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Published in: Head and Neck Pathology 4/2010

01-12-2010 | Original Paper

Analysis of Immunohistochemical Expression of K19 in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma Using Color Deconvolution-Image Analysis Method

Authors: Rima A. Safadi, Atika S. Musleh, Taiseer H. Al-Khateeb, Abed Al-Hadi Hamasha

Published in: Head and Neck Pathology | Issue 4/2010

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Abstract

K19 is an intermediate filament protein that has been investigated in oral squamous cell carcinoma (OSCC), but that has not been correlated with the amount of keratin produced within well-differentiated OSCC grade. The aim of the present study was to objectively analyze K19 immunoexpression in OSCC and to validate the utility of K19 in differentiation among grades of oral epithelial dysplasia (OED). Formalin-fixed tissues of 36 primary OSCC (22 well, 10 moderately, 4 poorly differentiated), 43 OED (23 mild, 8 moderate, 12 severe), and 11 normal oral epithelium (NOE) were included. K19 was immunostained using HRP-DAB method. The percentage of K19-positive area was found using color deconvolution program in ImageJ® image analysis system (public domain software, National Institutes of Health, Bethesda, MD, USA) and analyzed using independent samples t tests and ANOVA test. K19 scores in NOE, mild, moderate and severe OED were: 1.8, 3.4, 21, and 50.3%, respectively, with significant association with the grade (t test P < 0.05). Well-differentiated OSCC with <30% keratin pearl formation expressed significantly higher K19 scores compared to well-differentiated OSCC with >30% keratin pearls (28.6 and 1.2%, respectively, P < 0.05). K19 scores in moderately and poorly differentiated OSCC were 60.8 and 61.3%, respectively. K19 scores significantly differentiated between two subgroups of tumors within well-differentiated OSCC grade and reflected histologic differentiation as well as probably predicting the clinical outcome. Combining K19 immunostain with the regular H&E stain may be helpful to facilitate and assure assigning a more accurate grade for OED.
Literature
1.
go back to reference De Vicente J, Recio O, Pendás S, et al. Oral squamous cell carcinoma of the mandibular region A survival study. Head Neck. 2001;23(7):536–43.CrossRefPubMed De Vicente J, Recio O, Pendás S, et al. Oral squamous cell carcinoma of the mandibular region A survival study. Head Neck. 2001;23(7):536–43.CrossRefPubMed
2.
go back to reference Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4–5):309–16.CrossRefPubMed Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4–5):309–16.CrossRefPubMed
3.
go back to reference Silverman SJ, Sugerman P. Oral premalignancies and squamous cell carcinoma. Clin Dermatol. 2000;18(5):563–8.CrossRefPubMed Silverman SJ, Sugerman P. Oral premalignancies and squamous cell carcinoma. Clin Dermatol. 2000;18(5):563–8.CrossRefPubMed
4.
go back to reference Kramer I, Lucas R, Pindborg J, et al. Definition of leukoplakia and related lesions: An aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol. 1978;46(4):518–39.CrossRefPubMed Kramer I, Lucas R, Pindborg J, et al. Definition of leukoplakia and related lesions: An aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol. 1978;46(4):518–39.CrossRefPubMed
5.
go back to reference Silverman SJ, Gorsky M, Kaugars G. Leukoplakia, dysplasia, and malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82(2):117.CrossRefPubMed Silverman SJ, Gorsky M, Kaugars G. Leukoplakia, dysplasia, and malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82(2):117.CrossRefPubMed
6.
go back to reference Abbey L, Kaugars G, Gunsolley J, et al. Intraexaminer and interexaminer reliability in the diagnosis of oral epithelial dysplasia. Oral Pathol Oral Radiol Endod. 1995;80(2):188–91.CrossRef Abbey L, Kaugars G, Gunsolley J, et al. Intraexaminer and interexaminer reliability in the diagnosis of oral epithelial dysplasia. Oral Pathol Oral Radiol Endod. 1995;80(2):188–91.CrossRef
7.
