Iranian Journal of Pathology

Utility of ER, p53, CEA and Napsin A in Histological Subtyping of Endometrial Carcinoma and Their Correlation with Clinicopathological Prognostic Parameters: Experience from a Referral Institute

Document Type : Original Research

Authors

Saumya Shivakumar 1
Kausalya Kumari Sahu 2
Ranjitha Rao 2
Chaithra GV 2
Cheryl Sarah Philipose 2
Sharada Rai 2

1 All India Institute of Medical Sciences, Bhopal, India

2 Department of Pathology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India

https://doi.org/10.30699/ijp.2024.2008693.3154
Abstract
Background & Objective: Endometrial Carcinoma (EC) is the most common gynecological cancer with a global incidence of 23.2 per 1 lakh population. Histological subclassification of EC is extremely crucial for the diagnosis, proper management strategies, and prognosis. This study was conducted in a tertiary care institute to analyze the expression pattern of a minimum panel of 4 markers (ER, p53, CEA, Napsin A) with emphasis on their utility in the routine histological subtyping, aberrant expression, and correlation with various clinicopathological parameters.
Methods: A time-bound cross-sectional observational and analytical study was conducted, which includes cases diagnosed in our laboratory from January 2016 to April 2021.
Results: Sixty cases diagnosed as EC during the study period formed the sample cases. The ER was expressed in 85% (53/60) of cases in the current study. Among them, 94% (50/53) were endometrioid endometrial carcinomas (EECs). A negative correlation was found between ER intensity and age (r= -1.48). Of 60 EC cases, 10 (16%) cases expressed p53. The tumors positive for p53 with higher intensity were negative for ER and vice versa. The expression pattern of ER and p53 was statistically significant (P=-0.021). On IHC, 84.6% (11/13) of CEA-positive cases expressed both ER and CEA, suggesting mucinous differentiation. Napsin A was expressed in two cases of EEC, FIGO grade I, and one case of serous carcinoma.
Conclusion: An inverse association was found between ER and p53 expression. The CEA is valuable in identifying EEC with mucinous differentiation.

