Immunohistochemistry: A diagnostic aid in differentiating primary epithelial ovarian tumors and tumors metastatic to the ovary

Divya Kriplani; Mandakini M. Patel

doi:10.4103/2278-330x.119888

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THROUGH THE MICROSCOPE: Original Article

02 (

); 254-258

doi:

10.4103/2278-330x.119888

Immunohistochemistry: A diagnostic aid in differentiating primary epithelial ovarian tumors and tumors metastatic to the ovary

Divya Kriplani^1,, Mandakini M. Patel¹

1 Department of Pathology, Government Medical College, Surat, Gujarat, India

*Corresponding author: Dr. Divya Kriplani. divya_krips@yahoo.co.in

Published: 2020-12-31

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Abstract

Introduction: Among cancers of the female genital tract, the incidence of ovarian cancer ranks below only carcinoma of the cervix and the endometrium. Recent years have witnessed significant development in the use of immunohistochemistry in diagnostic ovarian pathology. Materials and Methods: We received 95 specimens and biopsies of primary ovarian neoplasms and neoplasms metastatic to the ovary in a period of 2 years. Of these 30 cases were of the primary surface epithelial neoplasms and seven of metastatic tumors. Discussion: The most common tumors metastasizing to the ovary originate from the gastrointestinal tract followed by the endometrium. We used a panel of six markers including cytokeratin-7 (CK7), CK20, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), estrogen receptor (ER) and Wilms’ tumor 1 (WT1) to help classify various surface epithelial tumors as well as to differentiate them from tumors metastatic to the ovary. Conclusion: CK7 is the most helpful marker to differentiate primary ovarian carcinoma from metastatic colorectal carcinoma of the ovary. Nearly, 96% of ovarian adenocarcinomas were positive for CK7 in contrast to metastatic colorectal, which showed only 25% positivity. We also found that CK7, CK20 and CEA are useful markers to differentiate primary serous tumors from primary mucinous tumors; however, these are less helpful in differentiating ovarian mucinous adenocarcinomas from colorectal adenocarcinomas metastasizing to the ovaries. WT1 helps in typing primary surface epithelial tumors of the ovary and is also significant in determining whether a serous carcinoma within the ovary is primary or metastatic.

