Skip to main content
Erschienen in: Indian Journal of Surgical Oncology 1/2021

19.02.2020 | Original Article

TRF2 Overexpression at the Surgical Resection Margin: A Potential Predictive Biomarker in Oral Squamous Cell Carcinoma for Recurrence

verfasst von: Madhabananda Kar, Mahesh Sultania, Souvick Roy, Swatishree Padhi, Birendranath Banerjee

Erschienen in: Indian Journal of Surgical Oncology | Sonderheft 1/2021

Einloggen, um Zugang zu erhalten

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers in India with high incidence rate in eastern region due to habits of tobacco, pan and gutkha chewing habits. In majority of OSCC, the cases were presented to clinicians at later stages of the disease which leads to increased mortality. In addition presence of minimal residual disease also significantly contributed towards disease progression. Therefore, identification of potential biomarker for prognostic stratification of patients with high risk of disease recurrence and appropriate management is utmost necessary. In this study, 80 OSCC patients were included and their tumour specimen along with cut margin (CM) was collected after surgical excision. Immunohistochemistry (IHC) was performed to check expression of TRF2 in tumour and CM of OSCC patients. Statistical analysis was carried out using SPSS based on clinical and pathological records. It was observed that 27 OSCC patients developed recurrence during the period of the study (2012–2016). It was observed that, in 34 cases (42.25%) TRF2 expression was positive in tumour, while in 46 cases (57.75%), it was negative, while it was just reverse at CM, respectively. The odds of recurrence among patients having high levels of TRF2 in CM were 2.6 times higher than the odds of recurrence among patients having lower levels of TRF2 in CM. In conclusion, this study showed that TRF2 at surgical cut margin has a prognostic significance and can be used as a molecular marker for predicting survival in OSCC patients.
Literatur
1.
Zurück zum Zitat Sproll C, Fluegen G, Stoecklein NH (2018) Minimal Residual Disease in Head and Neck Cancer and Esophageal Cancer, in Biological Mechanisms of Minimal Residual Disease and Systemic Cancer, J.A. Aguirre-Ghiso, Editor, Springer International Publishing: Cham p 55-82 Sproll C, Fluegen G, Stoecklein NH (2018) Minimal Residual Disease in Head and Neck Cancer and Esophageal Cancer, in Biological Mechanisms of Minimal Residual Disease and Systemic Cancer, J.A. Aguirre-Ghiso, Editor, Springer International Publishing: Cham p 55-82
2.
Zurück zum Zitat Padhi S, Saha A, Kar M, Ghosh C, Adhya A, Baisakh M, Mohapatra N, Venkatesan S, Hande MP, Banerjee B (2015) Clinico-pathological correlation of β-catenin and telomere dysfunction in head and neck squamous cell carcinoma patients. J Cancer 6(2):192–202CrossRef Padhi S, Saha A, Kar M, Ghosh C, Adhya A, Baisakh M, Mohapatra N, Venkatesan S, Hande MP, Banerjee B (2015) Clinico-pathological correlation of β-catenin and telomere dysfunction in head and neck squamous cell carcinoma patients. J Cancer 6(2):192–202CrossRef
3.
Zurück zum Zitat Liu S-A, Wang CC, Jiang RS, Lee FY, Lin WJ, Lin JC (2017) Pathological features and their prognostic impacts on oral cavity cancer patients among different subsites - a singe institute's experience in Taiwan. Sci Rep 7(1):7451–7451CrossRef Liu S-A, Wang CC, Jiang RS, Lee FY, Lin WJ, Lin JC (2017) Pathological features and their prognostic impacts on oral cavity cancer patients among different subsites - a singe institute's experience in Taiwan. Sci Rep 7(1):7451–7451CrossRef
4.
