative immunoexpression of EGFR in oral potentially malignant disorders: oral leukoplakia and oral submucous fibrosis. J Dental Res Dental Clin Dental Prosp. 2015;9(3):166.CrossRef Meka NJ, Ugrappa S, Velpula N, Kumar S, Maloth KN, Kodangal S. Quantitative immunoexpression of EGFR in oral potentially malignant disorders: oral leukoplakia and oral submucous fibrosis. J Dental Res Dental Clin Dental Prosp. 2015;9(3):166.CrossRef
4.
Zurück zum Zitat El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. WHO classification of head and neck tumours. Int Agency Res Cancer; 2017. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. WHO classification of head and neck tumours. Int Agency Res Cancer; 2017.
5.
Zurück zum Zitat Rakesh N, Iyengar A, Majumdar K, Vidya GS, Shantha Kumar SS. Quantitative evaluation of tumour - associated tissue eosinophilia and cyclo-oxegenase-2 gene in oral cancer patients with assessment of long term outcomes. Pathol Oncol Res. 2016;22:385–92.CrossRef Rakesh N, Iyengar A, Majumdar K, Vidya GS, Shantha Kumar SS. Quantitative evaluation of tumour - associated tissue eosinophilia and cyclo-oxegenase-2 gene in oral cancer patients with assessment of long term outcomes. Pathol Oncol Res. 2016;22:385–92.CrossRef
6.
Zurück zum Zitat Awadallah M, Idle M, Patel K, Kademani D. Management update of potentially premalignant oral epithelial lesions. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125:628–36.CrossRef Awadallah M, Idle M, Patel K, Kademani D. Management update of potentially premalignant oral epithelial lesions. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018;125:628–36.CrossRef
7.
Zurück zum Zitat Hwang JTK, Gu YR, Shen M, Ralhan R, Walfis PG, Pritzker KPH, et al. Individualized five year risk assessment for oral premalignant lesion progression to cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123:374–81.CrossRef Hwang JTK, Gu YR, Shen M, Ralhan R, Walfis PG, Pritzker KPH, et al. Individualized five year risk assessment for oral premalignant lesion progression to cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123:374–81.CrossRef
8.
Zurück zum Zitat Pang S, Yee M, Saba Y, Chino T. Artepillin C as a targeting survivin molecule in oral squamous cell carcinoma cells in vitro: a preliminary study. J Oral Pathol Med. 2018;47:48–52.CrossRef Pang S, Yee M, Saba Y, Chino T. Artepillin C as a targeting survivin molecule in oral squamous cell carcinoma cells in vitro: a preliminary study. J Oral Pathol Med. 2018;47:48–52.CrossRef
9.
Zurück zum Zitat Liu S, Shi L, Yang X, Ye D, Wang T, Dong C, et al. Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma. Cell Cycle. 2017;16:894–902.CrossRef Liu S, Shi L, Yang X, Ye D, Wang T, Dong C, et al. Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma. Cell Cycle. 2017;16:894–902.CrossRef
10.
Zurück zum Zitat Joseph JP, Harishankar MK, Pillai AA, Devi A. Hypoxia induced EMT: a review on the mechanism of tumor progression and metastasis in OSCC. Oral Oncol. 2018;80:23–32.CrossRef Joseph JP, Harishankar MK, Pillai AA, Devi A. Hypoxia induced EMT: a review on the mechanism of tumor progression and metastasis in OSCC. Oral Oncol. 2018;80:23–32.CrossRef
11.
Zurück zum Zitat Sah NK, Seniya C. Survivin splice variants and their diagnostic significance. Tumor Biol. 2015;36:6623–31.CrossRef Sah NK, Seniya C. Survivin splice variants and their diagnostic significance. Tumor Biol. 2015;36:6623–31.CrossRef
12.
Zurück zum Zitat Radha G, Raghavan SC. BBA - reviews on Cancer BCL2: a promising cancer therapeutic target. BBA Rev Cancer. 2017;1868:309–14. Radha G, Raghavan SC. BBA - reviews on Cancer BCL2: a promising cancer therapeutic target. BBA Rev Cancer. 2017;1868:309–14.
