Immunohistochemical expression of Cyclin D1 and p53 in normal, hyperplastic and malignant endometrium in a rural tertiary care hospital of central India
Keywords:
Endometrium, Carcinoma, Cyclin D1, p53 GenesAbstract
BACKGROUND: Endometrial carcinoma (EC) is the most common gynecological malignancy worldwide. Type I EC is often preceded by atypical endometrial hyperplasia (EH), while type II EC results from a series of genetic alterations involving activation of proto-oncogene (cyclin D1) and inactivation of tumor suppressor genes (p53). The purpose of this study was to evaluate prognostic significance of cyclic D1 and p53 expression in cases of EC by immunohistochemistry (IHC).
METHODS: This laboratory-based observational study was conducted in the histopathology section of the Department of Pathology at a rural tertiary care hospital in Central India from 2017 to 2019. The study comprised 100 cases, of which 50 cases were of EC and 38 and 12 cases of EH and normal endometrium, respectively. Relevant clinical details, histopathological diagnosis, treatment, and follow-up were retrieved from the Hospital Information System (HIS) and pathology records. IHC evaluation of cyclin D1 and p53 was done in all cases. Statistical analysis was done by descriptive and inferential statistics using a chi-square test through SPSS software.
RESULTS: Cyclin D1 was significantly over-expressed in atypical EH and type I EC. Overall, the positivity of cyclin D1 in EC was 88%. The high expression of cyclin D1 was significantly associated with poorly-differentiated tumors (P = 0.023). Overexpression of p53 was strongly associated with type II histology and poorly-differentiated type I EC, the presence of lymphovascular invasion (LVI) (P = 0.059), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.0011).
CONCLUSION: Cyclin D1 expression increased from normal endometrium to hyperplasia and EC, thus suggesting its role in the pathogenesis of type I EC, while p53 overexpression was significantly higher in type II EC and poorly-differentiated EC. Therefore, cyclin D1 and p53 can be used as a marker for endometrial carcinogenesis and tumor cell proliferation.
References
American Cancer Society. Cancer facts and figures 2022 [Online]. American Cancer Society; 2022. Available from: URL: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf.
Liu L, Habeshian TS, Zhang J, Peeri NC, Du M, De Vivo I, et al. Differential trends in rising endometrial cancer incidence by age, race, and ethnicity. JNCI Cancer Spectr. 2023; 7(1): pkad001.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1): 7-33.
Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update. 2017; 23(2): 232-54.
Mahdy H, Casey MJ, Vadakekut ES, Crotzer D. Endometrial cancer [Online]. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2024. Available from: URL: https://www.ncbi.nlm.nih.gov/books/NBK525981/.
Thukral S, Bhat S, Bashir N. Study of expression of PTEN and cyclin D1 in endometrium at a tertiary care centre. Int J Adv Med. 2019; 6(2): 495-501.
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.
Fadare O, Parkash V. P53 aberrations in low grade endometrioid carcinoma of the endometrium with nodal metastases: possible insights on pathogenesis discerned from immunohistochemistry. Diagn Pathol. 2017; 12(1): 81.
Ruhul Quddus M, Latkovich P, Castellani WJ, James Sung C, 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(4): 459-63.
Ozuysal S, Oztürk 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(2): 123-6.
Sindhu A, Kaur S, Kundu PR, Agarwal R, Singh Y, Mahajan P. Evaluation of expression of cyclin D1 in endometrial hyperplasia and endometrial carcinoma. Eur J Pharm Med Res. 2019; 6(1): 344-53.
Beavis AL, Najjar O, Cheskin LJ, Mangal R, Rositch AF, Langham G, et al. Prevalence of endometrial cancer symptoms among overweight and obese women presenting to a multidisciplinary weight management center. Gynecol Oncol Rep. 2020; 34: 100643.
Sangwan K, Garg M, Pathak N, Bharti L. Expression of cyclin D1 in Hyperplasia and carcinoma of endometrium and its correlation with histologic grade, tumor type, and clinicopathological features. J Lab Physicians. 2020; 12(3): 165-70.
Yildirim HT, Nergiz D, Sadullahoglu C, Akgunduz Z, Yildirim S, Dogan S, et al. The extent of cyclin D1 expression in endometrial pathologies and relevance of cyclin D1 with the clinicopathological features of endometrioid endometrial carcinoma. Indian J Pathol Microbiol. 2020; 63(3): 412-7.
Abdou AG, Al-Sharaky DR, Kasem HA, Abd El-Wahed MM. Clinicopathological differences between type I and type II endometrial carcinoma. Menoufia Med J. 2017; 30(3): 946-51.
Kundu PR, Sindhu A, Kaur S, Kulhria A, Hooda R. Expression of cyclin D1 in normal and hyperplastic endometrium. Int J Reprod Contracept Obstet Gynecol. 2019; 8(11): 4474-8.
Khabaz MN, Abdelrahman AS, Butt NS, Al-Maghrabi B, Al-Maghrabi J. Cyclin D1 is significantly associated with stage of tumor and predicts poor survival in endometrial carcinoma patients. Ann Diagn Pathol. 2017; 30: 47-51.
Shih H-C, 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(5): 471-8.
Kala M, Gill M, Gupta V, Srivastava D, Tanwar P, Goyal V. Cyclin D1 expression in hyperplasia and carcinoma of the endometrium and its correlation with histologic grade and tumor type. J Gynecol Surg. 2014; 30(1): 1-4.
Stavropoulos A, Varras M, Vasilakaki T, Varra VK, Tsavari A, Varra FN, et al. Expression of p53 and PTEN in human primary endometrial carcinomas: Clinicopathological and immunohistochemical analysis and study of their concomitant expression. Oncol Lett. 2019; 17(5): 4575-89.
Ray S, Jha A, Islam AA, Sengupta M. Study of prognostic and diagnostic significance of P53 and PTEN mutation in proliferative lesions of endometrium. J Curr Med Res Opin. 2020; 3(08): 563-9.
Ahmed NY, Isaac RH. P53 expression in endometrial hyperplasia and endometrial carcinoma. Zanco J Med Sci. 2010; 14(2): 28_34.
Sahin N, Bezmi, Akatli A, Akpolat N, Yilmaz E, Inci Coskun E, et al. The significance of p53 and estrogen expression in endometrial hyperplasias and endometrioid carcinomas: How should we evaluate immunohistochemistry? Clin Oncol Res. 2018; 1(1): 2-4.
Sherman ME, Bur ME, Kurman RJ. P53 in endometrial cancer and its putative precursors: evidence for diverse pathways of tumorigenesis. Hum Pathol. 1995; 26(11): 1268-74.
Akiyama A, Minaguchi T, Fujieda K, Hosokawa Y, Nishida K, Shikama A, et al. Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma. Oncol Lett. 2019; 18(6): 5952-8.
Hutt S, Tailor A, Ellis P, Michael A, Butler-Manuel S, Chatterjee J. The role of biomarkers in endometrial cancer and hyperplasia: a literature review. Acta Oncol. 2019; 58(3): 342-52.
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