title: Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125).
abstract: Mucins are being implicated in diagnosis, prognosis, and as therapeutic targets due to their aberrant expression in a variety of carcinomas. Here, we have analyzed the expression of MUC4 and have compared its potential usefulness in early detection and prognosis of ovarian carcinoma alone and in combination with other mucin antigens, MUC1 and MUC16. Clinical significance of the differential mucin expression was evaluated by grouping the tumor samples in early (stage I and II) and advanced (stage III and IV) stage cases and histological subtypes (serous, mucinous, endometrioid and clear cell). Correlation of these mucins with patient's survival (n=63) was determined by Kaplan-Meier analysis in order to predict their prognostic value. MUC4 showed significant overexpression in tumor cases (P<0.0001) with highest incidence (92.0%) among all three mucins. A significant overexpression of MUC1 (P<0.018) and MUC16 (P<0.0001) was also observed in 83.0 and 79.0% of tumor samples, respectively. Notably, MUC4 expression was significantly higher (P</=0.004) compared to both MUC1 and MUC16 in early-stage ovarian tumor samples with 100% incidence. In advanced stage ovarian tumors, all the mucins displayed overall comparable expression, nonetheless, MUC4 had highest prevalence (88.0%) compared to MUC1 (84.0%) and MUC16 (81.0%). A combined panel of MUC4 with MUC16 detected 100% of the late-stage tumor cases without compromising the specificity. Among histological subtypes, only MUC4 displayed 100% (n=5) sensitivity in mucinous ovarian tumors, while MUC1 and MUC16 detected 40 and 20% cases, respectively. The expression of MUC4, however, did not significantly correlate with the survival of the ovarian cancer patient, while a significant correlation of MUC16 with poor prognosis was observed. In conclusion, our study demonstrates that MUC4 could be a potential candidate marker for early diagnosis of epithelial ovarian carcinoma and can be utilized in combination with MUC16 to achieve greater sensitivity for the detection of late-stage tumors.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
authors.forename: Ajay P
authors.initials: AP
authors.lastname: Singh
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ruiz
authors.forename: Sonny L
authors.initials: SL
authors.lastname: Johansson
authors.forename: Maneesh
authors.initials: M
authors.lastname: Jain
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Smith
authors.forename: Nicolas
authors.initials: N
authors.lastname: Moniaux
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000737:chemistry* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000737:chemistry* / Q000473:pathology; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018394:CA-125 Antigen / Q000032:analysis*; D018269:Carcinoma, Endometrioid / Q000737:chemistry* / Q000473:pathology; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis*; D018396:Mucin-1; D055264:Mucin-4; D009077:Mucins / Q000032:analysis*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C060192:MUC1 protein, human; C451759:MUC16 protein, human; C524658:MUC4 protein, human; D008565:Membrane Proteins; D018396:Mucin-1; D055264:Mucin-4; D009077:Mucins