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Indian Journal of Otolaryngology and Head & Neck Surgery
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26-07-2023 | Original Article

p53, Cytokeratin 19 Expression in Oral Squamous Cell Carcinoma and Correlation with Histopathologic Grading: An Immunohistochemical Study

Authors: Harpreet Kaur, Vinay Hazarey, Gitika Sharma, Suchitra Gosavi, Rana AGK Pal, Vandana Gupta

Published in: Indian Journal of Otolaryngology and Head & Neck Surgery | Issue 1/2024

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Abstract

The purpose of this study was to examine the immunohistochemical expression of p53 and cytokeratin 19 (CK19) in normal oral mucosa (NOM) and oral squamous cell carcinoma (OSCC) and their association with histopathological differentiation grade. The secondary goal was to see if there was any correlation between p53 and CK19 expression in NOM and OSCC. A hospital-based retrospective analysis was conducted in which 40 NOM and 45 OSCC samples were acquired from archives and stained with mouse monoclonal antibodies p53 and CK19. For both the NOM and OSCC groups, the proportion of positively stained cells, staining intensity, and staining index were calculated. p53 immunoexpression revealed that 85% of positively stained cells in the NOM basal layer had a low staining index (mean ± SD 1.87 ± 0.34), whereas 66.7% of positively stained cells in the OSCC had a high staining index (mean ± SD 5.63 ± 3.02). When NOM and OSCC were compared, there was a statistically significant difference in staining intensity. However, despite a linear increase in the percentage of positive cells from well to poorly differentiated, the comparison between histopathological grades was non-significant. CK19 exhibited 18.5% positively stained cells in the NOM basal layer with a low staining index (mean ± SD 1.57 ± 0.53), whereas OSCC samples showed 4.44% immunopositivity with a high staining index. p53 is a marker of oral carcinogenesis independent of histological grade and CK19 expression. Further, CK19 is a marker of dysfunctional epithelial differentiation but lacks sensitivity and specificity; however, it demands further multicentric studies with a large sample size to draw definitive conclusions.
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Literature
1.
2.
Gupta B, Johnson NW, Kumar N (2016) Global epidemiology of head and neck cancers: a continuing challenge. Oncology 91:13–23PubMedCrossRef
3.
Johnson NW (1991) Orofacial neoplasms: global epidemiology, risk factors and recommendations for research. Int Dent J 41:365–375PubMed
4.
Funk GF, Karnell LH, Robinson RA, Zen WK, Trask DK, Hoffman HT (2002) Presentation, treatment and outcome of oral cavity cancer: a national cancer data data base report. Head Neck 24:165–180PubMedCrossRef
5.
Platz H, Fries R, Fries R, Hudec M (1985) Retrospective DOSAK study on carcinomas of the oral cavity: results and consequences. J Maxillofac Surg 13:147–153PubMedCrossRef
6.
Snow GB, Patel P, Leemans CR, Tiwari R (1992) Management of cervical lymph nodes in patients with head and neck cancer. Eur Arch Otorhinolaryngol 249:187–194PubMedCrossRef
7.
Yamamoto E, Miyakawa A, Kohama G (1984) Mode of invasion and lymph node metastasis in squamous cell carcinoma of the oral cavity. Head Neck Surg 6:938–947PubMedCrossRef
8.
Almangush A, Mäkitie AA, Triantafyllou A, de Bree R, Strojan P, Rinaldo A, Hernandez-Prera JC, Suárez C, Kowalski LP, Ferlito A, Leivo I (2020) Staging and grading of oral squamous cell carcinoma: An update. Oral oncology. Aug 1;107:104799
9.
Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24PubMedCrossRef
10.
Moll R, Krepler R, Franke WW (1983) Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation 23:256–269PubMedCrossRef
11.
Wu YJ, Rheinwald JG (1981) A new small (40 kd) keratin filament protein made by some cultured human squamous cell carcinomas. Cell 25:627–635PubMedCrossRef
12.
