title: Immunolocalization of BRCA1 protein in tumor breast tissue: prescreening of BRCA1 mutation in Tunisian patients with hereditary breast cancer?
abstract: BRCA1 is a tumor suppressor gene which is inactivated by mutation in familial breast and ovarian cancers. Over 300 different disease causing germ-line mutations have been described; 60% are unique to an individual family. This diversity and the large size of the gene lead us to search for a prescreening method for BRCA1 mutations. Since BRCA1 is a nuclear protein in normal cells, but reported by some authors to be cytoplasmic in breast tumor cells of patients with BRCA1 mutation, we evaluated immunohistochemistry as a prescreening technique to identify BRCA1 mutations in patients with familial presentation of breast cancer. Using a monoclonal antibody against the carboxy-terminal region of BRCA1, we performed immunohistochemistry on 18 tumor samples from patients with hereditary breast cancer. Cytoplasmic staining of BRCA1 was observed in 10 cases. Of the 18 tumors, 12 (66%) showed either BRCA mutation or BRCA1 accumulation or both, indicating that BRCA1 function might be lost in breast tumor cells not only through mutation, but also via abnormal cytoplasmic location. The immunohistochemical test used in this study would not be efficient as a pre-screening method of deleterious mutations, but it appeared useful to investigate tumor physiology.
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology at Faculty of Sciences of Tunis, Faculty of Sciences of Tunis, Campus Universitaire El Manar I 1060 Tunis, Tunisia. Wafa_t@yahoo.com
authors.forename: Wafa
authors.initials: W
authors.lastname: Troudi
authors.forename: N
authors.initials: N
authors.lastname: Uhrhammer
authors.forename: K
authors.initials: K
authors.lastname: Ben Romdhane
authors.forename: C
authors.initials: C
authors.lastname: Sibille
authors.forename: W
authors.initials: W
authors.lastname: Mahfoudh
authors.forename: L
authors.initials: L
authors.lastname: Chouchane
authors.forename: F
authors.initials: F
authors.lastname: Ben Ayed
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Bignon
authors.forename: A
authors.initials: A
authors.lastname: Ben Ammar Elgaaied
mesh_terms: D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010375:Pedigree; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014416:Tunisia / Q000453:epidemiology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53