CXCL14-CXCR4 and CXCL12-CXCR4 Axes May Play Important Roles in the Unique Invasion Process of Endometrioid Carcinoma With MELF-Pattern Myoinvasion
The term “MELF-pattern myometrial invasion” (MELF pattern) denotes an unusual morphology of myometrial invasion in endometrioid carcinomas, and is associated with frequent lymphovascular invasion and lymph node metastasis. In this study, tumor cells were directly collected from a MELF pattern site, using laser microdissection. Comprehensive microarray analysis of the genes was conducted, and based on the results, expression of a metastasis progression gene, CXCR4, and its ligands CXCL14 and CXCL12, was further investigated. In vitro studies of endometrioid carcinoma cell lines revealed elevated invasion activity in a manner dependent on the CXCL14-CXCR4 or CXCL12-CXCR4 axis. Immunohistochemical analysis of 93 (MELF group, 46; non-MELF group, 47) cases illustrated CXCR4 was expressed in all endometrioid carcinomas, while based on CXCL14 and CXCL12 expression score, high proportions of cells were positive at the sites of the MELF pattern (P<0.01). There was no significant difference in progression-free survival or overall survival between MELF group and non-MELF group by Kaplan-Meier analysis. These findings suggest a possibility that cells at the sites of MELF pattern had acquired increased invasiveness through the function of the CXCL14-CXCR4 and CXCL12-CXCR4 axes.