Citation Information :
Bussari S, Ganvir SM, Sarode M, Jeergal PA, Deshmukh A, Srivastava H. Immunohistochemical Detection of Proliferative Marker Ki-67 in Benign and Malignant Salivary Gland Tumors. J Contemp Dent Pract 2018; 19 (4):375-383.
Introduction: Salivary gland tumors are the most histologically heterogeneous group of tumors with the greatest diversity of morphologic features among their cells and tissues. The present study was aimed at assessing the validity of Ki-67, a cell proliferation marker, as a prognostic factor in benign and malignant salivary gland tumors and to study whether it is related to age, sex, anatomical site, and size of the lesion in salivary gland tumors.
Materials and methods: A retrospective study consisted of benign salivary gland tumors (BSGTs) (n = 15), malignant salivary gland tumors (n = 18), and normal salivary gland parenchyma (n = 15).
Results: There was a significant difference of Ki-67 labeling index (LI, %) in normal salivary gland parenchyma, BSGTs, and malignant salivary gland tumors. The Ki-67 LI (%) in normal salivary gland parenchyma is negligible (0.27 ± 0.31%), whereas malignant salivary gland tumors showed very high Ki-67 LI (%) of 18.79 ± 18.06% compared with BSGTs being 0.76 ± 2.02%. There was a significant correlation statistically of mean ± standard deviation (SD) of Ki-67 LI (%) with the age of the patients being the maximum (32.68 ± 15.87%) in the 50 to 59 years age group, whereas sex, site of the lesion, and size of the lesion in salivary gland tumors had no significant correlation.
Conclusion: The Ki-67 is a useful marker for assessing proliferative potential of tumors.
Clinical significance: The Ki-67 LI% can be used as a reliable adjuvant diagnostic tool to differentiate between the subtypes and grading of certain malignant tumors, such as mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), and acinic cell carcinoma (AcCC), which are usually difficult to diagnose on histopathological criteria alone.
Neville, BW.; Damm, DD.; Allen, CM.; Bouquot, JE. Oral and maxillofacial pathology. 2nd ed. Philadelphia (PA): W.B. Saunders Company; 2004. pp. 406-430.
Skálová A, Leivo I. Cell proliferation in salivary gland tumors. Gen Diagn Pathol 1996 Jun;142(1):7-16.
Jordan RC, Daniels TE, Greenspan JS, Regezi JA. Advanced diagnostic methods in oral and maxillofacial pathology. Part II: immunohistochemical and immunofluorescent methods. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 Jan;93(1):56-74.
du Manoir S, Guillaud P, Camus E, Seigneurin D, Brugal G. Ki-67 labeling in postmitotic cells defines different ki-67 pathways within the 2c compartment. Cytometry 1991;12(5): 455-463.
Bhaskar, SN. Salivary glands. In: Orban's oral histology and embryology. 10th ed. New Delhi: CBS Publishers; 1990. pp. 328-361.
Hirabayashi S. Immunohistochemical detection of DNA topoisomerase Type II alpha and ki-67 in adenoid cystic carcinoma and pleomorphic adenoma of the salivary gland. J Oral Pathol Med 1999 Mar;28(3):131-136.
Okabe M, Inagaki H, Murase T, Inoue M, Nagai N, Eimoto T. Prognostic significance of p27 and ki-67 expression in mucoepidermoid carcinoma of the intraoral minor salivary gland. Mod Pathol 2001 Oct;14(10):1008-1014.
Skalova A, Lehtonen H, von Boguslawsky K, Leivo I. Prognostic significance of cell proliferation in mucoepidermoid carcinomas of the salivary gland: clinicopathological study using MIB 1 antibody in paraffin sections. Hum Pathol 1994 Sep;25(9):929-935.
Nordgård S, Franzén G, Boysen M, Halvorsen TB. Ki-67 as a prognostic marker in adenoid cystic carcinoma assessed with the monoclonal antibody MIB1 in paraffin sections. Laryngoscope 1997 Apr;107(4):531-536.
Hicks J, Flaitz C. Mucoepidermoid carcinoma of salivary glands in children and adolescents: assessment of proliferation markers. Oral Oncol 2000 Sep;36(5):454-460.