Sugama Y, Kitamura S, Kawai T, Ohkubo A, Hasegawa S, Kuriyama T et al (1994) Clinical usefulness of CYFRA assay in diagnosing lung cancer: measurement of serum cytokeratin fragment. Jpn J Cancer Res 85:1178–1184PubMedPubMedCentralCrossRef
13.
Wieskopf B, Demangeat C, Purohit A, Strenger R, Gries P, Kreisman H et al (1995) Cyfa21- 1 as a biologic marker of non-small cell lung cancer. Chest 108:163–169PubMedCrossRef
14.
Takahashi H, Kurishima K, Ishikawa H (2010) Optimal cutoff points of CYFRA21-1 for survival prediction in non‐small cell lung cancer patients based on running statistical analysis. Anticancer Res 30:3833–3837PubMed
15.
Khanna R, Vidhyarthi AK, Khanna S, Singh S, Singh UC (2012) Expression of p53 protein in Leukoplakia and oral squamous cell carcinoma. World J Surg Med Radiation Oncol 1:16
16.
Hamakawa H, Bao Y, Takarada M, Fukuzumi M, Tanioka H (1998) Cytokeratin expression in squamous cell carcinoma of the lung and oral cavity: an immunohistochemical study with possible clinical relevance. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:438–443PubMedCrossRef
17.
Nylander K, Dabelsteen E, Hall PA (2000) The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck. J Oral Pathol Med 29:413–425PubMedCrossRef
18.
Abrahao AC, Bonelli BV, Nunes FD, Dias EP, Cabral MG (2011) Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders. Braz Oral Res 25:34–41PubMedCrossRef
19.
Li L, Fukumoto M, Liu D (2013) Prognostic significance of p53 immunoexpression in the survival of oral squamous cell carcinoma patients treated with surgery and neoadjuvant chemotherapy. Oncol Lett 6(1):1611–1615PubMedPubMedCentralCrossRef
20.
Cui XS, Donehower LA (2000 Dec) Differential gene expression in mouse mammary adenocarcinomas in the presence and absence of wild type p53. Oncogene 19:5988–5996
21.
Kale AD, Mane DR, Babji D, Gupta K (2012) Establishment of field change by expression of cytokeratins 8/18, 19, and MMP-9 in an apparently normal oral mucosa adjacent to squamous cell carcinoma: a immunohistochemical study. J Oral Maxillofac Pathol 16:10–15PubMedPubMedCentralCrossRef
22.
Safadi RA, Musleh AS, Al-Khateeb TH, Hamasha AA (2010) Analysis of immunohistochemical expression of k19 in oral epithelial dysplasia and oral squamous cell carcinoma using color deconvolution-image analysis method. Head Neck Pathol 4:282–289PubMedPubMedCentralCrossRef
23.
Rao RS, Patil S, Ganavi BS Oral cytokeratins in health and disease. J Contemp Dent Pract. 2014 Jan 1;15(1):127 – 36
24.
Lindberg K, Rheinwald JG (1989) Suprabasal 40 kd keratin (K19) expression as an immunohistologic marker of premalignancy in oral epithelium. Am J Pathol 134:89PubMedPubMedCentral
25.
Babiker AY, Rahmani AH, Abdalaziz MS, Albutti A, Aly SM, Ahmed HG (2014) Expressional analysis of p16 and cytokeratin19 protein in the genesis of oral squamous cell carcinoma patients. Int J Clin Exp Med 7:1524–1530PubMedPubMedCentral
26.
Vora HH, Shah NG, Patel DD, Trivedi TI, Chikhlikar PR (2003) Prognostic significance of biomarkers in squamous cell carcinoma of the tongue: multivariate analysis. J Surg Oncol 82:34–50PubMedCrossRef
27.
