title: Expression of heterochromatin protein 1 in the primary tumor of breast cancer patients in the presence or absence of occult metastatic cells in the bone marrow.
abstract: Gene silencing may occur in breast cancer samples from patients presenting with occult metastatic cells in the bone marrow and one mechanism regulating gene suppression is heterochromatin formation. We have studied whether members of the heterochromatin protein 1 family (HP1Hs alpha, HP1Hs beta and HP1Hs gamma), which take part in chromatin packaging and gene expression regulation, were differentially expressed in tumors from patients with and without occult metastatic cells in their bone marrow. Tumor samples and bone marrow aspirates were obtained from 37 breast cancer patients. Median age was 63 years and 68% of the patients presented with clinical stage I/II disease. Presence of occult metastatic cells in bone marrow was detected through keratin-19 expression by nested RT-PCR in samples from 20 patients (54.1%). The presence of occult metastatic cells in bone marrow was not associated with node involvement, histological grade, estrogen receptor and ERBB2 immunoexpression. Relative gene expression of HP1Hs alpha, HP1Hs beta and HP1Hs gamma was determined by realtime RT-PCR and did not vary according to the presence of occult metastatic cells in bone marrow. In addition, the combined expression of these three transcripts could not be used to classify samples according to the presence of bone marrow micrometastasis. Our work indicates that regulation of heterochromatin formation through HP1 family members may not be the sole mechanism implicated in the metastatic process to the bone marrow.
authors.affiliation: Faculdade de Medicina da Universidade de São Paulo, Departamento de Radiologia, Disciplina de Oncologia, São Paulo and Instituto Brasileiro de Controle do Câncer de São Paulo, São Paulo - Brasil.
authors.forename: A P S
authors.initials: AP
authors.lastname: Abreu
authors.forename: C
authors.initials: C
authors.lastname: Milani
authors.forename: M L H
authors.initials: ML
authors.lastname: Katayama
authors.forename: K C
authors.initials: KC
authors.lastname: Barbosa
authors.forename: L
authors.initials: L
authors.lastname: Gomes da Fonseca
authors.forename: J C S
authors.initials: JC
authors.lastname: Goes
authors.forename: M M
authors.initials: MM
authors.lastname: Brentani
authors.forename: M A A
authors.initials: MA
authors.lastname: Koike Folgueira
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D019046:Bone Marrow Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D020033:Protein Isoforms; D012333:RNA, Messenger; D000090266:Chromobox Protein Homolog 5; D007633:Keratins