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Diagnostic Accuracy of Alpha-Methylacyl-CoA Racemase Immunohistochemical Expression for the Diagnosis of Ovarian and Endometrial Clear Cell Carcinomas

Document Type : Original Research

Authors

1 Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Pathology, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background & Objective: Clear cell carcinoma (CCC) is an uncommon histopathologic subtype of ovarian and endometrial carcinoma. Due to the morphologic overlapping with other subtypes of ovarian and endometrial carcinomas, an accurate diagnosis is crucial.
Methods: In this study, 31 cases of ovarian clear cell carcinoma (OCCC), 28 endometrial clear cell carcinoma (ECCC), and 80 non-CCC subtypes (33 high-grade serous carcinomas of the ovary, 2 low-grade serous carcinomas, 10 ovarian endometrioid, 3 serous carcinomas and 29 endometrioid carcinomas of the endometrium) were investigated for immunohistochemical expression of AMACR. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the distinction of OCCC and ECCC from other histopathologic subtypes were calculated.
Results: Positive AMACR staining was seen in 18 OCCCs (58%) and 10 ECCCs (35.7%). In the non-clear cell group, 44 cases of ovarian (98%) and 25 cases of endometrial carcinoma (78%) showed negative results. Only one case of ovarian endometrioid carcinoma and 7 cases (22%) of endometrial endometrioid carcinomas revealed a positive reaction (P<0.05). Collectively, sensitivity, specificity, PPV, and NPV of AMACR expression, for the diagnosis of OCCC were calculated as  58%, 98%, 94.7%, and 77.2%, respectively. The sensitivity, specificity, PPV, and NPV were shown to be as  35.7%, 78.1%, 58.8%, and 58.1%, respectively in the endometrium.
Conclusion: AMACR may be  a highly specific immunohistochemical marker for the distinction of serous and clear cell carcinoma. A small percentage of endometrioid carcinoma may show positive staining. The sensitivity of this marker may not be higher than the other well-known Napsin-A IHC marker.

