Expression of CLDN18.2, CDX2, SATB2, and PAX8 in Primary and Gastrointestinal-Derived Mucinous Ovarian Carcinoma
Download PDF
$currentUrl="http://$_SERVER[HTTP_HOST]$_SERVER[REQUEST_URI]"

Keywords

Mucinous ovarian carcinoma
Gastrointestinal-derived mucinous ovarian carcinoma
CLDN18.2
Immunohistochemistry
Differential diagnosis

DOI

10.26689/aogr.v3i3.11130

Submitted : 2025-06-11
Accepted : 2025-06-26
Published : 2025-07-11

Abstract

Objective: Primary and metastatic mucinous ovarian carcinomas share similar morphologies but have significant differences in prognosis. This study aims to explore the immunophenotypic characteristics of primary and gastrointestinal-derived mucinous ovarian carcinomas. Methods: A total of 230 cases of primary and gastrointestinal-derived mucinous ovarian tumors surgically removed at Junnan County People’s Hospital and the Affiliated Hospital of Qingdao University from 2014 to 2024 were randomly selected. These included 67 cases of primary mucinous ovarian carcinoma, 56 cases of primary borderline mucinous ovarian tumor, 61 cases of colorectal-derived mucinous ovarian carcinoma (including 26 cases from the appendix and 35 cases from the colorectum), 26 cases of gastric-derived mucinous ovarian carcinoma, and 20 cases of mucinous cystadenoma of the ovary. All specimens were reviewed and confirmed by two experienced pathologists according to the 2020 WHO classification criteria. Immunohistochemistry was used to detect the expression differences of CLDN18.2 in primary mucinous ovarian tumors. Furthermore, the expressions of CLDN18.2, CDX2, SATB2, and PAX8 were jointly detected in primary and gastrointestinal metastatic mucinous ovarian tumors to explore the immunoexpression characteristics of multiple immune markers in primary ovarian and upper and lower gastrointestinal-derived ovarian metastatic mucinous carcinomas. Results: 1. CLDN18.2 showed varying degrees of expression in mucinous cystadenoma of the ovary, borderline mucinous ovarian tumor, and primary mucinous ovarian carcinoma, but was not expressed in normal ovarian and fallopian tube tissues. 2. In primary mucinous ovarian carcinoma, CLDN18.2 and PAX8 showed high expression, while CDX2 and SATB2 showed lower expression. In gastric-derived mucinous ovarian carcinoma, CLDN18.2 and CDX2 showed high expression, while SATB2 and PAX8 were almost not expressed. In colorectal-derived mucinous ovarian carcinoma, CDX2 and SATB2 showed high expression, while CLDN18.2 and PAX8 showed low expression. Conclusion: CLDN18.2 shows high expression in both primary and gastric-derived mucinous ovarian carcinomas and can be used as an auxiliary method for differentiating primary and gastrointestinal-derived mucinous ovarian carcinomas along with CDX2, SATB2, and PAX8.

References

Menon U, Karpinskyj C, Gentry-Maharaj A, 2018, Ovarian Cancer Prevention and Screening. Obstetrics and Gynecology, 131(5): 909–927.

Kossai M, Leary A, Scoazec J, et al., 2018, Ovarian Cancer: A Heterogeneous Disease. Pathobiology, 85(1–2): 41–49.

Heinzelmann-Schwarz V, Gardiner-Garden M, Henshall S, et al., 2006, A Distinct Molecular Profile Associated with Mucinous Epithelial Ovarian Cancer. British Journal of Cancer, 94(6): 904–913.

Lheureux S, Gourley C, Vergote I, et al., 2019, Epithelial Ovarian Cancer. The Lancet, 393(10177): 1240–1253.

Cree I, White V, Indave B, et al., 2020, Revising the WHO Classification: Female Genital Tract Tumours. Histopathology, 76(1): 151–156.

Dundr P, Singh N, Nozickova B, et al., 2021, Primary Mucinous Ovarian Tumors vs. Ovarian Metastases from Gastrointestinal Tract, Pancreas and Biliary Tree: A Review of Current Problematics. Diagnostic Pathology, 16(1): 20.

Kubecek O, Laco J, Spacek J, et al., 2017, The Pathogenesis, Diagnosis, and Management of Metastatic Tumors to the Ovary: A Comprehensive Review. Clinical and Experimental Metastasis, 34(5): 295–307.

Prat J, D’Angelo E, Espinosa I, 2018, Ovarian Carcinomas: At Least Five Different Diseases with Distinct Histological Features and Molecular Genetics. Human Pathology, 80: 11–27.

English D, Santin A, 2013, Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy. International Journal of Molecular Sciences, 14(5): 10412–10437.

