title: Expression of B7-H1 in breast cancer patients is strongly associated with high proliferative Ki-67-expressing tumor cells.
abstract: B7-H1, a co-inhibitory molecule, plays a role in immune escape of tumors. We have shown previously the expression of this molecule in breast cancer patients and demonstrated its association with high histological grade, progesterone and estrogen receptor negative status, all of which are known to have direct impact on cell proliferation. In the present work, we investigated the effect of proliferation, as measured by Ki-67 and mitotic count, on the induction of B7-H1. We used H&E stained sections to score for mitotic count in 69 breast cancer patients. Immunohistochemistry was used to investigate B7-H1 and Ki-67 expression. The relationship between B7-H1 induction and cell proliferation was further investigated in primary cultured cells. B7-H1 expression was recorded in patients with a high mitotic index (p = 0.007). There was a high significant correlation between B7-H1 expression and the presence of the proliferative marker Ki-67 (p < 0.001) indicating the association of proliferation with B7-H1 induction. Furthermore, B7-H1 was gradually induced in proliferating cells of 8/8 primary cell lines as measured by Ki-67 expression. Finally, B7-H1 was downregulated in quiescent cells and upregulated in cells stimulated with a mitogen confirming the association of proliferation with the induction of B7-H1. We have shown for the first time a direct association between proliferation and the expression of B7-H1 in breast cancer patients. The relationship between B7-H1 induction and cell proliferation was also thoroughly investigated in vitro, in which a strong link between B7-H1 expression and the presence of the proliferative Ki-67 marker was clearly demonstrated.
authors.affiliation: Tumor Immunology Unit, Department Biological and Medical Research, King Faisal Specialist Hospital and Research Center, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. SDERMIME@KFSHRC.EDU.SA
authors.forename: Hazem
authors.initials: H
authors.lastname: Ghebeh
authors.forename: Asma
authors.initials: A
authors.lastname: Tulbah
authors.forename: Shamayel
authors.initials: S
authors.lastname: Mohammed
authors.forename: Naser
authors.initials: N
authors.lastname: Elkum
authors.forename: Suad M
authors.initials: SM
authors.lastname: Bin Amer
authors.forename: Taher
authors.initials: T
authors.lastname: Al-Tweigeri
authors.forename: Said
authors.initials: S
authors.lastname: Dermime
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D060890:B7-H1 Antigen; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008940:Mitotic Index; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016192:Resting Phase, Cell Cycle
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone