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VOLUME 23 , ISSUE 5 ( May, 2022 ) > List of Articles


Association of Stathmin (Op18) with TNM Staging and Grading of Oral Squamous Cell Carcinoma and Its Role in Tumor Progression

Purnima Vadla, Gaddam Deepthi, Vaishnavi Julakanti, Divya Jahagirdar, Swetha Meruva, Swapnika Tantravahi

Keywords : Biomarker, Leukoplakia, Oral squamous cell carcinoma, Prognosis, Stathmin

Citation Information : Vadla P, Deepthi G, Julakanti V, Jahagirdar D, Meruva S, Tantravahi S. Association of Stathmin (Op18) with TNM Staging and Grading of Oral Squamous Cell Carcinoma and Its Role in Tumor Progression. J Contemp Dent Pract 2022; 23 (5):497-502.

DOI: 10.5005/jp-journals-10024-3342

License: CC BY-NC 4.0

Published Online: 10-08-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Aim: The purpose of the study was to evaluate the expression of stathmin in different histological grades and tumor, node, metastasis (TNM) staging of Oral carcinoma and various grades of oral dysplasia. The study also aims at observing the stathmin expression with respect to lymph node metastasis. Materials and methods: A total of 90 histopathologically confirmed tissue sections were acquired, of which 30 sections of oral dysplasia, 30 oral squamous cell carcinoma (OSCC) and 30 normal tissue sections were stained immunohistochemically with stathmin. The tissue sections, were categorized into different grades of oral dysplasia and OSCC based on histopathological examination. For estimation of stathmin expression, manual examination of 300 cells was done in a minimum of five different areas of tissue section and a mean proportion of positive-stained cells were determined. The statistical analysis of the results was done using ANOVA test. Results: A statistically significant increase in mean staining scores of stathmin in OSCC group compared to dysplasia and control groups. A statistically significant difference was observed in different grades of dysplasia and OSCC groups. Stage III and stage IV OSCC tissue sections showed high intensity staining scores of stathmin expression. Conclusion: An increased expression of stathmin was detected in various grades of OSCC and also with respect to staging of oral cancer. Half the cases of OSCC with lymph node metastasis showed high intensity scores of stathmin. Based on the above facts, stathmin expression was indicated as a potential tool for predicting the outcome of oral cancer patients with lymph node metastasis and its expression was increased in the group with poor prognosis. Clinical significance: Any damage/mutation to stathmin can result in defects in cell division resulting in aneuploidy and in turn cancers. In this study, the results showed that there is a differential expression of stathmin in the early and the advanced grades and different TNM stages of OSCC. A high expression of stathmin was observed in all the cases with lymph node metastasis. These observations prove that stathmin has an important role in the progression, tumorigenicity, and prognosis of the oral cancer.