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References

Ellenson LH, Pirog EC. The female genital tract-ovaries. In: Kumar V, Abbas AK, Fausto N, Aster JC, editors. Robbins and Cotran Pathological Basis of Disease. 8th ed. Elsevier; 2010. p. 1039-52.
Tavassoli FA, Devilee P, editors. World Health Organisation classification of tumors. Pathology and Genetics of tumors of the breast and female genital organs. IARC Press: Lyon 2003.
Mittal K, Soslow R, McCluggage WG. Application of immunohistochemistry to gynecologic pathology. Arch Pathol Lab Med 2008;132:402-23.
McCluggage WG, Young RH. Immunohistochemistry as a diagnostic aid in the evaluation of ovarian tumors. Semin Diagn Pathol 2005;22:3-32.
Koonings PP, Campbell K, Mishell DR Jr, Grimes DA. Relative frequency of primary ovarian neoplasms: A 10-year review. Obstet Gynecol 1989;74:921-6.
Wauters CC, Smedts F, Gerrits LG, Bosman FT, Ramaekers FC. Keratins 7 and 20 as diagnostic markers of carcinomas metastatic to the ovary. Hum Pathol 1995;26:852-5.
Berezowski K, Stastny JF, Kornstein MJ. Cytokeratins 7 and 20 and carcinoembryonic antigen in ovarian and colonic carcinoma. Mod Pathol 1996;9:426-9.
Ueda G, Sawada M, Ogawa H, Tanizawa O, Tsujimoto M. Immunohistochemical study of cytokeratin 7 for the differential diagnosis of adenocarcinomas in the ovary. Gynecol Oncol 1993;51:219-23.
Lagendijk JH, Mullink H, Van Diest PJ, Meijer GA, Meijer CJ. Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry: Differential diagnosis between colonic and ovarian carcinomas as primary sites. Hum Pathol 1998;29:491-7.
Dionigi A, Facco C, Tibiletti MG, Bernasconi B, Riva C, Capella C. Ovarian metastases from colorectal carcinoma. Clinicopathologic profile, immunophenotype, and karyotype analysis. Am J Clin Pathol 2000;114:111-22.
Vang R, Gown AM, Wu LS, Barry TS, Wheeler DT, Yemelyanova A, et al. Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the ovary: Comparison with CK20 and correlation with coordinate expression of CK7. Mod Pathol 2006;19:1421-8.
Logani S, Oliva E, Arnell PM, Amin MB, Young RH. Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma. Mod Pathol 2005;18:19-25.
Larson L-I, editor. Immunocytochemistry Theory and Practice. Boca Raton, FL: CRC Press; 1988.
Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: A survey of 435 cases. Mod Pathol 2000;13:962-72.
Wang NP, Zee S, Zarbo RJ, Bacchi CE, Gown AM. Coordinate expression of Cytokeratins 7 and 20 defines unique subsets of carcinomas. Appl Immunohistochem 1995;3:99-107.
Baker PM, Oliva E. Immunohistochemistry as a tool in the differential diagnosis of ovarian tumors: An update. Int J Gynecol Pathol 2005;24:39-55.
Goldstein NS, Bassi D, Uzieblo A. WT1 is an integral component of an antibody panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms. Am J Clin Pathol 2001;116:246-52.
Rekhi B, George S, Madur B, Chinoy RF, Dikshit R, Maheshwari A. Clinicopathological features and the value of differential cytokeratin 7 and 20 expression in resolving diagnostic dilemmas of ovarian involvement by colorectal adenocarcinoma and vice-versa. Diagn Pathol 2008;3:39.
Loy TS, Quesenberry JT, Sharp SC. Distribution of CA 125 in adenocarcinomas. An immunohistochemical study of 481 cases. Am J Clin Pathol 1992;98:175-9.
Burges A, Brüning A, Dannenmann C, Blankenstein T, Jeschke U, Shabani N, et al. Prognostic significance of estrogen receptor alpha and beta expression in human serous carcinomas of the ovary. Arch Gynecol Obstet 2010;281:511-7.
Karaferic A, Jovanovic D, Jelic S. Expression of HER2/neu, estrogen and progesterone receptors, CA 125 and CA19-9 on cancer cell membrane in patients with serous and mucinous carcinoma of the ovary. J BUON 2009;14:635-9.
Cathro HP, Stoler MH. The utility of calretinin, inhibin, and WT1 immunohistochemical staining in the differential diagnosis of ovarian tumors. Hum Pathol 2005;36:195-201.
Goldstein NS, Uzieblo A. WT1 immunoreactivity in uterine papillary serous carcinomas is different from ovarian serous carcinomas. Am J Clin Pathol 2002;117:541-5.
Al-Hussaini M, Stockman A, Foster H, McCluggage WG. WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma. Histopathology 2004;44:109-15.
Hylander B, Repasky E, Shrikant P, Intengan M, Beck A, Driscoll D, et al. Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer. Gynecol Oncol 2006;101:12-7.

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[1] Ellenson LH, Pirog EC. The female genital tract-ovaries. In: Kumar V, Abbas AK, Fausto N, Aster JC, editors. Robbins and Cotran Pathological Basis of Disease. 8th ed. Elsevier; 2010. p. 1039-52.

[2] Tavassoli FA, Devilee P, editors. World Health Organisation classification of tumors. Pathology and Genetics of tumors of the breast and female genital organs. IARC Press: Lyon 2003.

[3] Mittal K, Soslow R, McCluggage WG. Application of immunohistochemistry to gynecologic pathology. Arch Pathol Lab Med 2008;132:402-23.

[4] McCluggage WG, Young RH. Immunohistochemistry as a diagnostic aid in the evaluation of ovarian tumors. Semin Diagn Pathol 2005;22:3-32.

[5] Koonings PP, Campbell K, Mishell DR Jr, Grimes DA. Relative frequency of primary ovarian neoplasms: A 10-year review. Obstet Gynecol 1989;74:921-6.

[6] Wauters CC, Smedts F, Gerrits LG, Bosman FT, Ramaekers FC. Keratins 7 and 20 as diagnostic markers of carcinomas metastatic to the ovary. Hum Pathol 1995;26:852-5.

