Basal cytokeratins in breast tumours among BRCA1, BRCA2 and mutation-negative breast cancer families.
BACKGROUND
Finding new immunohistochemical markers that are specific to hereditary breast cancer could help us to select candidates for BRCA1/BRCA2 mutation testing and to understand the biological pathways of tumour development.


METHODS
Using breast cancer tumour microarrays, immunohistochemical expression of cytokeratin (CK)-5/6, CK-14 and CK-17 was evaluated in breast tumours from BRCA1 families (n = 46), BRCA2 families (n = 40), non-BRCA1/BRCA2 families (n = 358) and familial breast cancer patients with one first-degree relative affected by breast or ovarian cancer (n = 270), as well as from patients with sporadic breast cancer (n = 364). Staining for CK-5/6, CK-14 and CK-17 was compared between these groups and correlated with other clinical and histological factors.


RESULTS
CK-5/6, CK-14 and CK-17 were detected mostly among oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative and high-grade tumours. We found the highest percentages of samples positive for these CKs among ER-negative/HER2-negative tumours. In univariate analysis, CK-14 was significantly associated with tumours from BRCA1 (39%; P < 0.0005), BRCA2 (27%; P = 0.011), and non-BRCA1/BRCA2 (21%; P < 0.005) families, as compared with sporadic tumours (10%). However, in multivariate analysis, CKs were not found to be independently associated with BRCA1 or BRCA2 mutation status, and the most effective predictors of BRCA1 mutations were age at onset, HER2 status, and either ER or PR status.


CONCLUSIONS
Although our study confirms that basal CKs can help to identify BRCA1 mutation carriers, this effect was weaker than previously suggested and CKs did not independently predict BRCA1 mutation either from sporadic or familial breast cancer cases. The most effective, independent predictors of BRCA1 mutations were age at onset, HER2 status, and either ER or PR status, as compared with sporadic or non-BRCA1/BRCA2 cancers.
Eerola
Hannaleena
H
Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu, 00029 HUS, Helsinki Finland. hannaleena.eerola@fimnet.fi
Heinonen
Mira
M
Heikkilä
Päivi
P
Kilpivaara
Outi
O
Tamminen
Anitta
A
Aittomäki
Kristiina
K
Blomqvist
Carl
C
Ristimäki
Ari
A
Nevanlinna
Heli
H
D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000032:analysis; D053537:Keratin-17 / Q000032:analysis; D053555:Keratin-5 / Q000032:analysis; D053553:Keratin-6 / Q000032:analysis; D007633:Keratins / Q000032:analysis*; D008875:Middle Aged; D009154:Mutation
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D053547:Keratin-14; D053537:Keratin-17; D053555:Keratin-5; D053553:Keratin-6; D007633:Keratins