13.
Zurück zum Zitat Ruan J, Xu P, Fan W, Deng QYM. Quantitative assessment of aberrant P16INK4a methylation in ovarian cancer: a meta-analysis based on literature and TCGA datasets. Cancer Manag Res. 2018;10:3033–46.CrossRef Ruan J, Xu P, Fan W, Deng QYM. Quantitative assessment of aberrant P16INK4a methylation in ovarian cancer: a meta-analysis based on literature and TCGA datasets. Cancer Manag Res. 2018;10:3033–46.CrossRef
14.
Zurück zum Zitat Kumar S, Kim J. PLK-1 targeted inhibitors and their potential against tumorigenesis. London: Hindawi Publishing Corporation; 2015.CrossRef Kumar S, Kim J. PLK-1 targeted inhibitors and their potential against tumorigenesis. London: Hindawi Publishing Corporation; 2015.CrossRef
15.
Zurück zum Zitat Mazorra Z, Chao L, Lavastida A, Sanchez B, Ramos M, Iznaga N, et al. Seminars in oncology nimotuzumab: beyond the EGFR signaling cascade inhibition. Semin Oncol. 2018;45:18–26.CrossRef Mazorra Z, Chao L, Lavastida A, Sanchez B, Ramos M, Iznaga N, et al. Seminars in oncology nimotuzumab: beyond the EGFR signaling cascade inhibition. Semin Oncol. 2018;45:18–26.CrossRef
16.
Zurück zum Zitat Qie S, Diehl JA. Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med. 2017;94:1313–26.CrossRef Qie S, Diehl JA. Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med. 2017;94:1313–26.CrossRef
17.
Zurück zum Zitat Gonfloni S, Caputo V, Iannizzotto V. P63 in health and cancer. Int J Dev Biol. 2015;93:87–93.CrossRef Gonfloni S, Caputo V, Iannizzotto V. P63 in health and cancer. Int J Dev Biol. 2015;93:87–93.CrossRef
18.
Zurück zum Zitat Candi E, Smirnov A, Panatta E, Maria A, Cristina M, Novelli F, et al. Metabolic pathways regulated by p63. Biochem Biophys Res Commun. 2017;482:440–4.CrossRef Candi E, Smirnov A, Panatta E, Maria A, Cristina M, Novelli F, et al. Metabolic pathways regulated by p63. Biochem Biophys Res Commun. 2017;482:440–4.CrossRef
19.
Zurück zum Zitat Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition AJCC Cancer Staging Manual and the Future of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRef Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition AJCC Cancer Staging Manual and the Future of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRef
20.
Zurück zum Zitat Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, Sloan P. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42:987–93.CrossRef Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, Sloan P. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42:987–93.CrossRef
21.
Zurück zum Zitat Pickhard A, Gröber S, Haug AK, Piontek G, Wirth M, Straben U, et al. Survivin and pAkt as potential prognostic markers in squamous cell carcinoma of the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:733–42.CrossRef Pickhard A, Gröber S, Haug AK, Piontek G, Wirth M, Straben U, et al. Survivin and pAkt as potential prognostic markers in squamous cell carcinoma of the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:733–42.CrossRef
22.
Zurück zum Zitat Villa A, Sonis S. Oral leukoplakia remains a challenging condition. Oral Dis. 2018;24:179–83.CrossRef Villa A, Sonis S. Oral leukoplakia remains a challenging condition. Oral Dis. 2018;24:179–83.CrossRef
23.
Zurück zum Zitat Bienk K, Anacl D, Flores C. Predictive value of p63, ki-67, and survivin expression in oral leukoplakia: a tissue microarray study. Microsc Res Tech. 2017;80:845–50.CrossRef Bienk K, Anacl D, Flores C. Predictive value of p63, ki-67, and survivin expression in oral leukoplakia: a tissue microarray study. Microsc Res Tech. 2017;80:845–50.CrossRef
24.
Zurück zum Zitat Graziano V, De Laurenzi V. Role of p63 in cancer development. BBA Rev Cancer. 2011;1816:57–66. Graziano V, De Laurenzi V. Role of p63 in cancer development. BBA Rev Cancer. 2011;1816:57–66.