Frohwitter G, Buerger H, Van Diest PJ, Korsching E, Kleinheinz J, Fillies T (2016) Cytokeratin and protein expression patterns in squamous cell carcinoma of the oral cavity provide evidence for two distinct pathogenetic pathways. Oncol Lett 12:107–113PubMedPubMedCentralCrossRef
28.
Fillies T, Jogschies M, Kleinheinz J, Brandt B, Joos U, Buerger H (2007) Cytokeratin alteration in oral leukoplakia and oral squamous cell carcinoma. Oncol Rep 18:639–643PubMed
29.
Crowe DL, Milo GE, Shuler CE (1999) Keratin 19 downregulation by oral squamous cell carcinoma lines increases invasive potential. J Dent Res 78:1256–1263PubMedCrossRef
30.
Molès JP, Schiller JT, Tesniere A, Leigh IM, Guilhou JJ, Basset-Séguin N (1994) Analysis of HPV16 E6 and mutant p53-transfected keratinocytes in reconstituted epidermis suggests that wild-type p53 inhibits cytokeratin 19 expression. J Cell Sc 107:435–441CrossRef
31.
Soussi T (2000) The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann N Y Acad Sci 910:121–139ADSPubMedCrossRef
32.
Oliveira LR, Ribeiro-Silva A (2011) Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 40:298–307PubMedCrossRef
33.
Bhargava A, Saigal S, Chalishazar M (2010) Histopathological grading systems in oral squamous cell carcinoma: a review. J Int Oral Health 2:1–10
34.
Etemad-Moghadam S, Khalili M, Tirgary F, Alaeddin M (2009) Evaluation of myofibroblasts in oral epithelial dysplasia and squamous cell carcinoma. J Oral Pathol 38:625–643CrossRef
35.
Kumar Shukla N, Deo SS, Jakhetiya A, Manjunath NM, Sreenivas V, Thulkar S et al (2018) Clinical spectrum, treatment and relapse patterns in 353 patients with squamous cell carcinoma of the Alveobuccal Complex treated with a curative intent: a retrospective study. J Maxillofac Oral Surg 17:24–31CrossRef
36.
Ries JC, Schreiner D, Steininger H, Girod SC (1998) p53 mutation and detection of p53 protein expression in oral leukoplakia and oral squamous cell carcinoma. Anticancer Res 18(3B):2031–2036PubMed
37.
Verma R, Singh A, Jaiswal R, Chandra A, Verma R, Tak J (2014) Association of Ki 67 antigen and p53 protein at invasive tumor front of oral squamous cell carcinoma. Indian J Pathol Microbiol 57:553–557PubMedCrossRef
38.
Montebugnoli L, Felicetti L, Gissi DB, Cervellati F, Servidio D, Marchetti C et al (2008) Predictive role of p53 protein as a single marker or associated to Ki67 antigen in oral carcinogenesis. Open Dent J 2:24–29PubMedPubMedCentralCrossRef
39.
Bidaud P, Chasle J, Sichel F, Rousseau S, Petit P, Pottier D et al (2010) Expression of p53 family members and CD44 in oral squamous cell carcinoma (OSCC) in relation to tumorigenesis. Histol Histopathol 25:331–339PubMed
40.
Yang L, Wang Y, Guo L, Wang L, Chen W, Shi B (2015) The expression and correlation of iNOS and p53 in oral squamous cell carcinoma. Biomed Res Int. ; 2015: 637853
41.
Cuevas Gonzalez JC, Gaitan Cepeda LA, Borges Yanez SA, Cornejo AD, Mori Estevez AD, Huerta ER (2016) p53 and p16 in oral epithelial dysplasia and oral squamous cell carcinoma: a study of 208 cases. Indian J Pathol Microbiol 59(2):153–158PubMedCrossRef
42.
Swaminathan U, Joshua E, Rao UK, Ranganathan K (2012) Expression of p53 and cyclin D1 in oral squamous cell carcinoma and normal mucosa: an immunohistochemical study. J Oral Maxillofac Pathol 16:172–177PubMedPubMedCentralCrossRef
43.