[7] Berezowski K, Stastny JF, Kornstein MJ. Cytokeratins 7 and 20 and carcinoembryonic antigen in ovarian and colonic carcinoma. Mod Pathol 1996;9:426-9.

[8] Ueda G, Sawada M, Ogawa H, Tanizawa O, Tsujimoto M. Immunohistochemical study of cytokeratin 7 for the differential diagnosis of adenocarcinomas in the ovary. Gynecol Oncol 1993;51:219-23.

[9] Lagendijk JH, Mullink H, Van Diest PJ, Meijer GA, Meijer CJ. Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry: Differential diagnosis between colonic and ovarian carcinomas as primary sites. Hum Pathol 1998;29:491-7.

[10] Dionigi A, Facco C, Tibiletti MG, Bernasconi B, Riva C, Capella C. Ovarian metastases from colorectal carcinoma. Clinicopathologic profile, immunophenotype, and karyotype analysis. Am J Clin Pathol 2000;114:111-22.

[11] Vang R, Gown AM, Wu LS, Barry TS, Wheeler DT, Yemelyanova A, et al. Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and metastatic mucinous carcinomas involving the ovary: Comparison with CK20 and correlation with coordinate expression of CK7. Mod Pathol 2006;19:1421-8.

[12] Logani S, Oliva E, Arnell PM, Amin MB, Young RH. Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma. Mod Pathol 2005;18:19-25.

[13] Larson L-I, editor. Immunocytochemistry Theory and Practice. Boca Raton, FL: CRC Press; 1988.

[14] Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: A survey of 435 cases. Mod Pathol 2000;13:962-72.

[15] Wang NP, Zee S, Zarbo RJ, Bacchi CE, Gown AM. Coordinate expression of Cytokeratins 7 and 20 defines unique subsets of carcinomas. Appl Immunohistochem 1995;3:99-107.

[16] Baker PM, Oliva E. Immunohistochemistry as a tool in the differential diagnosis of ovarian tumors: An update. Int J Gynecol Pathol 2005;24:39-55.

[17] Goldstein NS, Bassi D, Uzieblo A. WT1 is an integral component of an antibody panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms. Am J Clin Pathol 2001;116:246-52.

[18] Rekhi B, George S, Madur B, Chinoy RF, Dikshit R, Maheshwari A. Clinicopathological features and the value of differential cytokeratin 7 and 20 expression in resolving diagnostic dilemmas of ovarian involvement by colorectal adenocarcinoma and vice-versa. Diagn Pathol 2008;3:39.

[19] Loy TS, Quesenberry JT, Sharp SC. Distribution of CA 125 in adenocarcinomas. An immunohistochemical study of 481 cases. Am J Clin Pathol 1992;98:175-9.

[20] Burges A, Brüning A, Dannenmann C, Blankenstein T, Jeschke U, Shabani N, et al. Prognostic significance of estrogen receptor alpha and beta expression in human serous carcinomas of the ovary. Arch Gynecol Obstet 2010;281:511-7.

[21] Karaferic A, Jovanovic D, Jelic S. Expression of HER2/neu, estrogen and progesterone receptors, CA 125 and CA19-9 on cancer cell membrane in patients with serous and mucinous carcinoma of the ovary. J BUON 2009;14:635-9.

[22] Cathro HP, Stoler MH. The utility of calretinin, inhibin, and WT1 immunohistochemical staining in the differential diagnosis of ovarian tumors. Hum Pathol 2005;36:195-201.

[23] Goldstein NS, Uzieblo A. WT1 immunoreactivity in uterine papillary serous carcinomas is different from ovarian serous carcinomas. Am J Clin Pathol 2002;117:541-5.

[24] Al-Hussaini M, Stockman A, Foster H, McCluggage WG. WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma. Histopathology 2004;44:109-15.

[25] Hylander B, Repasky E, Shrikant P, Intengan M, Beck A, Driscoll D, et al. Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer. Gynecol Oncol 2006;101:12-7.

Immunohistochemistry: A diagnostic aid in differentiating primary epithelial ovarian tumors and tumors metastatic to the ovary

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Abstract

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