go back to reference Brothwell DJ, Lewis DW, Bradley G, et al. Observer agreement in the grading of oral epithelial dysplasia. Community Dent Oral Epidemiol. 2003;31(4):300–5.CrossRefPubMed Brothwell DJ, Lewis DW, Bradley G, et al. Observer agreement in the grading of oral epithelial dysplasia. Community Dent Oral Epidemiol. 2003;31(4):300–5.CrossRefPubMed
8.
go back to reference Fischer DJ, Epstein JB, Morton TH, et al. Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions. J Oral Pathol Med. 2004;33(2):65–70.CrossRefPubMed Fischer DJ, Epstein JB, Morton TH, et al. Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions. J Oral Pathol Med. 2004;33(2):65–70.CrossRefPubMed
9.
go back to reference Hu L, Crowe DL, Rheinwald JG, et al. Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines. Cancer Res. 1991;51(15):3972–81.PubMed Hu L, Crowe DL, Rheinwald JG, et al. Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines. Cancer Res. 1991;51(15):3972–81.PubMed
10.
go back to reference Takeda T, Sugihara K, Hirayama Y, et al. Immunohistological evaluation of Ki-67, p63, CK19 and p53 expression in oral epithelial dysplasias. J Oral Pathol Med. 2006;35(6):369–75.CrossRefPubMed Takeda T, Sugihara K, Hirayama Y, et al. Immunohistological evaluation of Ki-67, p63, CK19 and p53 expression in oral epithelial dysplasias. J Oral Pathol Med. 2006;35(6):369–75.CrossRefPubMed
11.
go back to reference Warnakulasuriya S. Lack of molecular markers to predict malignant potential of oral precancer. J Pathol. 2000;190(4):407–9.CrossRefPubMed Warnakulasuriya S. Lack of molecular markers to predict malignant potential of oral precancer. J Pathol. 2000;190(4):407–9.CrossRefPubMed
12.
go back to reference Fradette J, Germain L, Seshaiah P, et al. The type I keratin 19 possesses distinct and context-dependent assembly properties. J Biol Chem. 1998;273(52):35176–84.CrossRefPubMed Fradette J, Germain L, Seshaiah P, et al. The type I keratin 19 possesses distinct and context-dependent assembly properties. J Biol Chem. 1998;273(52):35176–84.CrossRefPubMed
13.
go back to reference Michel M, Torok N, Godbout MJ, et al. Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: Keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage. J Cell Sci. 1996;109(Pt5):1017–70.PubMed Michel M, Torok N, Godbout MJ, et al. Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: Keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage. J Cell Sci. 1996;109(Pt5):1017–70.PubMed
14.
go back to reference Lindberg K, Rheinwald JG. Suprabasal 40kd keratin (K19) expression as an immunohistologic marker of premalignancy in oral epithelium. Am J Pathol. 1989;134(1):89–98.PubMed Lindberg K, Rheinwald JG. Suprabasal 40kd keratin (K19) expression as an immunohistologic marker of premalignancy in oral epithelium. Am J Pathol. 1989;134(1):89–98.PubMed
15.
go back to reference Zhong LP, Chen WT, Zhang CP, et al. Increased CK19 expression correlated with pathologic differentiation grade and prognosis in oral squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104(3):377–84.CrossRefPubMed Zhong LP, Chen WT, Zhang CP, et al. Increased CK19 expression correlated with pathologic differentiation grade and prognosis in oral squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104(3):377–84.CrossRefPubMed
16.
go back to reference Anneroth G, Hansen LS. A methodologic study of histologic classification and grading of malignancy in oral squamous cell carcinoma. Scand J Dent Res. 1984;92(5):448–68.PubMed Anneroth G, Hansen LS. A methodologic study of histologic classification and grading of malignancy in oral squamous cell carcinoma. Scand J Dent Res. 1984;92(5):448–68.PubMed
17.
go back to reference Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol. 2001;23(4):291–9.PubMed Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol. 2001;23(4):291–9.PubMed
18.
go back to reference Elias JM, Gown AM, Nakamura RM, et al. Quality control in immunohistochemistry. Report of a workshop sponsored by the Biological Stain Commission. Am J Clin Pathol. 1989;92(6):836–43.PubMed Elias JM, Gown AM, Nakamura RM, et al. Quality control in immunohistochemistry. Report of a workshop sponsored by the Biological Stain Commission. Am J Clin Pathol. 1989;92(6):836–43.PubMed
