Document Type: Original Research

Authors

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

2 Department of Pathology, Mohebb-e-Yas Women Hospital, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background & Objective: Clear cell carcinomas (CCC) differ from other types of ovarian and endometrial carcinomas in biology, behavior and response to chemotherapy. Histopathologic diagnosis may be challenging in some situations which necessitates immunohistochemistary (IHC) assessment. In this study we investigated the diagnostic utility of Napsin-A in diagnosis of ovarian and endometrial CCCs.
Methods: Ovarian and endometrial CCC samples from 2013 to 2018 in 3 general and women’s hospital in Tehran were re-evaluated by 2 expert pathologists. Forty-two samples were included as case and 42 non-clear cell carcinomas (Non-CCC) of ovary and endometrium were selected as control group. Based on IHC study tumors with sum intensity and percentage score ≥2 (at least 1+ staining in more than 1% of tumor cells) were considered positive.
Results: The prevalence of endometrial and ovarian CCC in the case group were 15 and 27 respectively. The tumors in the control group included 22 cases of endometrioid, 2 high grade papillary serous carcinoma (HGSC) of endometrium, 6 endometrioid and 12 HGSC of ovary. Napsin-A positivity was observed in 35 (83%) of CCCs while 7 (17%) samples including 3 out of 15 endometrial and 4 out of 27 ovarian CCCs were Napsin-A negative. No positive reaction was seen in control group. The overall accuracy, specifity and sensitivity of Napsin-A for diagnosis of ovarian and endometrial CCCs were 83%, 100% and 83%, respectively. Sensitivity for ovarian and endometrial CCCs were 85% and 80%, orderly.
Conclusion: Napsin-A is an accurate and reliable marker for distinction of CCCs from non-CCCs in ovary and endometrium. A panel of antibodies may yield the highest diagnostic accuracy.

