Study of expression of PTEN and Cyclin D1 in endometrium at a tertiary care centre
DOI:
https://doi.org/10.18203/2349-3933.ijam20191165Keywords:
Cyclin D1, Endometrial carcinoma, Hyperplastic, Neoplastic, Normal, PTENAbstract
Background: To study the expression of PTEN (Phosphatase and Tensin homologue) and Cyclin D1 in normal, hyperplastic and neoplastic endometrium by immunohistochemistry and to corroborate the interrelationship between PTEN and Cyclin D1 in normal to neoplastic endometrial disorders including endometrial carcinoma.
Methods: Formalin fixed paraffin embedded (FFPE) sections of spectrum of endometrium in fifty different cases were taken from secretory phase to endometrial carcinoma and subjected to Immunohistochemistry using PTEN and Cyclin D1 .
Results: Immunoreactivity was regarded as positive when brown staining was localized in the nuclei or cytoplasm. The intensity of nuclear staining was graded from 0 to 3+ and the extent was semi quantitatively estimated. If less than 10% of cells were positive a score of 0 was given, 11 % to 30% cell positivity was scored as 1+, 31% to 60 % positivity was scored as 2+ and more than 60% positive cells was labelled as 3+. Statistical analysis was performed with Chi-Square test and significant differences were noted between these 3 groups (p value < 0.05).
Conclusions: The present study supports that an inverse correlation exists in the expression of PTEN and Cyclin D1 in normal, hyperplastic and neoplastic endometrium. The decreased PTEN expression is a marker of the earliest endometrial premalignant lesions, and we propose that use of PTEN immunostaining may be informative in identifying premalignant lesions that are likely to progress to carcinoma. Cyclin D1 expression in endometrial glands increases progressively in intensity and extent from normal endometrium to hyperplasia to carcinoma.References
Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics.CA Cancer J Clin. 1998; 48:6-29.
Ellenson L H, Pirog EC. The Female Genital Tract. In: Kumar V, Abbas AK, Aster JC, editors. Robbins and Cotran Pathological Basis of Disease. 9th ed. Philadelphia: Saunders; 2015:1013.
Ronnett BM, Zaino RJ, Ellenson LH, Kurman RJ. Endometrial carcinoma. In: Kurman RJ, editor. Blaustein’s pathology of the female genital tract. 5th ed. Baltimore: Springer; 2002:501-559.
Wang Y, Zhu JF, Liu YY, Han GP. An analysis of Cyclin D1 , cytokeratin 5/6 and cytokeratin 8/18 expression in breast papillomas and papillary carcinomas. Diagn Pathol. 2013;8:8.
His ED, Zukerberg LR, Yang WI, Arnold A. Cyclin D1 /PRAD1 expression in parathyroid adenomas: an immunohistochemical study. J Clin Endocrinol Metab. 1996;81:1736.
Nishimura Y, Watanabe J, Jobo T, Kato N, Fujisawa T, Kamata Y, et al. Cyclin D1 expression in endometrioid-type endometrial adenocarcinoma is correlated with histological grade and proliferative activity, but not with prognosis. Anticancer Res. 2004;24:2185-91.
Wu W, Slomovitz BM, Soliman PT, Schmeler KM, Celestino J, Milam MR, et al. Correlation of Cyclin D1 and cyclin D3 overexpression with the loss of PTEN expression in endometrial carcinoma. Int J Gynecol Cancer. 2006;16:1668-72.
Nikaido T, Li SF, Shiozawa T, Fujii S. Coabnormal expression of Cyclin D1 and p53 protein in human uterine endometrial carcinomas. Cancer. 1996;78:1248-53.
Shih HC, Shiozawa T, Kato K, Imai T, Miyamoto T, Uchikawa J, et al. Immunohistochemical expression of cyclins, cyclin-dependent kinases, tumor-suppressor gene products, Ki-67, and sex steroid receptors in endometrial carcinoma: positive staining for cyclin A as a poor prognostic indicator. Hum Pathol. 2003;34:471-8.
Kanamori Y, Kigawa J, Itamochi H, Shimada M, Takahashi M, Kamazawa S, et al. Correlation between Loss of PTEN Expression and Akt Phosphorylation in Endometrial Carcinoma. Clin Cancer Res. 2001;7(4):892-95.
Mutter GL. PTEN, a protean tumor suppressor. Am J Pathol. 2001;158:1895-98.
Djordjevic B, Hennessy BT, Li J, Barkoh BA, Luthra R, Mills GB, et al. Clinical assessment of PTEN loss in endometrial carcinoma: immunohistochemistry out-performs gene sequencing. Mod Pathol. 2012.25(5):699-708.
Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JPA, Lees JA, et al. Altered PTEN Expression as a Diagnostic Marker for the Earliest Endometrial Precancers. J Natl Cancer Inst. 2000;92(11):924-30.
Horrée N, van Diest PJ, van der Groep P, Sie-Go DM, Heintz AP. Progressive derailment of cell cycle regulators in endometrial carcinogenesis. J Clin Pathol. 2008;61:36-42.
Quddus MR, Latkovich P, Castellani WJ, Sung CJ, Steinhoff MM, Briggs RC, et al. Expression of Cyclin D1 in normal, metaplastic, hyperplastic endometrium and endometrioid carcinoma suggests a role in endometrial carcinogenesis. Arch Pathol Lab Med. 2002;126:459-63.
Chaudhary M, Bansal S. Expression of Cyclin D1 in endometrial hyperplasia and carcinoma. Ind J Pathol Microbiol. 2007;50:708-10.
Ashton KA, Proietto A, Otton G, Symonds I, McEvoy M, Attia J, et al. The influence of the Cyclin D1 870 G>A polymorphism as an endometrial cancer risk factor. BMC Cancer. 2008;8:272.
Abdel-Aziz AF, El-Refaeey AA, Elsaeid AM, Refaat M. Cyclin D1 G870A Polymorphism is associated with an increased risk of simple endometrial hyperplasia in Egyptian women. Biochem Physiol. 2014;3:123.
Erkanli S, Kayaselcuk F, Kuscu E, Bagis T, Bolat F, Haberal A, et al. Expression of survivin, PTEN and p27 in normal, hyperplastic, and carcinomatous endometrium. Int J Gynecol Cancer. 2006;16:1412-18.
Rao AC, Arya G, Padma PJ. Immunohistochemical phospho tensin tumor suppressor gene staining patterns in endometrial hyperplasias: a 2-year study. Indian J Pathol Microbiol. 2011;54(2):264-8.
Sarmadi S, Mood NI, Sotoudeh, Tavangar S M. Altered PTEN expression; a diagnostic marker for differentiating normal, hyperplastic and neoplastic endometrium. Diagn Pathol. 2009;4:41.
Lee H, Choi HJ, Kang CS, Lee HJ, Lee WS, Park CS. Expression of miRNAs and PTEN in endometrial specimens ranging from histologically normal to hyperplasia and endometrial adenocarcinoma. Modern Pathol. 2012; 25:1508-15.
Sheikh S A, Elyasergy DF. Immunoreactivity of PTEN in Cyclic Endometrium and Endometrial Hyperplasia. World J Med Sci. 2016;13(2):126-32.
Tantbirojn P, Triratanachat S, Trivijitsilp P, Niruthisard S. Detection of PTEN immunoreactivity in endometrial hyperplasia and adenocarcinoma. J Med Assoc Thai. 2008;91(8):1161-5.
Orbo A, Nilsen MN, Arnes MS, Pettersen I, Larsen K. Loss of expression of MLH1, MSH2, MSH6, and PTEN related to endometrial cancer in 68 patients with endometrial hyperplasia. Int J Gynecol Pathol. 2003;22(2):141-8.
Terakawa N, Kanamori Y, Yoshida S. Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer. Endo Rel Cancer. 2003;10(2):203-8.
Bueno GM, Perales SR, Estevez CS, Marcos R, Hardisson D, Cigudosa JC, et al. Molecular alterations associated with Cyclin D1 overexpression in endometrial cancer. Int J Cancer. 2003;110:194-200.
Ozuysal S, Ozturk H, Bilgin T, Filiz G. Expression of Cyclin D1 in normal, hyperplastic and neoplastic endometrium and its correlation with Ki-67 and clinicopathological variables. Arch Gynecol Obstet. 2005;271:123-6.
Tsuda H, Yamamoto K, Inoue T, Uchiyama I, Umesaki N. The role of p16-cyclin D/CDK-pRb pathway in the tumourigenesis of endometrioid-type endometrial carcinoma. Br J Cancer. 2000;82:675-82.
Cao QJ, Einstein MH, Anderson PS, Runowicz CD, Balan R, Jones JG. Expression of COX 2, Ki-67, Cyclin D1 and p21 in endometrioid endometrial carcinoma. Int J Gynecol Pathol. 2002;21:147-54.
Liang S, Mu K, Wang Y, Zhou Z, Zhang J, Sheng Y, et al. Cyclin D1, a prominent prognostic marker for endometrial diseases. Diagn Pathol. 2013;8:138.