Zurück zum Zitat Al-Swiahb JN et al (2010) Clinical, pathological and molecular determinants in squamous cell carcinoma of the oral cavity. Future Oncol 6(5):837–850CrossRef Al-Swiahb JN et al (2010) Clinical, pathological and molecular determinants in squamous cell carcinoma of the oral cavity. Future Oncol 6(5):837–850CrossRef
5.
Zurück zum Zitat Akhter M, et al. (2011) A study on histological grading of oral squamous cell carcinoma and its correlation with regional metastasis. Vol. 15. 168–76 Akhter M, et al. (2011) A study on histological grading of oral squamous cell carcinoma and its correlation with regional metastasis. Vol. 15. 168–76
6.
Zurück zum Zitat Viswanatha SC, Hedne N, Hasan S (2019) Correlation between histological grading, LVI and PNI of carcinoma oral tongue to lymph node metastasis. Int J Otorhinolaryngol Head Neck Surg 5(1):2018 Viswanatha SC, Hedne N, Hasan S (2019) Correlation between histological grading, LVI and PNI of carcinoma oral tongue to lymph node metastasis. Int J Otorhinolaryngol Head Neck Surg 5(1):2018
7.
Zurück zum Zitat Lin YT, Chien CY, Lu CT, Lou SD, Lu H, Huang CC, Fang FM, Li SH, Huang TL, Chuang HC (2015) Triple-positive pathologic findings in oral cavity cancer are related to a dismal prognosis. Laryngoscope 125(9):E300–E305CrossRef Lin YT, Chien CY, Lu CT, Lou SD, Lu H, Huang CC, Fang FM, Li SH, Huang TL, Chuang HC (2015) Triple-positive pathologic findings in oral cavity cancer are related to a dismal prognosis. Laryngoscope 125(9):E300–E305CrossRef
8.
Zurück zum Zitat Jardim JF, Francisco AL, Gondak R, Damascena A, Kowalski LP (2015) Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma. Int J Oral Maxillofac Surg 44(1):23–28CrossRef Jardim JF, Francisco AL, Gondak R, Damascena A, Kowalski LP (2015) Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma. Int J Oral Maxillofac Surg 44(1):23–28CrossRef
9.
Zurück zum Zitat Chen T-C, et al. (2013) The Impact of Perineural Invasion and/or Lymphovascular Invasion on the Survival of Early-Stage Oral Squamous Cell Carcinoma Patients. Vol. 20 Chen T-C, et al. (2013) The Impact of Perineural Invasion and/or Lymphovascular Invasion on the Survival of Early-Stage Oral Squamous Cell Carcinoma Patients. Vol. 20
10.
Zurück zum Zitat Huh JW, Lee JH, Kim HR, Kim YJ (2013) Prognostic significance of lymphovascular or perineural invasion in patients with locally advanced colorectal cancer. Am J Surg 206(5):758–763CrossRef Huh JW, Lee JH, Kim HR, Kim YJ (2013) Prognostic significance of lymphovascular or perineural invasion in patients with locally advanced colorectal cancer. Am J Surg 206(5):758–763CrossRef
11.
Zurück zum Zitat Al-Sukhni E et al (2017) Lymphovascular and perineural invasion are associated with poor prognostic features and outcomes in colorectal cancer: a retrospective cohort study. Int J Surg 37:42–49CrossRef Al-Sukhni E et al (2017) Lymphovascular and perineural invasion are associated with poor prognostic features and outcomes in colorectal cancer: a retrospective cohort study. Int J Surg 37:42–49CrossRef
12.
Zurück zum Zitat Feuerhahn S, Chen LY, Luke B, Porro A (2015) No DDRama at chromosome ends: TRF2 takes Centre stage. Trends Biochem Sci 40(5):275–285CrossRef Feuerhahn S, Chen LY, Luke B, Porro A (2015) No DDRama at chromosome ends: TRF2 takes Centre stage. Trends Biochem Sci 40(5):275–285CrossRef
13.
Zurück zum Zitat Mao Z et al (2007) TRF2 is required for repair of nontelomeric DNA double-strand breaks by homologous recombination. Proc Natl Acad Sci U S A 104(32):13068–13073CrossRef Mao Z et al (2007) TRF2 is required for repair of nontelomeric DNA double-strand breaks by homologous recombination. Proc Natl Acad Sci U S A 104(32):13068–13073CrossRef
14.
