Mesothelin (MSLN) is expressed in the mesothelium in normal tissues but is overexpressed in various malignant tumors. In this study, we searched for genes that were more frequently expressed in cases of endometrioid carcinoma (EC) with the MELF (microcystic, elongated, and fragmented) pattern using laser microdissection and RNA sequencing, and found that MSLN was predominantly expressed in cases with the MELF pattern. The role of MSLN in EC was analyzed by generating MSLN-knockout and -knockdown EC cell lines. MSLN promoted migration and epithelial-mesenchymal transition (EMT). Moreover, we found that cadherin-6 (CDH6) expression was regulated by MSLN. MSLN is known to bind to cancer antigen 125 (CA125), and we found that CA125 can regulate CDH6 expression via MSLN. Immunohistochemical investigations showed that MSLN, CA125, and CDH6 expression levels were considerably elevated in EC with the MELF pattern. The expression of CA125 was similar to that of MSLN not only in terms of immunohistochemical staining intensity but also the blood level of CA125. Our results showed that MSLN contributes to the migration and EMT of EC cells through upstream CA125 and downstream CDH6. Therefore, MSLN has potential as a therapeutic target for EC with the MELF pattern.
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http://dx.doi.org/10.1016/j.prp.2024.155562 | DOI Listing |
Pathol Res Pract
December 2024
Department of Pathology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan. Electronic address:
One of the known histological patterns of endometrioid carcinoma (EC) in uterine corpus cancer is MELF (microcystic, elongated, and fragmented). MELF is associated with lymphovascular invasion and lymph node metastasis. Besides MELF, it is also known that squamous differentiation (SD) often occurs in EC.
View Article and Find Full Text PDFBMC Womens Health
November 2024
Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
Objective: To assess the characteristics, molecular classification, and role of adjuvant treatment in patients with endometrioid endometrial cancer (EEC) and microcystic elongated and fragmented (MELF) myometrial invasion pattern.
Methods: This study included patients who were diagnosed with EEC with a MELF invasion pattern and underwent surgery from January 2019 to December 2023. We analyzed molecular classification, clinicopathological characteristics, and prognostic outcomes, including recurrence and adjuvant therapy.
Cancers (Basel)
October 2024
Department of Pathology, Peking University People's Hospital, Beijing 100044, China.
Pathol Res Pract
October 2024
Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address:
Mesothelin (MSLN) is expressed in the mesothelium in normal tissues but is overexpressed in various malignant tumors. In this study, we searched for genes that were more frequently expressed in cases of endometrioid carcinoma (EC) with the MELF (microcystic, elongated, and fragmented) pattern using laser microdissection and RNA sequencing, and found that MSLN was predominantly expressed in cases with the MELF pattern. The role of MSLN in EC was analyzed by generating MSLN-knockout and -knockdown EC cell lines.
View Article and Find Full Text PDFInt J Gynecol Pathol
July 2024
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Faculty of Medicine, Sitki Koçman University, Muğla, Turkey.
Several types of myometrial invasion in endometrioid-type endometrial adenocarcinoma (EEC) have been identified: adenomyosis-like changes; adenoma malignum; broad front, single-cell/cell clusters; and the microcystic elongated and fragmented (MELF) pattern. This study aims to investigate the effect of the MELF pattern on recurrence type and survival rate among patients with EEC. We retrospectively reviewed the records of patients diagnosed with EEC over a 10-year period from January 2011 to January 2021.
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