title: BRCA-mutated Invasive Breast Carcinomas: Immunohistochemical Analysis of Insulin-like Growth Factor II mRNA-binding Protein (IMP3), Cytokeratin 8/18, and Cytokeratin 14.
abstract: To evaluate the expression of insulin-like growth factor II mRNA-binding protein (IMP3), CK8/18, and CK14 in BRCA mutated and sporadic invasive breast carcinoma. Immunohistochemistry for IMP3, CK8/18, and CK14 was performed on 39 cases of invasive breast carcinomas with BRCA mutation (24 BRCA1, 14 BRCA2, and 1 dual BRCA1/BRCA2) and 54 cases of sporadic invasive breast carcinomas. The relationship between the IMP3, CK8/18, and CK14 and the tumor grade and molecular phenotypes were analyzed. IMP3, CK8/18, and CK14 positivity were present in 20 (51%), 22 (56%), and 14 (36%) of 39 BRCA-mutated breast carcinomas, and 11 (20%), 53 (98%), and 24 (44%) of 54 sporadic breast carcinomas respectively. The rates of IMP3 expression and absence of CK8/18 (44% versus 2%) in BRCA-mutated breast carcinomas was significantly higher than the sporadic breast carcinomas (p = 0.002 and p < 0.001). No significant difference was observed for CK14 among the two groups (p = 0.408). No significant difference was observed among BRCA1-related and BRCA2-related breast carcinomas in the immunoprofile for IMP3, CK8/18, and CK14. No significant correlation was identified between the expression of IMP3 and CK8/18 and the tumor grade in both BRCA-mutated and sporadic breast carcinomas (p > 0.05). In cases with luminal A and B phenotypes, the rates of expression of IMP3 and loss of CK8/18 were significantly higher in BRCA-mutated as compared to sporadic breast carcinoma (p < 0.001). In cases with basal-like phenotype, the absence of CK8/18 expression was significantly higher in BRCA-mutated breast carcinomas (54% versus 0%, p = 0.001), while no difference was observed for IMP3 expression (p = 0.435). Regardless of mutation type, histologic grade, or molecular phenotype, the absence of CK8/18 expression and presence of IMP3 expression are seen at much higher rate in BRCA mutated breast carcinomas.
authors.affiliation: Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Sambit K
authors.initials: SK
authors.lastname: Mohanty
authors.affiliation: Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Lai
authors.affiliation: Department of Genetics, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Ora K
authors.initials: OK
authors.lastname: Gordon
authors.affiliation: Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Pradhan
authors.affiliation: Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Shikha
authors.initials: S
authors.lastname: Bose
authors.affiliation: Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Dadmanesh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000032:analysis*; D053538:Keratin-18 / Q000032:analysis*; D053533:Keratin-8 / Q000032:analysis*; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000032:analysis*
chemical_list: C498780:IGF2BP3 protein, human; D053547:Keratin-14; D053538:Keratin-18; D053533:Keratin-8; D016601:RNA-Binding Proteins
keywords: BRCA mutation; CK14; CK8/18; IMP3; immunohistochemistry; invasive breast carcinoma