25.
Zurück zum Zitat Saintigny P, El-naggar AK, Papadimitrakopoulou V, Ren H, Fan Y, Feng L, et al. DeltaNp63 overexpression, alone and in combination with other biomarkers, predicts the development of oral cancer in patients with leukoplakia. NIH Public Access. 2010;15:6284–91. Saintigny P, El-naggar AK, Papadimitrakopoulou V, Ren H, Fan Y, Feng L, et al. DeltaNp63 overexpression, alone and in combination with other biomarkers, predicts the development of oral cancer in patients with leukoplakia. NIH Public Access. 2010;15:6284–91.
26.
Zurück zum Zitat Patel SB, Manjunatha BS, Shah V, Soni N, Sutariya R. Immunohistochemical evaluation of p63 and cyclin D1 in oral squamous cell carcinoma and leukoplakia. J Korean Assoc Oral Maxillofac Surg. 2017;43:324–30.CrossRef Patel SB, Manjunatha BS, Shah V, Soni N, Sutariya R. Immunohistochemical evaluation of p63 and cyclin D1 in oral squamous cell carcinoma and leukoplakia. J Korean Assoc Oral Maxillofac Surg. 2017;43:324–30.CrossRef
27.
Zurück zum Zitat Yao J, Chen J. Roles of p63 in epidermal development and tumorigenesis. Biomedicine. 2012;35:457–63. Yao J, Chen J. Roles of p63 in epidermal development and tumorigenesis. Biomedicine. 2012;35:457–63.
28.
Zurück zum Zitat Goto Y, Kawano S, Matsubara R, Kiyosue T. Possible involvement of D Np63 downregulation in the invasion and metastasis of oral squamous cell carcinoma via induction of a mesenchymal phenotype. Clin Exp Metast. 2014;31:293–306.CrossRef Goto Y, Kawano S, Matsubara R, Kiyosue T. Possible involvement of D Np63 downregulation in the invasion and metastasis of oral squamous cell carcinoma via induction of a mesenchymal phenotype. Clin Exp Metast. 2014;31:293–306.CrossRef
29.
Zurück zum Zitat Matsubara R, Kawano S, Kiyosue T, Goto Y, Hirano M, Jinno T, et al. Increased Δ Np63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma. Int J Oncol. 2011;39:1391–9.PubMed Matsubara R, Kawano S, Kiyosue T, Goto Y, Hirano M, Jinno T, et al. Increased Δ Np63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma. Int J Oncol. 2011;39:1391–9.PubMed
30.
Zurück zum Zitat Garewal J, Garewal R, Sircar K. Expession of Bcl-2 and MIB-1 markers in oral squamous cell carcinoma- a comparative study. J Clin Diagn Res. 2014;8:2–5. Garewal J, Garewal R, Sircar K. Expession of Bcl-2 and MIB-1 markers in oral squamous cell carcinoma- a comparative study. J Clin Diagn Res. 2014;8:2–5.
31.
Zurück zum Zitat Loro LL, Johannessen AC, Vintermyr OK. Decreased expression of bcl-2 in moderate and severe oral epithelia dysplasias. Oral Oncol. 2002;38:691–8.CrossRef Loro LL, Johannessen AC, Vintermyr OK. Decreased expression of bcl-2 in moderate and severe oral epithelia dysplasias. Oral Oncol. 2002;38:691–8.CrossRef
32.
Zurück zum Zitat Juneja S, Chaitanya N, Agarwal M. Immunohistochemical expression of Bcl-2 in oral epithelial dysplasia and oral squamous cell carcinoma. Indian J Cancer. 2016;52:505.CrossRef Juneja S, Chaitanya N, Agarwal M. Immunohistochemical expression of Bcl-2 in oral epithelial dysplasia and oral squamous cell carcinoma. Indian J Cancer. 2016;52:505.CrossRef
33.
Zurück zum Zitat Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 2003;3:46–54.CrossRef Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 2003;3:46–54.CrossRef
34.