Zurück zum Zitat Tanaka H, et al. (2005) DNA damage-induced phosphorylation of the human telomere-associated protein TRF2, in Proc Natl Acad Sci U S A. p. 15539–44 Tanaka H, et al. (2005) DNA damage-induced phosphorylation of the human telomere-associated protein TRF2, in Proc Natl Acad Sci U S A. p. 15539–44
15.
Zurück zum Zitat Diala I, Wagner N, Magdinier F, Shkreli M, Sirakov M, Bauwens S, Schluth-Bolard C, Simonet T, Renault VM, Ye J, Djerbi A, Pineau P, Choi J, Artandi S, Dejean A, Plateroti M, Gilson E (2013) Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway. EMBO Rep 14(4):356–363CrossRef Diala I, Wagner N, Magdinier F, Shkreli M, Sirakov M, Bauwens S, Schluth-Bolard C, Simonet T, Renault VM, Ye J, Djerbi A, Pineau P, Choi J, Artandi S, Dejean A, Plateroti M, Gilson E (2013) Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway. EMBO Rep 14(4):356–363CrossRef
16.
Zurück zum Zitat Saha A, Padhi S, Kar M, Roy S, Maiti P, Banerjee B (2017) Role of TRF2 in efficient DNA repair, spheroid formation and Cancer Stem Cell maintenance. Oncomedicine 2:71–79CrossRef Saha A, Padhi S, Kar M, Roy S, Maiti P, Banerjee B (2017) Role of TRF2 in efficient DNA repair, spheroid formation and Cancer Stem Cell maintenance. Oncomedicine 2:71–79CrossRef
17.
Zurück zum Zitat Canene-Adams K (2013) Chapter Fifteen - Preparation of Formalin-fixed Paraffin-embedded Tissue for Immunohistochemistry, in Methods in Enzymology, J. Lorsch, Editor, Academic Press. p. 225–233 Canene-Adams K (2013) Chapter Fifteen - Preparation of Formalin-fixed Paraffin-embedded Tissue for Immunohistochemistry, in Methods in Enzymology, J. Lorsch, Editor, Academic Press. p. 225–233
18.
Zurück zum Zitat Ashmead MG (2013) Malignant Neoplasms of the Oral Cavity, in Encyclopedia of Otolaryngology, Head and Neck Surgery, S.E. Kountakis, Editor, Springer Berlin Heidelberg: Berlin, Heidelberg p 1558-1567 Ashmead MG (2013) Malignant Neoplasms of the Oral Cavity, in Encyclopedia of Otolaryngology, Head and Neck Surgery, S.E. Kountakis, Editor, Springer Berlin Heidelberg: Berlin, Heidelberg p 1558-1567
19.
Zurück zum Zitat Li G et al (2017) Prediction of biomarkers of oral squamous cell carcinoma using microarray technology. Sci Rep 7:42105CrossRef Li G et al (2017) Prediction of biomarkers of oral squamous cell carcinoma using microarray technology. Sci Rep 7:42105CrossRef
20.
Zurück zum Zitat Pedro NF et al (2018) Candidate biomarkers for Oral squamous cell carcinoma: differential expression of oxidative stress-related genes. Asian Pac J Cancer Prev 19(5):1343–1349PubMedPubMedCentral Pedro NF et al (2018) Candidate biomarkers for Oral squamous cell carcinoma: differential expression of oxidative stress-related genes. Asian Pac J Cancer Prev 19(5):1343–1349PubMedPubMedCentral
21.
Zurück zum Zitat Wang R, Yuan Y, Zhou Y, Zhang D, Zhang L, Zeng X, Ji N, Zhou M, Liang X, Chen Y, Geng N, Li J, Chen Q (2018) Screening diagnostic biomarkers of OSCC via an LCM-based proteomic approach. Oncol Rep 40(4):2088–2096PubMed Wang R, Yuan Y, Zhou Y, Zhang D, Zhang L, Zeng X, Ji N, Zhou M, Liang X, Chen Y, Geng N, Li J, Chen Q (2018) Screening diagnostic biomarkers of OSCC via an LCM-based proteomic approach. Oncol Rep 40(4):2088–2096PubMed
22.
Zurück zum Zitat Saha A et al (2018) Role of Telomeric TRF2 in Orosphere formation and CSC phenotype maintenance through efficient DNA repair pathway and its correlation with recurrence in OSCC. Stem Cell Rev Rep 14(6):871–887CrossRef Saha A et al (2018) Role of Telomeric TRF2 in Orosphere formation and CSC phenotype maintenance through efficient DNA repair pathway and its correlation with recurrence in OSCC. Stem Cell Rev Rep 14(6):871–887CrossRef
23.
