Selçuk AYAS, Lütfiye UYGUR, Nermin KOÇ, Nurver ÖZEL ÖZBAY

Comparison of the distinctive pathological features of and p16 and c-Kit expression levels in benign and malignant endometrial polyps

Background/aim: Histopathological examination is crucial for the effective management of endometrial polyps. Immunohistochemical markers such as p16 and c-Kit may facilitate the differential diagnoses of benign and malignant polyps. The aim of the present study was to explore the expression levels of c-Kit (CD117) and p16 in endometrial polyps of postmenopausal women. Materials and methods: Twenty-five hysterectomy specimens with malignant endometrial polyps and hysterectomy or polypectomy specimens featuring 55 benign polyps were studied. The polyps were immunohistochemically stained for p16 and c-Kit, and differences in the expression levels of these proteins in the glandular and stromal components of benign polyps and the benign regions of the malignant polyps were assessed by using Fisher s exact test. Results: The glandular components of malignant polyps exhibited significantly more intense p16 immunostaining than did benign polyps. Most immunoreactive cells were glandular cells exhibiting tubal metaplasia. The stromal components of either type of polyp did not differ in terms of p16 immunostaining. The extent of c-Kit immunostaining in benign and malignant polyps was similar. Conclusion: The extensive tubal metaplasia in and the p16 immunoreactivity of the glandular components of malignant polyps may be useful to distinguish such polyps from benign polyps.