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References
  1. Gadducci A, Multinu F, Cosio S, Carinelli S, Ghioni M, Aletti GD. Clear cell carcinoma of the ovary: Epidemiology, pathological and biological features, treatment options and clinical outcomes. Gynecol Oncol. 2021;162(3):741-50. [DOI:10.1016/j.ygyno.2021.06.033] [PMID]
  2. Kobel M BJ, Cheung AN, Deliar DF, Kiyokawa T, Shin I. clear cell carcinoma of the ovary. WHO classification of female genital tract tumors. 5 ed2020.
  3. Gaona-Luviano P, Medina-Gaona LA, Magana-Perez K. Epidemiology of ovarian cancer. Chin Clin Oncol. 2020;9(4):47. [DOI:10.21037/cco-20-34] [PMID]
  4. Fadare O, Parkash V. Pathology of Endometrioid and Clear Cell Carcinoma of the Ovary. Surg Pathol Clin. 2019;12(2):529-64. [DOI:10.1016/j.path.2019.01.009] [PMID]
  5. Zhu C, Xu Z, Zhang T, Qian L, Xiao W, Wei H, et al. Updates of Pathogenesis, Diagnostic and Therapeutic Perspectives for Ovarian Clear Cell Carcinoma. J Cancer. 2021;12(8):2295-316. [DOI:10.7150/jca.53395] [PMID] [PMCID]
  6. Kurman RJ, Ellenson LH, Ronnett BM. Blaustein's pathology of the female genital tract: Springer; 2011. [DOI:10.1007/978-1-4419-0489-8]
  7. Nucci R. Marisa P-HC. Gynecologic pathology. 2 ed. Goldblum JR, editor: Elsevier; 2021.
  8. Rekhi B, Deodhar KK, Menon S, Maheshwari A, Bajpai J, Ghosh J, et al. Napsin A and WT 1 are useful immunohistochemical markers for differentiating clear cell carcinoma ovary from high-grade serous carcinoma. Apmis. 2018;126(1):45-55. [DOI:10.1111/apm.12784] [PMID]
  9. Evans A. α-Methylacyl CoA racemase (P504S): overview and potential uses in diagnostic pathology as applied to prostate needle biopsies. J Clin Pathol. 2003;56(12):892-7. [DOI:10.1136/jcp.56.12.892] [PMID] [PMCID]
  10. Lloyd MD, Yevglevskis M, Lee GL, Wood PJ, Threadgill MD, Woodman TJ. alpha-Methylacyl-CoA racemase (AMACR): metabolic enzyme, drug metabolizer and cancer marker P504S. Prog Lipid Res. 2013;52(2):220-30. [DOI:10.1016/j.plipres.2013.01.001] [PMID]
  11. Molinié V, Balaton A, Rotman S, Mansouri D, De Pinieux I, Homsi T, et al. Alpha-methyl CoA racemase expression in renal cell carcinomas. Hum Pathol. 2006;37(6):698-703. [DOI:10.1016/j.humpath.2006.01.012] [PMID]
  12. Alshenawy HA. Immunohistochemical panel for differentiating renal cell carcinoma with clear and papillary features. J Microsc Ultrastruct. 2015;3(2):68-74. [PMID] [PMCID] [DOI:10.1016/j.jmau.2015.01.003]
  13. Kourda N, Mlika M, Derouiche A, Zidi-Moaffak Y, Chebil M, Zermani R, et al. The utility of alpha-methyl CoA racemase (P504S) expression as a marker of renal cell carcinomas. Tunisie Med. 2010;88(9):651-4.
  14. Soslow RA. High‐grade endometrial carcinomas-strategies for typing. Histopathology. 2013;62(1):89-110. [DOI:10.1111/his.12029] [PMID]
  15. Gilks CB, Oliva E, Soslow RA. Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma. Am J Surg Pathol. 2013;37(6):874-81. [PMID] [DOI:10.1097/PAS.0b013e31827f576a]
  16. Fadare O, Zhao C, Khabele D, Parkash V, Quick CM, Gwin K, et al. Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase (AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma: an immunohistochemical study of 279 ovarian tumours. Pathology. 2015;47(2):105-11. [DOI:10.1097/PAT.0000000000000223] [PMID]
  17. Fadare O, Parkash V, Gwin K, Hanley KZ, Jarboe EA, Liang SX, Quick CM, Zheng W, Rawish KR, Hecht JL, Desouki MM. Utility of α-methylacyl-coenzyme-A racemase (p504s) immunohistochemistry in distinguishing endometrial clear cell carcinomas from serous and endometrioid carcinomas. Hum Pathol.. 2013;44(12):2814-21. [DOI:10.1016/j.humpath.2013.07.033] [PMID] [PMCID]
  18. Fadare O, Parkash V, Dupont WD, Acs G, Atkins KA, Irving JA, et al. The diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists: an assessment of interobserver variability and associated morphologic features. Am J Surg Pathol. 2012;36(8):1107-18. [PMID] [DOI:10.1097/PAS.0b013e31825dd4b3]
  19. Han G, Soslow RA, Wethington S, Levine DA, Bogomolniy F, Clement PB, et al. Endometrial carcinomas with clear cells: a study of a heterogeneous group of tumors including interobserver variability, mutation analysis, and immunohistochemistry with HNF-1β. Int J Gynecoll Pathol. 2015;34(4):323-33. [PMID][DOI:10.1097/PGP.0000000000000162]
  20. ARCIUOLO D, TRAVAGLINO A, RAFFONE A, SANTORO A, INZANI F, PIERMATTEI A, et al. P504S/alpha-Methylacyl-CoA racemase, HNF1β and Napsin A in morular metaplasia and clear cell carcinoma of the endometrium: an immunohistochemical analysis. Pathol Res Pract. 2022:153953. [DOI:10.1016/j.prp.2022.153953] [PMID]
  21. Pors J, Segura S, Cheng A, Ji JX, Tessier-Cloutier B, Cochrane D, et al. Napsin-A and AMACR are superior to HNF-1β in distinguishing between mesonephric carcinomas and clear cell carcinomas of the gynecologic tract. Appl Immunohistochemist Molecul Morphol. 2020;28(8):593. [PMCID] [DOI:10.1097/PAI.0000000000000801] [PMID]
  22. Went PT, Sauter G, Oberholzer M, Bubendorf L. Abundant expression of AMACR in many distinct tumour types. Pathology. 2006;38(5): 426-32. [DOI:10.1080/00313020600922470] [PMID]
  23. Tretiakova MS, Sahoo S, Takahashi M, Turkyilmaz M, Vogelzang NJ, Lin F, et al. Expression of alpha-methylacyl-CoA racemase in papillary renal cell carcinoma. Am J Surg Pathol. 2004;28(1):69-76. [PMID] [DOI:10.1097/00000478-200401000-00007]
  24. Kato N, Sasou S, Motoyama T. Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary. Mod Pathol. 2006;19(1):83-9. [DOI:10.1038/modpathol.3800492] [PMID]
  25. Tsuchiya A, Sakamoto M, Yasuda J, Chuma M, Ohta T, Ohki M, et al. Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1β as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma. Am J Pathol. 2003;163(6):2503-12. [PMID] [DOI:10.1016/S0002-9440(10)63605-X]
  26. Fadare O, Liang SX. Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma. Appl Immunohistochem Mol Morphol. 2012;20(6):580-7. [PMID] [DOI:10.1097/PAI.0b013e31824973d1]
  27. Yamamoto S, Tsuda H, Aida S, Shimazaki H, Tamai S, Matsubara O. Immunohistochemical detection of hepatocyte nuclear factor 1β in ovarian and endometrial clear-cell adenocarcinomas and nonneoplastic endome-trium. Hum Pathol. 2007;38(7):1074-80. [DOI:10.1016/j.humpath.2006.12.018] [PMID]
  28. Fadare O, Desouki MM, Gwin K, Hanley KZ, Jarboe EA, Liang SX, et al. Frequent expression of napsin A in clear cell carcinoma of the endometrium: potential diagnostic utility. Am J Surg Pathol. 2014;38(2):189-96. [PMID] [DOI:10.1097/PAS.0000000000000085]
  29. Nili F, Tavakoli M, Izadi Mood N, 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):81-5. [DOI:10.30699/ijp.2020.106598.2222] [PMID] [PMCID]
  30. Iwamoto M, Nakatani Y, Fugo K, Kishimoto T, Kiyokawa T. Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium. Hum Pathol. 2015;46(7):957-62. [DOI:10.1016/j.humpath.2015.03.008] [PMID]
  31. Skirnisdottir I, Bjersand K, Åkerud H, Seidal T. Napsin A as a marker of clear cell ovarian carcinoma. BMC Cancer. 2013;13(1):1-12. [DOI:10.1186/1471-2407-13-524] [PMID] [PMCID]
Iranian Journal of Pathology
Volume 18, Issue 1
January 2023
Pages 57-63
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History
  • Receive Date: 06 July 2022
  • Accept Date: 16 November 2022
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