Zurück zum Zitat Nakanishi K, Kawai T, Kumaki F, Hiroi S, Mukai M, Ikeda E, Koering CE, Gilson E (2003) Expression of mRNAs for telomeric repeat binding factor (TRF)-1 and TRF2 in atypical adenomatous hyperplasia and adenocarcinoma of the lung. Clin Cancer Res 9:1105–1111PubMed Nakanishi K, Kawai T, Kumaki F, Hiroi S, Mukai M, Ikeda E, Koering CE, Gilson E (2003) Expression of mRNAs for telomeric repeat binding factor (TRF)-1 and TRF2 in atypical adenomatous hyperplasia and adenocarcinoma of the lung. Clin Cancer Res 9:1105–1111PubMed
24.
Zurück zum Zitat Miyachi K, Fujita M, Tanaka N, Sasaki K, Sunagawa M (2002) Correlation between telomerase activity and telomeric-repeat binding factors in gastric cancer. J Exp Clin Cancer Res 21:269–275PubMed Miyachi K, Fujita M, Tanaka N, Sasaki K, Sunagawa M (2002) Correlation between telomerase activity and telomeric-repeat binding factors in gastric cancer. J Exp Clin Cancer Res 21:269–275PubMed
25.
Zurück zum Zitat Pal D, Sharma U, Singh SK, Kakkar N, Prasad R (2015) Over-expression of telomere binding factors (TRF1 & TRF2) in renal cell carcinoma and their inhibition by using SiRNA induce apoptosis, reduce cell proliferation and migration invitro. PLoS One 10:e0115651CrossRef Pal D, Sharma U, Singh SK, Kakkar N, Prasad R (2015) Over-expression of telomere binding factors (TRF1 & TRF2) in renal cell carcinoma and their inhibition by using SiRNA induce apoptosis, reduce cell proliferation and migration invitro. PLoS One 10:e0115651CrossRef
26.
Zurück zum Zitat Ozden S, Tiber PM, Ozgen Z, Ozyurt H, Serakinci N, Orun O (2014) Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients. Biol Res 47(1):61CrossRef Ozden S, Tiber PM, Ozgen Z, Ozyurt H, Serakinci N, Orun O (2014) Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients. Biol Res 47(1):61CrossRef
27.
Zurück zum Zitat Ning H, Li T, Zhao L, Li T, Li J, Liu J, Liu Z, Fan D (2006) TRF2 promotes multidrug resistance in gastric cancer cells. Cancer Biol Ther 5(8):950–956CrossRef Ning H, Li T, Zhao L, Li T, Li J, Liu J, Liu Z, Fan D (2006) TRF2 promotes multidrug resistance in gastric cancer cells. Cancer Biol Ther 5(8):950–956CrossRef
28.
Zurück zum Zitat Benhamou Y et al (2016) Telomeric repeat-binding factor 2: A marker for survival and anti-EGFR efficacy in oral carcinoma. Oncotarget 7(28):44236–44251CrossRef Benhamou Y et al (2016) Telomeric repeat-binding factor 2: A marker for survival and anti-EGFR efficacy in oral carcinoma. Oncotarget 7(28):44236–44251CrossRef
29.
Zurück zum Zitat Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674CrossRef Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674CrossRef
30.
Zurück zum Zitat Mitra A, Mishra L, Li S (2015) EMT, CTCs and CSCs in tumor relapse and drug-resistance. Oncotarget 6:10697–10711CrossRef Mitra A, Mishra L, Li S (2015) EMT, CTCs and CSCs in tumor relapse and drug-resistance. Oncotarget 6:10697–10711CrossRef
Metadaten
Titel
TRF2 Overexpression at the Surgical Resection Margin: A Potential Predictive Biomarker in Oral Squamous Cell Carcinoma for Recurrence
verfasst von
Madhabananda Kar
Mahesh Sultania
Souvick Roy
Swatishree Padhi
Birendranath Banerjee
Publikationsdatum
19.02.2020
Verlag
Springer India
Erschienen in
Indian Journal of Surgical Oncology / Ausgabe Sonderheft 1/2021
Print ISSN: 0975-7651
Elektronische ISSN: 0976-6952
DOI
https://doi.org/10.1007/s13193-020-01042-5

Weitere Artikel der Sonderheft 1/2021

Indian Journal of Surgical Oncology 1/2021 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

CME: 2 Punkte

Prof. Dr. med. Gregor Antoniadis Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

CME: 2 Punkte

Dr. med. Benjamin Meyknecht, PD Dr. med. Oliver Pieske Das Webinar S2e-Leitlinie „Distale Radiusfraktur“ beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

CME: 2 Punkte

Dr. med. Mihailo Andric
Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.