Mason DY, Gatter KC. The role of immunocytochemistry in diagnostic pathology. J Clin Pathol 1987 Sep;40(9):1042-1054.
Zhu Q, Tipoe GL, White FH. Proliferative activity as detected by immunostaining with ki-67 and proliferating cell nuclear antigen in benign and malignant epithelial lesions of the human parotid gland. Anal Quant Cytol Histol 1999 Aug;21(4): 336-342.
Kill IR. Localisation of the ki-67 antigen within the nucleolus. Evidence for a fibrillarin-deficient region of the dense fibrillar component. J Cell Sci 1996 Jun;109(Pt 6):1253-1263.
Scragg MA, Johnson NW. Epithelial cell kinetics–a review of methods of study and their application to oral mucosa in health and disease. Part A. Methods for studying cell proliferation and some sources of variation. J Oral Pathol 1980 Nov;9(6):309-341.
Jia-Xuan QI, Sheng-Rong ZH, Sudhott H, Hildman H. Expression of Ki-67, PCNA in parotid tumors. J US China Med Sci 2008;5:37-42.
Murakami M, Othani I, Hojo H, Wakasa H. Immunohistochemical evaluation with Ki-67: an application to salivary gland tumours. J Laryngol Otol 1992 Jan;106(1):35-38.
Alves FA, Perez DE, Almeida OP, Lopes MA, Kowalski LP. Pleomorphic adenoma of the submandibular gland: clinicopathological and immunohistochemical features of 60 cases in Brazil. Arch Otolaryngol Head Neck Surg 2002 Dec;128(12):1400-1403.
Alves FA, Pires FR, De Almeida OP, Lopes MA, Kowalski LP. PCNA, ki-67 and p53 expressions in submandibular salivary gland tumours. Int J Oral Maxillofac Surg 2004 Sep;33(6): 593-597.
Vargas PA, Cheng Y, Barrett AW, Craig GT, Speight PM. Expression of mcm-2, ki-67 and geminin in benign and malignant salivary gland tumours. J Oral Pathol Med 2008 May;37(5):309-318.
Nagao T, Sugano I, Ishida Y, Tajima Y, Matsuzaki O, Konno A, Kondo Y, Nagao K. Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases. Cancer 1998 Oct;83(7):1292-1299.
Ferri E, Pavon I, Armato E, Cavaleri S, Capuzzo P, Ianniello F. Myoepithelioma of a minor salivary gland of the cheek: case report. Acta Otorhinolaryngol Ital 2006 Feb;26(1):43-46.
Nguyen LH, Black MJ, Hier M, Chauvin P, Rochon L. HER2/ neu and Ki-67 as prognostic indicators in mucoepidermoid carcinomid carcinoma of salivary glands. J Otolaryngol 2003 Oct;32(5):328-331.
Triantafillidou K, Dimitrakopoulos J, Iordanidis F, Koufogiannis D. Mucoepidermoid carcinoma of minor salivary glands: a clinical study of 16 cases and review of the literature. Oral Dis 2006 Jul;12(4):364-370.
Amoueian S, Saghafi S, Farhadi F, Tohidi E, Sadegi L. Immunohistochemical assessment of Ki-67 expression in adenoid cystic carcinoma of the salivary glands. Iranian J Basic Med Sci 2007 Apr;10(2):84-89.
Simpson RH, Pereira EM, Ribeiro AC, Abdulkadir A, Reis- Filho JS. Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma. Histopathology 2002 Sep;41(3):250-259.
Darling MR, Schneider JW, Muller CJ. Differential immunohistochemical staining in polymorphous low grade adenocarcinoma and adenoid cystic carcinoma: Bcl-2, MIB-1 and TP53. Oral Biosci Med 2004 Jul;1(3):207-211.
Beltran D, Faquin WC, Gallagber G, August M. Selective immunohistochemical comparison of polymorphous lowgrade adenocarcinoma and adenoid cystic carcinoma. J Oral Maxillofac Surg 2006 Mar;64(3):415-423.
Lim JJ, Kang S, Lee MR, Pai HK, Yoon HJ, Lee JI, Hong SP, Lim CY. Expression of vascular endothelial growth factor in salivary gland carcinomas and its relation to p53, ki-67 and prognosis. J Oral Pathol Med 2003 Oct;32(9):552-561.