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  1. Hailat N, Strahler JR, Melhem RF, et al. N-myc gene amplification in neuroblastoma is associated with altered phosphorylation of a proliferation related polypeptide (Op 18). Oncogene 1990;5(11):1615–1618. PMID: 2267130.
  2. Tian X, Tian Y, Sarich N, et al. Novel role of stathmin in microtubule-dependent control of endothelial permeability. FASEB J 2013;26(9):3862–3874. DOI: 10.1096/fj.12-207746.
  3. Sobel A. Stathmin: A relay phosphoprotein for multiple signal transduction? Trends Biochem Sci 1991;16:301–305. DOI: 10.1016/0968-0004(91)90123-d.
  4. Rubin CI, Atweh GF. The role of stathmin in the regulation of the cell cycle. J Cell Biochem 2004;93(2):242–250. DOI: 10.1002/jcb.20187.
  5. Liu F, Sun YL, Xu Y, et al. Expression and phosphorylation of stathmin correlate with cell migration in esophageal squamous cell carcinoma. Oncol Rep 2013;29(2):419–424. DOI: 10.3892/or.2012.2157.
  6. Brattsand G. Correlation of oncoprotein 18/stathmin expression in human breast cancer with established prognostic factors. Br J Cancer 2000;83(3):311–318. DOI: 10.1054/bjoc.2000.1264.
  7. Trovik J, Wik E, Stefansson IM, et al. Stathmin overexpression identifies high risk patients and lymph node metastasis in endometrial cancer. Clin Cancer Res 2011;17(10):3368–3377. DOI: 10.1158/1078-0432.CCR-10-2412.
  8. Hsieh SY, Huang SF, Yu MC, et al. Stathmin1 overexpression associated with polyploidy, tumor-cell invasion, early recurrence, and poor prognosis in human hepatoma. Mol Carcinog 2010;49(5):476–487.
  9. Zheng P, Liu YX, Chen L, et al. Stathmin, a new target of PRL-3 identified by proteomic methods, plays a key role in progression and metastasis of colorectal cancer. J Proteome Res 2010;9(10):4897–4905. DOI: 10.1021/pr100712t.
  10. Varambally S, Yu J, Laxman B, et al. Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell 2005;8(5):393–406. DOI: 10.1016/j.ccr.2005.10.001.
  11. Alaiya AA, Franzen B, Fujioka K, et al. Phenotypic analysis of ovarian carcinoma: polypeptide expression in benign, borderline and malignant tumors. Int J Cancer 1997;73(5):678–683. DOI: 10.1002/(sici)1097-0215(19971127)73:5<678::aid-ijc11>;2-2.
  12. Karst AM, Levanon K, Duraisamy S, et al. Stathmin 1, a marker of PI3K pathway activation and regulator of microtubule dynamics, is expressed in early pelvic serous carcinomas. Gynecol Oncol 2011;123(1):5–12. DOI: 10.1016/j.ygyno.2011.05.021.
  13. Fleskens S, Slootweg P. The histological grading of oral leukoplakia was done based on World Health Organization criteria. Grading systems in head and neck dysplasia: Their prognostic value, weaknesses and utility. Head Neck Oncol 2009;1(1):11–19. DOI: 10.1186/1758-3284-1-11.
  14. Broders AC. The microscopic grading of cancer. Surg Clin North Am 1941;21:947–962.
  15. Belletti B, Baldassarre G. Stathmin: A protein with many tasks. New biomarker and potential target in cancer. Expert Opin Ther Targets 2011;15(11):1249–1266. DOI: 10.1517/14728222.2011.620951.
  16. Biaoxue R, Xiguang C, Hua L, et al. Stathmin-dependent molecular targeting therapy for malignant tumor: The latest 5 years’ discoveries and developments. J Transl Med 2016;14(1):279. DOI: 10.1186/s12967-016-1000-z.
  17. Rowlands DC, Williams A, Jones NA, et al. Stathmin expression is a feature of proliferating cells of most, if not all, cell lineages. Lab Invest 1995;72(1):100–113. PMID: 7837783.
  18. Alli E, Yang JM, Hait WN. Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. Oncogene 2007;26(7):1003–1012. DOI: 10.1038/sj.onc.1209864.
  19. Yuan RH, Jeng YM, Chen HL, et al. Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma. J Pathol 2006;209(4):549–558. DOI: 10.1002/path.2011.
  20. Khan W, Augustine D, Rao RS, et al. Stem cell markers SOX-2 and OCT-4 enable to resolve the diagnostic dilemma between ameloblastic carcinoma and aggressive solid multicystic ameloblastoma. Adv Biomed Res 2018;7:149. DOI: 10.4103/abr.abr_135_18. eCollection 2018.
  21. Augustine D, Sekar B, Murali S, et al. Expression of inducible nitric oxide synthase in carcinomas and sarcomas affecting the oral cavity. South Asian J Cancer 2015;4(2):78–82. DOI: 10.4103/2278-330X.155686.
  22. Singh P, Augustine D, Rao RS, et al. Interleukin-1beta and caspase-3 expression serve as independent prognostic markers for metastasis and survival in oral squamous cell carcinoma. Cancer Biomark 2019;26(1):109–122. DOI: 10.3233/CBM-190149.
  23. Wang S, Akhtar J, Wang Z. Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma. Tumour Biol 2015;36(10):7797–7806. DOI: 10.1007/s13277-015-3520-1.
  24. Lu Y, Liu C, Cheng H, et al. Stathmin, interacting with Nf-kappaB, promotes tumor growth and predicts poor prognosis of pancreatic cancer. Curr Mol Med 2014;14(3):328–339. DOI: 10.2174/1566524014666140228120913.
  25. Nie W, Xu MD, Gan L, et al. Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer. Lab Invest 2015;95(1):56–64. DOI: 10.1038/labinvest.2014.124.
  26. Berton S, Pellizzari I, Fabris L, et al. Genetic characterization of p27 (kip1) and stathmin in controlling cell proliferation in vivo. Cell Cycle 2014;13(19):3100–3111. DOI: 10.4161/15384101.2014.949512.
  27. Askeland C, Wik E, Finne K, et al. Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups. Sci Rep 2020;10(1):2914. DOI: 10.1038/s41598-020-59728-3.
  28. Jia, W, Lin Z, Wen J, et al. SEPTIN2 and STATHMIN regulate CD99-mediated cellular differentiation in Hodgkin's lymphoma. PLOS One 2015;10(5):e0127568. DOI: 10.1371/journal.pone.0127568.
  29. Price DK, Ball JR, Bahrani–Mostafavi Z, et al. The phosphoprotein Op18/stathmin is differentially expressed in ovarian cancer. Cancer Invest 2000;18(8):722–730. DOI: 10.3109/07357900009012204.
  30. Takahashi M, Yang XJ, Lavery TT, et al. Gene expression profiling of favorable histology Wilms tumors and its correlation with clinical features. Cancer Res 2002;62(22):6598–6605. PMID: 12438255.
  31. Nakashima D, Uzawa K, Kasamatsu A, et al. Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands. Int J Cancer 2005;118(3):704–713. DOI: 10.1002/ijc.21318.
  32. Kouzu Y, Uzawa K, Koike H, et al. Overexpression of stathmin in oral squamous cell carcinoma: correlation with tumour progression and poor prognosis. Br J Cancer 2006;94(5):717–723. DOI: 10.1038/sj.bjc.6602991.
  33. Cheng AL, Huang WG, Chen ZC, et al. Identification of novel nasopharyngeal carcinoma biomarkers by laser capture microdissection and proteomic analysis. Clin Cancer Res 2008;14(2):435–445. DOI: 10.1158/1078-0432.CCR-07-1215.
  34. Jeon TY, Han ME, Lee YW, et al. Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells. Br J Cancer 2010;102(4):710–718. DOI: 10.1038/sj.bjc.6605537.
  35. Oishi Y, Nagasaki K, Miyata S, F et al. Functional pathway characterized by gene expression analysis of supraclavicular lymph node metastasis-positive breast cancer. J Hum Genet 2007;52(3):271–279. DOI: 10.1007/s10038-007-0111-z.
  36. Marafioti T, Copie–Bergman C, Calaminici M, et al. Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups. Histopathology 2013;62(6):860–875.
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