title: Characterization of RhoC expression in benign and malignant breast disease: a potential new marker for small breast carcinomas with metastatic ability.
abstract: The most important factor in predicting outcome in patients with early breast cancer is the stage of the disease. There is no robust marker capable of identifying invasive carcinomas that despite their small size have a high metastatic potential, and that would benefit from more aggressive treatment. RhoC-GTPase is a member of the Ras-superfamily and is involved in cell polarity and motility. We hypothesized that RhoC expression would be a good marker to identify breast cancer patients with high risk of developing metastases, and that it would be a prognostic marker useful in the clinic. We developed a specific anti-RhoC antibody and studied archival breast tissues that comprise a broad spectrum of breast disease. One hundred eighty-two specimens from 164 patients were used. Immunohistochemistry was performed on formalin-fixed tissues. Staining intensity was graded 0 to 3+ (0 to 1+ was considered negative and 2 to 3+ was considered positive). RhoC was not expressed in any of the normal, fibrocystic changes, atypical hyperplasia, or ductal carcinoma in situ, but was expressed in 36 of 118 invasive carcinomas and strongly correlated with tumor stage (P = 0.01). RhoC had high specificity (88%) in detecting invasive carcinomas with metastatic potential. Of the invasive carcinomas smaller than 1 cm, RhoC was highly specific in detecting tumors that developed metastases. RhoC expression was associated with negative progesterone receptor and HER-2/neu overexpression. We characterized RhoC expression in human breast tissues. RhoC is specifically expressed in invasive breast carcinomas capable of metastasizing, and it may be clinically useful in patients with tumors smaller than 1 cm to guide treatment.
authors.affiliation: Department of Pathology, Division of Hematology and Oncology, 2G332 University Hospital, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0054, USA. kleer@umich.edu
authors.forename: Celina G
authors.initials: CG
authors.lastname: Kleer
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: van Golen
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhi-Fen
authors.initials: ZF
authors.lastname: Wu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Sofia D
authors.initials: SD
authors.lastname: Merajver
mesh_terms: D000818:Animals; D000906:Antibodies; D014408:Biomarkers, Tumor; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005348:Fibrocystic Breast Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein; C066690:RHOC protein, human; C512911:Rhoc protein, mouse