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1. Ishida M, Iwai M, Yoshida K, Kagotani A, Okabe H. Clear cell adenocarcinoma present exclusively within endometrial polyp: report of two cases. Int J Clin Exp Pathol 2014; 7: 1757-1763.
2. Ferrazzi E, Zupi E, Leone FP, Savelli L, Omodei U, Moscarini M, Barbieri M, Cammareri G, Capobianco G, Cicinelli E et al. How often are endometrial polyps malignant in asymptomatic postmenopausal women? A multicenter study. Am J Obstet Gynecol 2009; 200: 235.e1-6.
3. Lee SC, Kaunitz AM, Sanchez-Ramos L, Rhatigan RM. The oncogenic potential of endometrial polyps: a systematic review and meta-analysis. Obstet Gynecol 2010; 116: 1197-1205.
4. Perez-Medina T, Bajo J, Huertas MA, Rubio A. Predicting atypia inside endometrial polyps. J Ultrasound Med 2002; 21: 125-128.
5. Burnett JE Jr. Hysteroscopy-controlled curettage for endometrial polyps. Obstet Gynecol 1964; 24: 621-625.
6. Guido RS, Kanbour-Shakir A, Rulin MC, Christopherson WA. Pipelle endometrial sampling. Sensitivity in the detection of endometrial cancer. J Reprod Med 1995; 40: 553-555.
7. Savelli L, De Iaco P, Santini D, Rosati F, Ghi T, Pignotti E, Bovicelli L. Histopathologic features and risk factors for benignity, hyperplasia, and cancer in endometrial polyps. Am J Obstet Gynecol 2003; 188: 927-931.
8. Ben-Arie A, Goldchmit C, Laviv Y, Levy R, Caspi B, Huszar M, Dgani R, Hagay Z. The malignant potential of endometrial polyps. Eur J Obstet Gynecol Reprod Biol 2004; 115: 206-210.
9. Gregoriou O, Konidaris S, Vrachnis N, Bakalianou K, Salakos N, Papadias K, Kondi-Pafiti A, Creatsas G. Clinical parameters linked with malignancy in endometrial polyps. Climacteric 2009; 12: 454-458.
10. Antunes A Jr, Andrade LA, Pinto GA, Leão R, Pinto-Neto AM, Costa-Paiva L. Is the immunohistochemical expression of proliferation (Ki-67) and apoptosis (Bcl-2) markers and cyclooxigenase-2 (COX-2) related to carcinogenesis in postmenopausal endometrial polyps? Anal Quant Cytopathol Histpathol 2012; 34: 264-272.
11. Antunes A Jr, Vassallo J, Pinheiro A, Leão R, Neto AM, CostaPaiva L. Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps: a comparison between benign and malignant polyps in postmenopausal patients. Oncol Lett 2014; 7: 1944-1950.
12. Stewart CJ, Bharat C, Crook M. p16 immunoreactivity in endometrial stromal cells: stromal p16 expression characterises but is not specific for endometrial polyps. Pathology 2015; 47: 112-117.
13. Moritani S, Ichihara S, Hasegawa M, Iwakoshi A, Murakami S, Sato T, Okamoto T, Mori Y, Kuhara H, Silverberg SG. Stromal p16 expression differentiates endometrial polyp from endometrial hyperplasia. Virchows Arch 2012; 461: 141-148.
14. Buchynska LG, Nesina IP. Expression of the cell cycle regulators p53, p21 (WAF1/CIP1) and p16 (INK4a) in human endometrial adenocarcinoma. Exp Oncol 2006; 28: 152-155.
15. ONeill CJ, McCluggage WG. p16 expression in the female genital tract and its value in diagnosis. Adv Anat Pathol 2006; 13: 8-15.
16. Nielsen GP, Stemmer-Rachamimov AO, Ino Y, Moller MB, Rosenberg AE, Louis DN. Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation. Am J Pathol 1999; 155: 1879-1884.
17. Elmore LW, Domson K, Moore JR, Kornstein M, Burks RT. Expression of c-Kit (CD117) in benign and malignant human endometrial epithelium. Arch Pathol Lab Med 2001; 125: 146- 151.
18. Scobie JV, Acs G, Bandera CA, Blank SV, Wheeler JE, Pasha TL, Salscheider M, Zhang PJ. c-Kit immunoreactivity in endometrial adenocarcinomas and its clinicopathologic significance. Int J Gynecol Pathol 2003; 22: 149-155.
19. Klein WM, Kurman RJ. Lack of expression of c-Kit protein (CD117) in mesenchymal tumors of the uterus and ovary. Int J Gynecol Pathol 2003; 22: 181-184.
20. Miettinen M, Lasota J. KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 2005; 13: 205-220.
21. Hui P, Kelly M, OMalley DM, Tavassoli F, Schwartz PE. Minimal uterine serous carcinoma: a clinicopathological study of 40 cases. Mod Pathol 2005; 18: 75-82.
22. Shiozawa T, Nikaido T, Shimizu M, Zhai Y, Fujii S. Immunohistochemical analysis of the expression of cdk4 and p16INK4 in human endometrioid‐type endometrial carcinoma. Cancer 1997; 80: 2250-2256.
23. Lenci MA, Nascimento VA, Grandini AB. Premalignant and malignant lesions in endometrial polyps in patients undergoing hysteroscopic polypectomy. Einstein (São Paulo) 2014; 12: 16- 21.
24. Kurman RJ, Hedrick Ellenson L, Ronnett BM. Blausteins Pathology of the Female Genital Tract. 6th ed. New York, NY, USA: Springer-Verlag; 2011.
25. Martín-Ondarza C, Gil-Moreno A, Torres-Cuesta L, García A, Eyzaguirre F, Díaz-Feijoo B, Xercavins J. Endometrial cancer in polyps: a clinical study of 27 cases. Eur J Gynaecol Oncol 2004; 26: 55-58.
26. Lieng M, Istre O, Qvigstad E. Treatment of endometrial polyps: a systematic review. Acta Obstet Gynecol Scand 2010; 89: 992- 1002.
27. Martini M, Ciccarone M, Garganese G, Maggiore C, Evangelista A, Rahimi S, Zannoni G, Vittori G, Larocca LM. Possible involvement of hMLH1, p16INK4a and PTEN in the malignant transformation of endometriosis. Int J Cancer 2002; 102: 398-406.
28. Carlson JW, Mutter GL. Endometrial intraepithelial neoplasia is associated with polyps and frequently has metaplastic change. Histopathology 2008; 53: 325-332.
29. Andersen WA, Taylor PT Jr, Fechner RE, Pinkerton JA. Endometrial metaplasia associated with endometrial adenocarcmoma. Am J Obstet Gynecol 1987; 157: 597-604.
30. Horree N, Heintz AP, Sie-Go DM, van Diest PJ. p16 is consistently expressed in endometrial tubal metaplasia. Cell Oncol 2007; 29: 37-45.
31. Arber DA, Tamayo R, Weiss LM. Paraffin section detection of the c-Kit gene product (CD 117) in human tissues: value in the diagnosis of mast cell disorders. Hum Pathol 1998; 29: 498-504.