title: Stromal CD10 expression in invasive breast carcinoma correlates with poor prognosis, estrogen receptor negativity, and high grade.
abstract: CD10 is a zinc-dependent peptidase (metalloproteinase), which degrades a variety of bioactive peptides. Earlier studies suggested that CD10 expression in tumor stroma is associated with biological aggressiveness of the tumor. To date, only one study has addressed the clinical significance of stromal CD10 expression in invasive carcinoma of the breast. The aim of this confirmatory study is to evaluate stromal CD10 expression in breast carcinoma and to examine associations between CD10, clinicopathological variables, and patient outcome. Tissue microarrays, containing 438 cases of invasive breast carcinoma and 15 cases of ductal carcinoma in situ with 15 years median follow-up time, were assembled. CD10 expression was assessed by immunohistochemistry and scored as negative, weak and strong. Nonparametric correlational tests, univariate and multivariate survival analyses were performed. Stromal CD10 was preferentially expressed in invasive compared to noninvasive breast cancers (P=0.003). There were correlations between stromal CD10 expression and higher tumor grade (P=0.01) and estrogen receptor (ER) negative status (P=0.002). There was no correlation between CD10 and lymph node status, tumor size, histological subtype, progesterone receptors, and Her2 status. Stromal CD 10 expression was associated with decreased long-term disease-specific and overall survival in the entire cohort (P<0.01), and in lymph node negative (P<0.05), but not lymph node positive subset of patients. It approached prognostic significance in multivariate analysis (P=0.06) when lymph node status, tumor size, ER and Her2 were considered in the same model; and was associated with a relative risk of death of 2.8, compared to relative risk of 2.4 for lymph node positive status. Thus, stromal CD10 expression in invasive carcinoma of the breast is associated with ER negativity, higher tumor grade and decreased survival and constitutes a potential prognostic marker and a target for development of novel therapies.
authors.affiliation: Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre of Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada. nmakrets@yahoo.com
authors.forename: Nikita A
authors.initials: NA
authors.lastname: Makretsov
authors.forename: Malcolm
authors.initials: M
authors.lastname: Hayes
authors.forename: Beverley A
authors.initials: BA
authors.lastname: Carter
authors.forename: Shahriar
authors.initials: S
authors.lastname: Dabiri
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D005109:Extracellular Matrix / Q000276:immunology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D015260:Neprilysin / Q000032:analysis*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology*; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D015260:Neprilysin