Hashmi AA, Hussain ZF, Hashmi SK, Irfan M, Khan EY, Faridi N et al (2018) Immunohistochemical over expression of p53 in head and neck squamous cell carcinoma: clinical and prognostic significance. BMC Res Notes 11:433PubMedPubMedCentralCrossRef
44.
Kannan S, Chandran GJ, Pillai KR, Mathew B, Sujathan K, Nalinakumary KR et al (1996) Expression of p53 in leukoplakia and squamous cell carcinoma of the oral mucosa: correlation with expression of Ki67. Clin Mol Pathol 49:170–175CrossRef
45.
Kerdpon D, Rich AM, Reade PC (1997) Expression of p53 in oral mucosal hyperplasia, dysplasia and squamous cell carcinoma. Oral Dis 3:86–92PubMedCrossRef
46.
Shiraki M, Odajima T, Ikeda T, Sasaki A, Satoh M, Yamaguchi A et al (2005) Combined expression of p53, cyclin D1 and epidermal growth factor receptor improves estimation of prognosis in curatively resected oral cancer. Mod Pathol 18:1482–1489PubMedCrossRef
47.
Siegelmann-Danieli N, Ben-Izhack O, Hanlon A, Ridge JA, Stein ME, Khandelwal V et al (2005) P53 alteration in oral tongue cancer is not significantly associated with age at diagnosis or tobacco exposure. Tumori 91:346–350PubMedCrossRef
48.
Abbas NF, El-Sharkawy SL, Abbas EA, El-Shaer MA (2007) Immunohistochemical study of p53 and angiogenesis in benign and preneoplastic oral lesions and oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103:385–390PubMedCrossRef
49.
Jain A, Maheshwari V, Mehdi G, Alam K, Sharma SC (2008) Diagnostic and prognostic significance of p53 protein expression in squamous cell lesions of the oral cavity. Int J Otorhinolaryngol 7:45–49
50.
De Oliveira LR, Ribeiro-Silva A, Zucoloto S (2007) Prognostic impact of p53 and p63 immunoexpression in oral squamous cell carcinoma. J Oral Pathol Med 36(4):191–197PubMedCrossRef
51.
Nie MH, Zhong L, Zeng GM, Li BQ (2002) The changes of cytokeratin 19 during oral carcinogenesis. Chin J Stomatol 37:187–191
52.
Hamakawa H, Bao Y, Takarada M, Fukuzumi M, Tanioka H (1998) Cytokeratin expression in squamous cell carcinoma of the lung and oral cavity: an immunohistochemical study with possible clinical relevance. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:438–443PubMedCrossRef
53.
Babiker AY, Rahmani AH, Abdalaziz MS, Albutti A, Aly SM, Ahmed HG (2014) Expressional analysis of p16 and cytokeratin19 protein in the genesis of oral squamous cell carcinoma patients. Int J Clin Exp Med 7:1524–1530PubMedPubMedCentral
54.
Vora HH, Shah NG, Patel DD, Trivedi TI, Chikhlikar PR (2003) Prognostic significance of biomarkers in squamous cell carcinoma of the tongue: multivariate analysis. J Surg Oncol 82:34–50PubMedCrossRef
Metadata
Title
p53, Cytokeratin 19 Expression in Oral Squamous Cell Carcinoma and Correlation with Histopathologic Grading: An Immunohistochemical Study
Authors
Harpreet Kaur
Vinay Hazarey
Gitika Sharma
Suchitra Gosavi
Rana AGK Pal
Vandana Gupta
Publication date
26-07-2023
Publisher
Springer India
Published in
Indian Journal of Otolaryngology and Head & Neck Surgery / Issue 1/2024
Print ISSN: 2231-3796
Electronic ISSN: 0973-7707
DOI
https://doi.org/10.1007/s12070-023-04092-7

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