title: Upregulation of MUC4 in cervical squamous cell carcinoma: pathologic significance.
abstract: MUC4 is a transmembrane glycoprotein more highly expressed in cervical dysplasia than benign cervical epithelium. We sought to determine whether MUC4 expression differs between benign and malignant cervical tissue. Fifty-eight patients with benign, dysplastic, or malignant cervical pathology were identified retrospectively, and representative sections were stained with a mouse monoclonal anti-MUC4 antibody. Semiquantitative analysis was performed on benign, dysplastic, and malignant regions by scoring staining intensity (0: negative, 1: weak, 2: moderate, and 3: strong) and distribution (focal <10%, multifocal=10%-60%, diffuse > or =60%). In samples with benign glycogenated squamous epithelium, only the parabasal cells had MUC4 staining, and 48.5% had an intensity of 2 or 3. All samples with immature squamous metaplasia were positive through the entire epithelial thickness. Cervical intraepithelial neoplasia (CIN) 1 samples had variable staining with an intensity similar to glycogenated squamous epithelium but distribution similar to squamous metaplasia. All CIN 3 (n=21) and invasive squamous cell carcinomas (n=17) had increased MUC4 staining intensity (P<0.001 and P<0.001) and increased diffuse staining (P<0.001 and P<0.001) compared with the limited staining in glycogenated squamous epithelium. In contrast, no differences in staining were observed between benign endocervical glands, adenocarcinoma in situ, and invasive adenocarcinoma. These expression patterns suggest that MUC4 is a lineage marker in benign cervical tissue that may have aberrant expression in squamous dysplasia and carcinoma. Further studies may elucidate the role of MUC4 in the development of squamous cell cervical cancer.
authors.affiliation: Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Munro
authors.forename: Maneesh
authors.initials: M
authors.lastname: Jain
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Neel
authors.initials: N
authors.lastname: Kamal
authors.forename: Subodh M
authors.initials: SM
authors.lastname: Lele
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Lynch
authors.forename: Lankai
authors.initials: L
authors.lastname: Guo
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.forename: Poonam
authors.initials: P
authors.lastname: Sharma
authors.forename: Steve
authors.initials: S
authors.lastname: Remmenga
authors.forename: Whitfield B
authors.initials: WB
authors.lastname: Growdon
authors.forename: John S
authors.initials: JS
authors.lastname: Davis
authors.forename: Bo R
authors.initials: BR
authors.lastname: Rueda
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055264:Mucin-4 / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C524658:MUC4 protein, human; D055264:Mucin-4