Zurück zum Zitat Poomsawat S, Punyasingh J, Vejchapipat P. Overexpression of survivin and caspase 3 in oral carcinogenesis. Appl Immunohistochem Mol Morphol. 2014;22:65–71.CrossRef Poomsawat S, Punyasingh J, Vejchapipat P. Overexpression of survivin and caspase 3 in oral carcinogenesis. Appl Immunohistochem Mol Morphol. 2014;22:65–71.CrossRef
35.
Zurück zum Zitat Kanter M, Turan G, Usta C, Usta A, Esen HH, Tavlı L, et al. Survivin and cycline D1 expressions are associated with malignant potential in mucinous ovarian neoplasms. J Mol Histol. 2016;47:145–52.CrossRef Kanter M, Turan G, Usta C, Usta A, Esen HH, Tavlı L, et al. Survivin and cycline D1 expressions are associated with malignant potential in mucinous ovarian neoplasms. J Mol Histol. 2016;47:145–52.CrossRef
36.
Zurück zum Zitat Li C, Yan Y, Ji W, Bao L, Qian H, Chen L, et al. OCT4 positively regulates survivin expression to promote cancer cell proliferation and leads to poor prognosis in esophageal squamous cell carcinoma. PLoS ONE. 2012;7:1–10. Li C, Yan Y, Ji W, Bao L, Qian H, Chen L, et al. OCT4 positively regulates survivin expression to promote cancer cell proliferation and leads to poor prognosis in esophageal squamous cell carcinoma. PLoS ONE. 2012;7:1–10.
37.
Zurück zum Zitat Knecht R, Oberhauser C, Strebhardt K. PLK (polo-like kinase), a new prognostic marker for oropharyngeal carcinomas. Int J Cancer. 2000;89:535–6.CrossRef Knecht R, Oberhauser C, Strebhardt K. PLK (polo-like kinase), a new prognostic marker for oropharyngeal carcinomas. Int J Cancer. 2000;89:535–6.CrossRef
38.
Zurück zum Zitat Khan Z, Khan AA, Yadav H, Prasad GBKS, Bisen PS. Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma. Cell Mol Biol Lett. 2017;22:1–32.CrossRef Khan Z, Khan AA, Yadav H, Prasad GBKS, Bisen PS. Survivin, a molecular target for therapeutic interventions in squamous cell carcinoma. Cell Mol Biol Lett. 2017;22:1–32.CrossRef
39.
Zurück zum Zitat Lo Muzio L, Pannone G, Staibano S, Mignogna MD, Rubini C, Mariggiò MA, et al. Survivin expression in oral squamous cell carcinoma. Br J Cancer. 2003;89:2244–8.CrossRef Lo Muzio L, Pannone G, Staibano S, Mignogna MD, Rubini C, Mariggiò MA, et al. Survivin expression in oral squamous cell carcinoma. Br J Cancer. 2003;89:2244–8.CrossRef
40.
Zurück zum Zitat Rivera C, Gallegos R, Figueroa C. Biomarkers of progression to oral cancer in patients with dysplasia: a systematic review. Mol Clin Oncol. 2020;13:1–7.CrossRef Rivera C, Gallegos R, Figueroa C. Biomarkers of progression to oral cancer in patients with dysplasia: a systematic review. Mol Clin Oncol. 2020;13:1–7.CrossRef
Metadaten
Titel
Differential Expression of Potential Biomarkers of Oral Squamous Cell Carcinoma Development
verfasst von
Paola Fernandes Pansini
Isabella Bittencourt do Valle
Thabata Coeli Dias Damasceno
Priscila Marinho de Abreu
Anna Clara Gregório Có
Rossana Verónica Mendoza López
Jeferson Lenzi
Ricardo Mai Rocha
Evandro Duccini Souza
Maria Paula Curado
Hisham Mehanna
Paul Nankivell
José Roberto Vasconcelos de Podestá
Sandra Ventorin von Zeidler
Publikationsdatum
11.04.2021
Verlag
Springer US
Erschienen in
Head and Neck Pathology / Ausgabe 4/2021
Elektronische ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-021-01322-8

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