Tabaries S, Siegel P, 2017, The Role of Claudins in Cancer Metastasis. Oncogene, 36(9): 1176–1190.

Li J, Zhang Y, Hu D, et al., 2020, Analysis of the Expression and Genetic Alteration of CLDN18 in Gastric Cancer. Aging, 12(14): 14271–14284.

Liang J, Zhang H, Huang Y, et al., 2021, A CLDN18.2-Targeting Bispecific T Cell Co-Stimulatory Activator for Cancer Immunotherapy. Cancer Management and Research, 13: 6977–6987.

Li J, Yu Z, Hu D, et al., 2020, Analysis of the Expression and Genetic Alteration of CLDN18 in Gastric Cancer. Aging, 12(14): 14271–14284.

Halimi SA, Maeda D, Shinozaki-Ushiku A, et al., 2013, Claudin-18 Overexpression in Intestinal-Type Mucinous Borderline Tumour of the Ovary. Histopathology, 63(4): 534–544.

Halimi S, Maeda D, Ushiku-Shinozaki A, et al., 2021, Comprehensive Immunohistochemical Analysis of the Gastrointestinal and Mullerian Phenotypes of 139 Ovarian Mucinous Cystadenomas. Human Pathology, 109: 21–30.

Yu J, Liu D, Sun X, et al., 2019, CDX2 Inhibits the Proliferation and Tumor Formation of Colon Cancer Cells by Suppressing Wnt/Beta-Catenin Signaling. Cell Death and Disease, 10(1): 26.

Bayrak R, Hacıhanefioglu A, Savaş H, 2012, The Value of CDX2 and Cytokeratins 7 and 20 Expression in Differentiating Colorectal Adenocarcinomas. Diagnostic Pathology, 7: 9.

Li Z, Roth R, Rock J, et al., 2017, Dual Immunostain With SATB2 and CK20 Differentiates Appendiceal Mucinous Neoplasms From Ovarian Mucinous Neoplasms. American Journal of Clinical Pathology, 147(5): 484–491.

Aldaoud N, Erashdi M, AlKhatib S, et al., 2019, The Utility of PAX8 and SATB2 Immunohistochemical Stains in Distinguishing Ovarian Mucinous Neoplasms. BMC Research Notes, 12(1): 770.

Danialan R, Assaad M, Burghardt J, et al., 2013, The Utility of PAX8 and IMP3 Immunohistochemical Stains in the Differential Diagnosis of Benign, Premalignant, and Malignant Endocervical Glandular Lesions. Gynecologic Oncology, 130(2): 383–388.

Bowen N, Logani S, Dickerson E, et al., 2007, Emerging Roles for PAX8 in Ovarian Cancer and Endosalpingeal Development. Gynecologic Oncology, 104(2): 331–337.

Ricci F, Affatato R, Carrassa L, et al., 2018, Recent Insights Into Mucinous Ovarian Carcinoma. International Journal of Molecular Sciences, 19(6): 1569.

Morice P, Gouy S, Leary A, 2019, Mucinous Ovarian Carcinoma. New England Journal of Medicine, 380(13): 1256–1266.

Mineta K, Yamamoto Y, Yamazaki Y, et al., 2011, Predicted Expansion of the Claudin Multigene Family. FEBS Letters, 585(4): 606–612.

Athauda A, Chau I, 2021, Claudin 18.2 – A FAST-Moving Target in Gastric Cancer? Annals of Oncology, 32(5): 584–586.

Baek J, Park D, Kim G, et al., 2019, Clinical Implications of Claudin18.2 Expression in Patients With Gastric Cancer. Anticancer Research, 39(12): 6973–6979.

Kim S, Shin K, Park J, et al., 2020, Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer. Journal of Gastric Cancer, 20(4): 408–420.

Kiyokawa T, Pesci A, et al., 2021, Claudin-18 as a Promising Surrogate Marker for Endocervical Gastric-Type Carcinoma. American Journal of Surgical Pathology, 46(5): 628–636.

Kelemen L, Köbel M, 2011, Mucinous Carcinomas of the Ovary and Colorectum: Different Organ, Same Dilemma. The Lancet Oncology, 12(11): 1071–1080.

Yemelyanova A, Vang R, Judson K, et al., 2008, Distinction of Primary and Metastatic Mucinous Tumors Involving the Ovary. American Journal of Surgical Pathology, 32(1): 128–138.

Simons M, Bolhuis T, Haan A, et al., 2019, A Novel Algorithm for Better Distinction of Primary Mucinous Ovarian Carcinomas and Mucinous Carcinomas Metastatic to the Ovary. Virchows Archiv, 474(3): 289–296.

Gucer H, Caliskan S, Kefeli M, Mete O, 2020, Do You Know the Details of Your PAX8 Antibody? Endocrine Pathology, 31(1): 33–38.