Keywords

Main Subjects

  1. Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review. Cancer Biol Med. Chinese Anti-Cancer Association; 2017 Feb;14(1):9-32.
  2. Abdulfatah E, Sakr S, Thomas S, Al-Wahab Z, Mutch DG, Dowdy S, et al. Clear Cell Carcinoma of the Endometrium: Evaluation of Prognostic Parameters in a Multi-institutional Cohort of 165 Cases. Int J Gynecol Cancer. NIH Public Access; 2017;27(8):1714-21. [DOI:10.1097/IGC.0000000000001050]
  3. Tang H, Liu Y, Wang X, Guan L, Chen W, Jiang H, et al. Clear cell carcinoma of the ovary. Medicine (Baltimore). 2018 May;97(21):e10881. [DOI:10.1097/MD.0000000000010881]
  4. Chan JK, Teoh D, Hu JM, Shin JY, Osann K, Kapp DS. Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecol Oncol. 2008 Jun;109(3):370-6. [DOI:10.1016/j.ygyno.2008.02.006]
  5. Shu AC, Qin Z, Jotwani RA, Iasonos A, Leitao Jr MM , Konner JA, Aghajanian AC. Ovarian Clear Cell Carcinoma, Outcomes by Stage: The MSK Experience. Gynecol Oncol. 2015 ; 139(2): 236-241 [DOI:10.1016/j.ygyno.2015.09.016]
  6. Soslow RA, Bissonnette JP, Wilton A, et al. Clinicopathologic analysis of 187 high-grade endometrial carcinomas of different histologic subtypes: similar outcomes belie distinctive biologic differences. Am J Surg Pathol. 2007; 31: 979-987. [DOI:10.1097/PAS.0b013e31802ee494]
  7. Fadare O, Zheng W, Crispens MA, Jones HWI, Khabele D, Gwin K, et al. Morphologic and other clinicopathologic features of endometrial clear cell carcinoma: a comprehensive analysis of 50 rigorously classified cases. Am J Cancer Res. 2013;3(1):70-95.
  8. Fadare O, Parkash V, Dupont WD, et al. The diagnosis of endometrial carcinomas withclear cells by gynecologic pathologists: an assessment of interobserver variability andassociated morphologic features. Am J Surg Patho. 2012; 36: 1107-1118 [DOI:10.1097/PAS.0b013e31825dd4b3]
  9. Gilks CB, Oliva E, Soslow RA. Poor interobserver reproducibility in the diagnosis of high grade endometrial carcinoma. Am J Surg Pathol . 2013;37:874-881 [DOI:10.1097/PAS.0b013e31827f576a]
  10. Han G, Soslow RA, Wethington S, Levine DA, Bogomolniy F, Clement PB, et al. Endometrial Carcinomas With Clear Cells. Int J Gynecol Pathol. 2015 Jul;34(4):323-33. [DOI:10.1097/PGP.0000000000000162]
  11. Felix AS, Yang HP, Bell DW, Sherman ME. Epidemiology of Endometrial Carcinoma: Etiologic Importance of Hormonal and Metabolic Influences. In: Advances in experimental medicine and biology. 2017. p. 3-46. [DOI:10.1007/978-3-319-43139-0_1]
  12. Asadinejad E, Abdirad A, Nili F, Soleimani V. Middle East journal of cancer. Vol. 9, Middle East Journal of Cancer. Shiraz University of Medical Sciences; 2018. 300-309 p.
  13. Mutter GL, Prat JD. Pathology of the female reproductive tract. Churchil Livingstone. 3th Edition. 2014. 853 p.
  14. Sayar A, Ugras N, Adim SB, Atalay FO. Role of napsin A immunohistochemical staining in differentiating ovarian clear cell carcinoma from other ovarian epithelial tumors. Int J Clin Exp Pathol. 2016 Jan 1;9(9):9575-80.
  15. Zhu B, Rohan SM, Lin X. Immunoexpression of napsin a in renal neoplasms. Diagn Pathol. BioMed Central; 2015 Mar 14;10(1):4. [DOI:10.1186/s13000-015-0242-z]
  16. Turner BM, Cagle PT, Sainz IM, Fukuoka J, Shen SS, Jagirdar J. Napsin A, a New Marker for Lung Adenocarcinoma, Is Complementary and More Sensitive and Specific Than Thyroid Transcription Factor 1 in the Differential Diagnosis of Primary Pulmonary Carcinoma: Evaluation of 1674 Cases by Tissue Microarray. Arch Pathol Lab Med. 2012 Feb;136(2):163-71. [DOI:10.5858/arpa.2011-0320-OA]
  17. Ordonez NG. Napsin A expression in lung and kidney neoplasia: a review and update. AdvAnat Pathol. 2012;19:66-73. [DOI:10.1097/PAP.0b013e31823e472e]
  18. Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1 expression incarcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma.Hum Pathol. 2010;41:20-25. [DOI:10.1016/j.humpath.2009.06.014]
  19. 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. Am J Surg Pathol. 2014 Feb;38(2):189-96. [DOI:10.1097/PAS.0000000000000085]
  20. 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 Jul;46(7):957-62. [DOI:10.1016/j.humpath.2015.03.008]
  21. Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, et al. Napsin A is a specific marker for ovarian clear cell adenocarcinoma. Mod Pathol. Nature Publishing Group; 2015 Jan 11;28(1):111-7. [DOI:10.1038/modpathol.2014.61]
  22. Al-Maghrabi JA, Butt NS, Anfinan N, Sait K, Sait H, Marzouki A, et al. Infrequent Immunohistochemical Expression of Napsin A in Endometrial Carcinomas. Appl Immunohistochem Mol Morphol. 2017 Oct;25(9):632-8. [DOI:10.1097/PAI.0000000000000350]
  23. Alshenawy HA, Radi DA. Napsin-A, A Possible Diagnostic Marker for Differentiating Clear Cell Ovarian Carcinoma From Other High-grade Ovarian Carcinomas. Appl Immunohistochem Mol Morphol. 2017 Mar;1. [DOI:10.1097/PAI.0000000000000510]
  24. 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. John Wiley & Sons, Ltd (10.1111); 2018 Jan 1;126(1):45-55. [DOI:10.1111/apm.12784]
  25. Biesheuvel CJ, Vergouwe Y, Oudega R, Hoes AW, Grobbee DE, Moons KG. Advantages of the nested case-control design in diagnostic research. BMC Med Res Methodol. BioMed Central; 2008 Jul 21;8:48. [DOI:10.1186/1471-2288-8-48]
  26. 26. 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 Feb;47(2):105-11. [DOI:10.1097/PAT.0000000000000223]