CXCR4 表达和癌症相关成纤维细胞可能在低级别子宫内膜样癌的侵袭中发挥重要作用

IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY International Journal of Gynecological Pathology Pub Date : 2024-11-01 Epub Date: 2024-01-22 DOI:10.1097/PGP.0000000000001015
Chihiro Fukumitsu, Sakiko Sanada, Sachiko Ogasawara, Naotake Tsuda, Kenta Murotani, Mayuka Akao, Kimio Ushijima, Jun Akiba, Hirohisa Yano
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引用次数: 0

摘要

分化良好的子宫内膜样癌(EC)是一种低分化癌症,症状相对较轻。然而,即使是组织学分化良好的子宫内膜样癌,有时也倾向于广泛浸润并显示出转移潜力,这表明这是一组行为异质性的癌症。相反,由于其发病年龄较小,EC的治疗策略通常会考虑保留生育能力,这就强调了通过活检和影像诊断对子宫肌层受侵情况进行更准确评估的必要性。我们以前曾报道过CXCR4-CXCL12和CXCL14轴参与了EC的侵袭。因此,我们研究了CXCR4的表达是否能反映侵袭潜力,并探讨了它与肿瘤微环境中产生趋化因子的癌症相关成纤维细胞的相互作用。对71例EC(14例局限于子宫内膜的EC和57例肌浸润性EC)、6例子宫内膜上皮内瘤变和42例非癌变病例中CXCR4的免疫组化表达进行了评估。肌层浸润性癌细胞中CXCR4的表达明显高于非癌性癌细胞、子宫内膜上皮内瘤变和子宫内膜封闭性癌细胞。通过单变量和多变量分析,CXCR4的表达明显反映了子宫肌层的侵袭情况。活检标本和切除标本中的CXCR4表达呈弱正相关。在癌症相关成纤维细胞条件培养基中培养了一个EC细胞系,进行了侵袭和伤口愈合试验。侵袭和伤口愈合潜能取决于 CXCR4 和癌相关成纤维细胞。我们的研究表明,CXCR4 的表达是子宫肌瘤侵袭的一个独立因素,可支持活检样本治疗前的诊断评估。
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CXCR4 Expression and Cancer-associated Fibroblasts May Play an Important Role in the Invasion of Low-grade Endometrioid Carcinoma.

Well-differentiated endometrioid carcinoma (EC) is a low-grade cancer with relatively indolent behavior. However, even with well-differentiated histology, it sometimes tends to invade extensively and shows metastatic potential, suggesting that this is a group of cancers with heterogeneous behavior. In contrast, due to its tendency for younger onset, the treatment strategy for EC frequently considers fertility preservation, highlighting the need for a more accurate evaluation of myometrial invasion through biopsy and imaging diagnostics. We previously reported the involvement of the CXCR4-CXCL12 and CXCL14 axes in EC invasion. Accordingly, we investigated whether CXCR4 expression could reflect invasive potential and explored its interaction with cancer-associated fibroblasts that produce chemokines in the tumor microenvironment. Immunohistochemical expression of CXCR4 was assessed in 71 cases of EC (14 of EC confined to the endometrium and 57 of myoinvasive EC), 6 cases of endometrial intraepithelial neoplasia, and 42 cases of noncarcinomatous conditions. CXCR4 expression was significantly higher in myoinvasive EC than in noncancerous conditions, endometrial intraepithelial neoplasia, and endometrium-confined EC. By univariate and multivariate analysis, CXCR4 expression significantly reflected myometrial invasion. CXCR4 expression in the biopsied and resected specimens correlated weakly positively. Invasion and wound-healing assays were performed culturing an EC cell line in a cancer-associated fibroblast-conditioned medium. The invasion and wound-healing potentials were dependent on CXCR4 and cancer-associated fibroblast. Our study demonstrated that CXCR4 expression is an independent factor in myometrial invasion and can support diagnostic evaluation before treatment in the biopsy sample.

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来源期刊
CiteScore
3.90
自引率
12.50%
发文量
154
审稿时长
6-12 weeks
期刊介绍: International Journal of Gynecological Pathology is the official journal of the International Society of Gynecological Pathologists (ISGyP), and provides complete and timely coverage of advances in the understanding and management of gynecological disease. Emphasis is placed on investigations in the field of anatomic pathology. Articles devoted to experimental or animal pathology clearly relevant to an understanding of human disease are published, as are pathological and clinicopathological studies and individual case reports that offer new insights.
期刊最新文献
CXCR4 Expression and Cancer-associated Fibroblasts May Play an Important Role in the Invasion of Low-grade Endometrioid Carcinoma. Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study. Adenoid Cystic Carcinoma of the Vulva and Vagina: A Clinicopathologic, Immunohistochemical, and Molecular Characterization of Five Cases. Clinical Significance of Tumor Immune Microenvironment in Endometrial Endometrioid Carcinoma, Grade 1 With DNA Mismatch Repair Protein Loss. Novel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications.
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