Keywords

Cancer
Carcinoma
CEA
Endometrial
ER
Napsin A
p53

Subjects

  1. Salama A, Arafa M, ElZahaf E, Shebl AM, Awad AA, Ashamallah SA, Hemida R, Gamal A, Zalata K, Abdel-Hady ES. Potential role for a panel of immunohistochemical markers in the management of endometrial carcinoma. J Pathol Transl Med. 2019;53(3):164-72. [DOI:10.4132/jptm.2019.02.12] [PMID]
  2. Zhao J, Hu Y, Zhao Y, Chen D, Fang T, Ding M. Risk factors of endometrial cancer in patients with endometrial hyperplasia: implication for clinical treatments. BMC Women's Health. 2021;21(1):1-6. [DOI:10.1186/s12905-021-01452-9] [PMID]
  3. Dawodu OO, Okunade KS, Daramola A, Banjo AA. Review of immunohistochemical typing of endometrial carcinoma at the Lagos University Teaching Hospital. Afr Health Sci. 2019;19(3):2468-75. [DOI:10.4314/ahs.v19i3.22] [PMID]
  4. Rana MK, Barwal TS, Sharma U, Bansal R, Singh K, Rana AP, Jain A, Khera U, Singh Sr K. Current Trends of Carcinoma: Experience of a Tertiary Care Cancer Center in North India. Cureus. 2021;13(6). [DOI:10.7759/cureus.15788]
  5. Prat J, Mutch DG. Pathology of cancers of the female genital tract including molecular pathology. Int J Gynecology & Obstetrics. 2018;143:93-108. [DOI:10.1002/ijgo.12617] [PMID]
  6. Heinzelmann-Schwarz V, Kind AB, Vetter M, Russell K, Omar S, Schoetzau A, Hoeck K, Fink D, Friedlander ML, Hacker NF. Should MMMT still be treated with adjuvant taxane-based combination chemotherapy?. J Cancer Res Clin Oncol. 2020;146:695-704. [DOI:10.1007/s00432-019-03091-y] [PMID]
  7. Ren S, Wu J, Yin W, Liao Q, Gong S, Xuan B, Mu X. Researches on the correlation between estrogen and progesterone receptors expression and disease-free survival of endometrial cancer. Cancer Manag Res. 2020:12635-47. [DOI:10.2147/CMAR.S263219] [PMID]
  8. Stavropoulos A, Varras M, Vasilakaki T, Varra VK, Tsavari A, Varra FN, Nonni A, Kavantzas N, Lazaris AC. 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. [DOI:10.3892/ol.2019.10093] [PMID]
  9. Yanaranop M, Ayuwat S, Nakrangsee S. Differential diagnosis between primary endocervical and endometrial adenocarcinoma using immunohistochemical staining of estrogen receptor, vi-mentin, carcinoembryonic antigen and p16. J Med Assoc Thai. 2016;99(Suppl 2):S106-15.
  10. Weidemann S, Böhle JL, Contreras H, Luebke AM, Kluth M, Büscheck F, et al. Napsin A Expression in Human Tumors and Normal Tissues. 2021;27:1-12. [DOI:10.3389/pore.2021.613099] [PMID]
  11. Weinberger V, Bednarikova M, Hausnerová J, Ovesná P, Vinklerová P, Minar L, Felsinger M, Jandáková E, Cihalova M, Zikán M. A novel approach to preoperative risk stratification in endometrial cancer: the added value of immunohistochemical markers. Front Oncol. 2019;9:265. [DOI:10.3389/fonc.2019.00265] [PMID]
  12. Wu C, Chen R, Xu L, Chen Y, Wang Y, Huang G, Liu J. Relationship between the expression of oestrogen receptor and progesterone receptor and 18F-FDG uptake in endometrial cancer. Aging (Albany NY). 2020;12(13):12921. [DOI:10.18632/aging.103352] [PMID]
  13. Shen F, Gao Y, Ding J, Chen Q. Is the positivity of estrogen receptor or progesterone receptor different between type 1 and type 2 endometrial cancer?. Oncotarget. 2017;8(1):506. [DOI:10.18632/oncotarget.13471] [PMID]
  14. Wang C, Tran DA, Fu MZ, Chen W, Fu SW, Li X. Estrogen receptor, progesterone receptor, and HER2 receptor markers in endometrial cancer. J Cancer. 2020;11(7):1693. [DOI:10.7150/jca.41943] [PMID]
  15. Watkins JC, Downing MJ, Crous-Bou M, Busch EL, Chen MM, De Vivo I, Mutter GL. Endometrial tumor classification by histomorphology and biomarkers in the Nurses’ Health Study. J Cancer Epidemiol. 2021;2021. [DOI:10.1155/2021/8884364] [PMID]
  16. Shivkumar VB, Atram MA, Gangane NM. Expression of ER/PR receptor, Her-2/neu, Ki67 and p53 in endometrial carcinoma: clinicopathological implication and prognostic value.  Indian J Gynecol Oncol. 2020;18:1-9. [DOI:10.1007/s40944-020-00436-1]
  17. Srijaipracharoen S, Tangjitgamol S, Tanvanich S, Manusirivithaya S, Khunnarong J, Thavaramara T, Leelahakorn S, Pataradool K. Expression of ER, PR, and Her-2/neu in endometrial cancer: a clinicopathological study. Asian Pac J Cancer Prev. 2010;11(1):215-20.
  18. Reid-Nicholson M, Iyengar P, Hummer AJ, Linkov I, Asher M, Soslow RA. Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis. Mod Pathol. 2006;19(8):1091-100. [DOI:10.1038/modpathol.3800620] [PMID]