19.
go back to reference Fillies T, Jogschies M, Kleinheinz J, et al. Cytokeratin alteration in oral leukoplakia and oral squamous cell carcinoma. Oncol Rep. 2007;18(3):639–43.PubMed Fillies T, Jogschies M, Kleinheinz J, et al. Cytokeratin alteration in oral leukoplakia and oral squamous cell carcinoma. Oncol Rep. 2007;18(3):639–43.PubMed
20.
go back to reference Nie M, Zhong L, Zeng G, et al. The changes of cytokeratin 19 during oral carcinogenesis. Zhonghua Kou Qiang Yi Xue Za Zhi. 2002;37(3):187–90.PubMed Nie M, Zhong L, Zeng G, et al. The changes of cytokeratin 19 during oral carcinogenesis. Zhonghua Kou Qiang Yi Xue Za Zhi. 2002;37(3):187–90.PubMed
21.
go back to reference Küffer R, Lombardi T. Premalignant lesions of the oral mucosa. A discussion about the place of oral intraepithelial neoplasia (OIN). Oral Oncol. 2002;38(2):125–30.CrossRefPubMed Küffer R, Lombardi T. Premalignant lesions of the oral mucosa. A discussion about the place of oral intraepithelial neoplasia (OIN). Oral Oncol. 2002;38(2):125–30.CrossRefPubMed
22.
go back to reference Warnakulasuriya S, Reibel J, Bouquot J, et al. Oral epithelial dysplasia classification systems: Predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008;37(3):127–33.CrossRefPubMed Warnakulasuriya S, Reibel J, Bouquot J, et al. Oral epithelial dysplasia classification systems: Predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008;37(3):127–33.CrossRefPubMed
23.
go back to reference Kujan O, Oliver RJ, Khattab A, et al. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42(10):987–93.CrossRefPubMed Kujan O, Oliver RJ, Khattab A, et al. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42(10):987–93.CrossRefPubMed
24.
go back to reference Su L, Morgan PR, Thomas JA, et al. Expression of keratin 14 and 19 mRNA and protein in normal oral epithelia, hairy leukoplakia, tongue biting and white sponge nevus. J Oral Pathol Med. 1993;22(4):183–9.CrossRefPubMed Su L, Morgan PR, Thomas JA, et al. Expression of keratin 14 and 19 mRNA and protein in normal oral epithelia, hairy leukoplakia, tongue biting and white sponge nevus. J Oral Pathol Med. 1993;22(4):183–9.CrossRefPubMed
25.
go back to reference Toyoshima T, Vairaktaris E, Nkenke E, et al. Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma. J Cancer Res Clin Oncol Erratum in: J Cancer Res Clin Oncol. 2008;34(4):523-24,134(4):515-21. Toyoshima T, Vairaktaris E, Nkenke E, et al. Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma. J Cancer Res Clin Oncol Erratum in: J Cancer Res Clin Oncol. 2008;34(4):523-24,134(4):515-21.
26.
go back to reference Fillies T, Werkmeister R, Packeisen J, et al. Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity. BMC Cancer. 2006;13(6):10.CrossRef Fillies T, Werkmeister R, Packeisen J, et al. Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity. BMC Cancer. 2006;13(6):10.CrossRef
27.
go back to reference Yoshida Y. [Effective biological marker to detect oral squamous cancer cells–expression patterns of CK 10, 17, 19 and SCCA mRNA–]. Kokubyo, Gakkai Zasshi. 2007;73 74 (3,1):37-42. Yoshida Y. [Effective biological marker to detect oral squamous cancer cells–expression patterns of CK 10, 17, 19 and SCCA mRNA–]. Kokubyo, Gakkai Zasshi. 2007;73 74 (3,1):37-42.
28.
go back to reference Bryne M. Is the invasive front of an oral carcinoma the most important area for prognostication? Oral Dis. 1998;4(2):70–7.CrossRefPubMed Bryne M. Is the invasive front of an oral carcinoma the most important area for prognostication? Oral Dis. 1998;4(2):70–7.CrossRefPubMed
Metadata
Title
Analysis of Immunohistochemical Expression of K19 in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma Using Color Deconvolution-Image Analysis Method
Authors
Rima A. Safadi
Atika S. Musleh
Taiseer H. Al-Khateeb
Abed Al-Hadi Hamasha
Publication date
01-12-2010
Publisher
Springer US
Published in
Head and Neck Pathology / Issue 4/2010
Electronic ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-010-0210-6

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