The prognostic role of immunohistochemical markers in surgical margins of Indian patients with oral squamous cell carcinoma- a retrospective study protocol
Background: Positive surgical margins in oral squamous cell carcinoma (OSCC) is an important predictor of recurrence. Unfortunately, recurrence is found in cases with negative surgical margins as well and hence molecular markers are being investigated to identify the tumor cells in negative surgical margins to improve the survival of patients. The study aimed to ascertain the prognostic role of p53, eIF4E and E-cadherin in negative surgical margins and association of their expression with clinical parameters, recurrence, and survival.
Methods: India based retrospective cohort study of patients who were surgically treated for OSCC between 2011 and 2014. Thirty patients with negative surgical margins were assessed for this study. Sixty-four negative surgical margins were evaluated using immunohistochemistry with monoclonal mouse p53, monoclonal rabbit eIF4E and monoclonal mouse E-cadherin antibodies.
Results: Fisher’s exact test, Fishers Freeman Halton exact test and contingency tables were used to assess the association between recurrence rate and clinicopathologic parameters also any association with the expression of p53, eIF4E and E-cadherin in the surgical margins and each patients’ clinical characteristics. ANOVA (analysis of variance) was used to assess the role of clinicopathologic parameters in survival of the patients. The sensitivity and specificity of each antibody along with positive and negative predictive values were calculated. Kaplan Meier was used for analysis of recurrence and five-year survival. P<0.05 was used to denote a statistically significant difference.
Conclusion: This study could help in identification of patients with minimal residual cancer in the surgical margins and might help in better therapeutic management to improve survival of OSCC patients.
Sharma S, Satyanarayana L, Asthana S, Shivalingesh K, Goutham BS, Ramachandra S. Oral cancer statistics in India on the basis of first report of 29 population-based cancer registries. J Oral Maxillofac Pathol. 2018;22:18-26.
Taghavi N, Yazdi I. Prognostic factors of survival rate in oral squamous cell carcinoma: Clinical, histologic, genetic and molecular concepts. Arch Iran Med. 2015;18:314-9.
Stathopoulos P, Smith WP. Close Resection Margins Do Not Influence Local Recurrence in Patients with Oral Squamous Cell Carcinoma: A Prospective Cohort Study. J Oral Maxillofac Surg. 2018;76:873-6.
Stathopoulos P, Smith PW. Analysis of survival rates following primary surgery of 178 consecutive patients with oral cancer in a large district general hospital. J Maxillofac Oral Surg. 2017;16:158.
Sutton DN, Brown JS, Rogers SN, Vaughan ED, Woolgar JA. The prognostic implications of the surgical margin in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2003;32:30.
Tasche KK, Buchakjian MR, Pagedar NA, Sperry SM. Definition of "Close Margin" in Oral Cancer Surgery and Association of Margin Distance with Local Recurrence Rate. JAMA Otolaryngol Head Neck Surg. 2017;143:1166-72.
Braakhuis BJ, Bloemena E, Leemans CR, Brakenhoff RH. Molecular analysis of surgical margins in head and neck cancer: more than a marginal issue. Oral Oncol. 2010;46:485-91.
Ranka R, Chaudhary M, Sharma P. Role of Immunohistochemical Markers in Surgical Margins of Patients with Head and Neck Carcinoma-A Systematic Review. Int J Cur Res Rev. 2020;12:9-17.
Roncella S, Ferro P, Bacigalupo B, Tognoni A, Falco E, Gianquinto D et al. Human mammaglobin mRNA is a reliable molecular marker for detecting occult breast cancer cells in peripheral blood. J Exp Clin Cancer Res. 2005;24:265-71.
Brennan JA, Mao L, Hruban RH, Boyle JO, Eby YJ, Koch WM, et al. Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck. N Engl J Med. 1995;332:429-35.
Van Houten VM, Leemans CR, Kummer JA, Dijkstra J, Kuik DJ, van den Brekel MW et al. Molecular diagnosis of surgical margins and local recurrence in head and neck cancer patients: a prospective study. Clin Cancer Res. 2004;10:3614-20.
Huang X, Pateromichelakis S, Hills A, Sherriff M. p53 mutations in deep tissues are more strongly associated with recurrence than mutation positive mucosal margins. Clin Cancer Res. 2017;13:6099-106.
Singh J, Jayaraj R, Baxi S, Mileva M, Skinner J et al. Immunohistochemical expression levels of p53 and eIF4E markers in histologically negative surgical margins, and their association with the clinical outcome of patients with head and neck squamous cell carcinoma. Mol Clin Oncol. 2016;4:166-72.
Han M, Wang W, Wang L, Jiang Y. Expression of eukaryotic initiation factor 4 E in hypopharyngeal carcinoma. J Int Med Res. 2014;42:976-83.
Culjkovic B, Borden KL. Understanding and Targeting the Eukaryotic Translation Initiation Factor eIF4E in Head and Neck Cancer. J Oncol. 2009;2009:981679.
Wang XL, Cai HP, Ge JH, Su XF. Detection of eukaryotic translation initiation factor 4E and its clinical significance in hepatocellular carcinoma. World J Gastroenterol. 2012;18:2540-4.
Nathan CO, Liu L, Li BD, Abreo FW. Detection of the proto-oncogene eIF4E in surgical margins may predict recurrence in head and neck cancer. Oncogene. 1997;15:579-84.
Bengallo T, El-Faitori M, Sassi S, Khaial FB, El Gehani K, Buhmeida A et al. Expression of E-Cadherin in Prostatic Carcinoma: Prognostic Significance. J Cancer Prev Curr Res. 2016;4:00119.
Efstathiou JA, Liu D, Wheeler JM, Beck NE, Ilyas M, Karayiannakis AJ et al. Mutated epithelial cadherin is associated with increased tumorigenicity and los of adhesion and of responsiveness to the motogenic trefoil factor 2 in colon carcinoma cells. Proc Natl Acad Sci USA. 1999;96:2316-21.
Mohtasham N, Anvari K, Memar B, Saghravanian N, Ghazi N, Bagherpour A et al. Expression of E-cadherin and matrix metalloproteinase-9 in oral squamous cell carcinoma and histologically negative surgical margins and association with clinicopathological parameters. Rom J Morphol Embryol. 2014;55:117-21.
Waitzberg AF, Nonogaki S, Nishimoto IN, Kowalski LP, Miguel RE, Brentani RR et al. Clinical significance of c-myc and p53 expression in head and neck squamous cell carcinomas. Cancer Detect Prev. 2004;28:178-86.
Nathan CAO, Sanders K, Abreo FW, Nassar R, Glass J. Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: prognostic implications. Cancer Res. 2000;60:3599.
Ogbureke KU, Weinberger PM, Looney SW, Li L, Fisher LW. Expressions of matrix metalloproteinase-9 (MMP-9), dentin sialophosphoprotein (DSPP), and osteopontin (OPN) at histo¬logically negative surgical margins may predict recurrence of oral squamous cell carcinoma. Oncotarget. 2012;3:286-98.