  19. Jeon YT, Park IA, Kim YB, Kim JW, Park NH, Kang SB, Lee HP, Song YS. Steroid receptor expressions in endometrial cancer: clinical significance and epidemiological implication. Cancer Lett. 2006;239(2):198-204. [DOI:10.1016/j.canlet.2005.08.001] [PMID]
  20. Jongen V, Briët J, de Jong R, ten Hoor K, Boezen M, van der Zee A, Nijman H, Hollema H. Expression of estrogen receptor-alpha and-beta and progesterone receptor-A and-B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol. 2009;112(3):537-42. [DOI:10.1016/j.ygyno.2008.10.032] [PMID]
  21. Guan J, Xie L, Luo X, Yang B, Zhang H, Zhu Q, Chen X. The prognostic significance of estrogen and progesterone receptors in grade I and II endometrioid endometrial adenocarcinoma: hormone receptors in risk stratification. J Gynecol Oncol. 2019;30(1). [DOI:10.3802/jgo.2019.30.e13] [PMID]
  22. Djordjevic B, Westin S, Broaddus RR. Application of immunohistochemistry and molecular diagnostics to clinically relevant problems in endometrial cancer. Surg Pathol Clin. 2012;5(4):859-78. [DOI:10.1016/j.path.2012.08.004] [PMID]
  23. Ohkouchi T, Sakuragi N, Watari H, Nomura E, Todo Y, Yamada H, Fujimoto S. Prognostic significance of Bcl-2, p53 overexpression, and lymph node metastasis in surgically staged endometrial carcinoma. Am J Obstet Gynecol. 2002;187(2):353-9. [DOI:10.1067/mob.2002.123203] [PMID]
  24. Erdem O, Erdem M, Dursun A, Akyol G, Erdem A. Angiogenesis, p53, and bcl-2 expression as prognostic indicators in endometrial cancer: comparison with traditional clinicopathologic variables.  Int J Gynecol Pathol. 2003;22(3):254-60. [DOI:10.1097/01.PGP.0000070850.25718.A5] [PMID]
  25. Hirschowitz L, Ganesan R, McCluggage WG. WT1, p53 and hormone receptor expression in uterine serous carcinoma. Histopathology. 2009;55(4):478-82. [DOI:10.1111/j.1365-2559.2009.03390.x] [PMID]
  26. Mariani A, Sebo TJ, Webb MJ, Riehle D, Katzmann JA, Keeney GL, Roche PC, Lesnick TG, Podratz KC. Molecular and histopathologic predictors of distant failure in endometrial cancer. Cancer Detection Prev. 2003;27(6):434-41. [DOI:10.1016/j.cdp.2003.09.005] [PMID]
  27. Sheffield BS. Immunohistochemistry as a practical tool in molecular pathology. Arch Pathol Lab Med. 2016;140(8):766-9. [DOI:10.5858/arpa.2015-0453-RA] [PMID]
  28. Fadare O, Desouki MM, Gwin K, Hanley KZ, Jarboe EA, Liang SX, Quick CM, Zheng W, Parkash V, Hecht JL. Frequent expression of napsin A in clear cell carcinoma of the endometrium: potential diagnostic utility. Am J Surg Pathol. 2014;38(2):189-96. [DOI:10.1097/PAS.0000000000000085] [PMID]
  29. Daniilidou K, Frangou-Plemenou M, Grammatikakis J, Grigoriou O, Vitoratos N, Kondi-Pafiti A. Prognostic significance and diagnostic value of PTEN and p53 expression in endometrial carcinoma. A retrospective clinicopathological and immunohistochemical study. J Buon. 2013;18(1):195-201.
  30. Köbel M, Ronnett BM, Singh N, Soslow RA, Gilks CB, McCluggage WG. Interpretation of P53 immunohistochemistry in endometrial carcinomas: toward increased reproducibility. Int J Gynecol Pathol. 2019;38(1 Suppl 1):S123. [DOI:10.1097/PGP.0000000000000488] [PMID]
  31. McCluggage WG, Soslow RA, Gilks CB. Patterns of p53 immunoreactivity in endometrial carcinomas:‘all or nothing’staining is of importance. Histopathology. 2011;59(4):786-8. [DOI:10.1111/j.1365-2559.2011.03907.x] [PMID]
  32. Yemelyanova A, Vang R, Kshirsagar M, Lu D, Marks MA, Shih IM, Kurman RJ. Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis. Mod Pathol. 2011;24(9):1248-53. [DOI:10.1038/modpathol.2011.85] [PMID]
  33. Hernandez-Caballero AI, Vierkoetter KR, Ahn HJ, Shimizu D, Terada K. Novel immunohistochemical markers in the differential diagnosis of endocervical and endometrial adenocarcinoma: The added benefit of CAIX and PAX8. Gynecol Oncol Rep. 2020;33:100614. [DOI:10.1016/j.gore.2020.100614] [PMID]
  34. Nili F, Tavakoli M, Mood NI, Saffar H, Sarmadi S. Napsin-a expression, a reliable immunohistochemical marker for diagnosis of ovarian and endometrial clear cell carcinomas. Iran J Pathol. 2020;15(2):81. [DOI:10.30699/ijp.2020.106598.2222] [PMID]

Al-Maghrabi JA, Butt NS, Anfinan N, Sait K, Sait H, Marzouki A, Khabaz MN. Infrequent immunohistochemical expression of napsin A in endometrial carcinomas. Appl Immunohistochem Mol Morphol. 2017;25(9):632-8. [DOI:10.1097/PAI.0000000000000350] [PMID]

Iranian Journal of Pathology
Volume 19, Issue 2
Spring 2024
Pages 236-243

  • Receive Date 09 August 2023
  • Revise Date 13 September 2023
  • Accept Date 13 September 2023

Home

Guide for Authors

Submit Manuscript

Contact Us