Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer.
OBJECTIVE
BRCA1-related breast cancer frequently has a basal epithelial phenotype, and P-cadherin is a basal marker. We undertook a detailed evaluation of the relationship among P-cadherin, prognostic markers in breast cancer, and outcome.


METHODS
This study was restricted to 292 cases of first primary invasive breast cancer diagnosed in Ashkenazi Jewish women between 1980 and 1995. All available blocks were stained for P-cadherin, and 261 were included in the final statistical analyses, including 27 germ line BRCA1 mutation carriers and 8 BRCA2 mutation carriers. Descriptive analyses were done followed by survival analyses and a Poisson regression analysis.


RESULTS
P-cadherin was present in 80 of the 261 breast cancers (31%) and was more frequently present in tumors that have a basal epithelial phenotype [i.e., high-grade, estrogen receptor- and KIP1 (p27(Kip1))-negative tumors, with expression of cytokeratin 5/6, cyclin E, TP53, and presence of BRCA1 mutations and vascular nests (all P < 0.001)]. In a univariate survival model, expression of P-cadherin was associated with a relative risk (RR) of death from breast cancer at a 10-year follow-up of 2.9 (95% confidence interval, 1.8-4.7; P < 0.0001) and was a predictor of poor univariate survival in both lymph node-negative and -positive breast cancers. In a multivariate analysis, the effect of P-cadherin levels was not independent of other basal-related markers. Multivariable interaction modeling showed that P-cadherin positivity was highly predictive of a poor prognosis in small, node-negative breast cancers (RR, 7.1; P = 0.006).


CONCLUSIONS
P-cadherin is a marker for basal-like breast cancers and is strongly associated with the presence of a BRCA1 mutation. It is an adverse prognostic factor, particularly in small, node-negative breast cancers.
Arnes
Jarle B
JB
Department of Pathology, The Gade Institute, Haukeland University Hospital, Bergen, Norway.
Brunet
Jean-Sébastien
JS
Stefansson
Ingunn
I
Bégin
Louis R
LR
Wong
Nora
N
Chappuis
Pierre O
PO
Akslen
Lars A
LA
Foulkes
William D
WD
D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000032:analysis*; D018797:Cell Cycle Proteins / Q000032:analysis; D019927:Cyclin E / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5; D007633:Keratins / Q000032:analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D015820:Cadherins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050760:Cyclin-Dependent Kinase Inhibitor p27; D053555:Keratin-5; D007633:Keratins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C503940:KRT5 protein, human