Downregulation of BRG-1 repressed expression of CD44s in cervical neuroendocrine carcinoma and adenocarcinoma

Abstract

Neuroendocrine carcinomas of the uterine cervix are rare tumors with early metastases, highly aggressive clinical behavior, and poor clinical outcome. Several adhesion molecules like cadherins have been tested in an attempt to explain their unique characteristics. Cluster differentiation 44 (CD44) is a widely expressed cell surface glycoprotein that serves as an adhesion molecule in cell-to-substrate and cell-to-cell interaction. We have examined the expression of the standard CD44 (CD44s) by immunohistochemical stains in the paraffinembedded cervical neoplasm tissue of 17 cases of primary cervical neuroendocrine carcinoma, 28 cases of cervical adenocarcinoma, and 50 cases of cervical squamous cell carcinoma. Loss of CD44s expression was found in 16 of 17 neuroendocrine carcinomas, 14 of 28 adenocarcinomas, and three of 50 squamous cell carcinomas. The differences were statistically significant. We also examined immunohistochemically the expression of the BRG-1 subunit of the SWI-SNF complex, which has been reported to regulate the expression of CD44 in all cases. Loss of BRG-1 expression was observed in 12/16, 6/14, and 1/3 CD44s-negative neuroendocrine carcinomas, adenocarcinomas, and squamous cell carcinomas, respectively. This study suggests that loss of the CD44s molecule may imply special biological behaviors of cervical neuroendocrine carcinomas, and loss of expression of BRG-1 may contribute to this.

The BRG1 Chromatin Remodeler Protects Against Ovarian Cysts, Uterine Tumors, and Mammary Tumors in a Lineage-Specific Manner

“…The Brg1 Wap-Cre ovarian cyst and uterine tumor phenotype is also reminiscent of recent deep-sequencing efforts demonstrating consistent mutations of another SWI/SNF subunit, ARID1A/BAF250a , in ∼30% and ∼50% of human ovarian clear cell carcinomas and endometrial carcinomas, respectively [54], [55]. Our data also support the observation that BRG1 is downregulated in human cervical carcinomas [56]. In summary, our results add weight to the idea that SWI/SNF-related complexes have an important function in preventing the development of cancers, particularly within the stem/progenitor compartments of cells in certain tissues.…”

Glassy Cell Carcinoma Predominantly Commits to a Squamous Lineage and is Strongly Associated With High-risk Type Human Papillomavirus Infection

“…CD44, the main receptor for hyaluronan, serves as an adhesion molecule in cell-cell and cell-matrix interaction, and has widely been known in tissue regeneration and tumor dissemination (15,16). It is normally cleaved by MMP14 (MT1-MMP).…”

Abnormal Immunoexpression of Cell Adhesion Molecules (CAMs) in Cervical Cancer

“…We also observed reduced significant expression in the adenocarcinomas in comparison with SCCs probably resulting from the degree of aggression and the prognosis of each histological type of tumor. 34 It is possible that the behavior of each histological tumor type is related to the degree of CAM alteration, as in the case of neuroendocrine cervical carcinoma, where the loss of adhesion by BRG-1, 29 a regulator of CD44 expression, is involved.…”

“…2 The antigenic expression of the CD44 family and its isoforms is found to be markedly disturbed in different neoplastic gynecological tissues, including cervical cancer 5,28,29 associated with the progression and metastasis of tumors. 30,31 The CD44 family 11,32 and E-cadherin 33 can be found to be greatly altered in the lesser differentiated carcinomas.…”