Affiliations of authors: Breast and Gynaecological Cancer Laboratory (JP); Human Genetics Department (EH, AO, JB); Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Department of Pathology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain (CR); Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (OD).
Correspondence to: José Palacios, MD, Breast and Gynaecological Cancer Laboratory, Molecular Pathology Programme, Centro Nacional Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro, 3, 28029 Madrid, Spain (e-mail: jpalacios{at}cnio.es)
Several reports have established that sporadic breast carcinomas with expression of basal cell (myoepithelial cell) markers, such as P-cadherin and high molecular weight cytokeratins CK5/6, CK14, and CK17, show specific morphologic and prognostic characteristics (1,2). In cDNA studies, Perou et al. (3) also defined a subgroup of estrogen receptor (ER)-negative/HER2-negative breast cancers characterized by the expression of the basal cell markers. Recently, Sorlie et al. (4) reanalyzed cDNA microarray data from vant Veer et al. (5) and observed that most carcinomas with a BRCA1 mutation had the gene expression profile of basal type cells. In a recent issue of this Journal, Foulkes et al. (6) reported that the expression of CK5/6 was statistically significantly associated with ER-negative/HER2-negative BRCA1-related cancers (15 [88%] of 17 tumors), when compared with ER-negative/HER2-negative sporadic cancers (25 [45%] of 55 tumors) in Askenazi Jewish women younger than 65 years. In addition, we have recently reported that the expression of P-cadherin is also most common in BRCA1-related cancers than in familial BRCA2-related and non-BRCA1/2- related cancers (7).
To further test the hypothesis that the basal cell phenotype is BRCA1-related, we analyzed the basal cytokeratin CK5/6 and the ductal cytokeratin CK8 in infiltrating ductal carcinomas (IDCs) from 20 patients with a BRCA1 mutation (mean age = 42 years) and 14 patients with a BRCA2 mutation (mean age = 42.6 years) genes. The morphological and some immunohistochemical features of this series have been recently published (7). In addition, 59 patients with non-familial IDCs (mean age = 42.6 years) were studied, as an age-matched control group. All tumors were included in a tissue microarray and subjected to immunohistochemistry as previously described (7). Positive CK5/6 expression was as reported by Foulkes et al. (6). Reduced expression of CK8 was recorded when less than 50% of tumor cells expressed this marker.
In our series, CK5/6 was expressed in nine (45%) of 20 BRCA1-related carcinomas, one (7%) of 14 BRCA2-related carcinomas, and five (8%) of 59 sporadic breast carcinomas, respectively (P<.001) (Fig. 1). The ER-negative/HER2-negative phenotype was present in 15 (75%), one (7%), and eight (14%) of the BRCA1-related, BRCA2-related, and sporadic breast cancers, respectively (P<.001). The complete ER-negative/HER2-negative and CK5/6-positive phenotype was observed in nine (45%), one (7%), and three (5%) BRCA1-related, BRCA2-related, and sporadic breast carcinomas, respectively (P<.001). When we considered only cases with an ER-negative/HER2-negative phenotype, CK5/6 was expressed in nine (60%) of 15 BRCA1-related carcinomas and three (37%) of eight sporadic breast carcinomas, although this difference was not statistically significant, in contrast to the results of Foulkes et al. (6). The smaller number of case patients and the different ethnic population analyzed in our study may explain the discrepancies between series. In this sense, most case patients in the study of Foulkes et al. (6) were probably related to the BRCA1 Ashkenazi Jewish founder mutations, which could be associated with a more homogeneous breast cancer phenotype. In any case, the present study supports the existence of a subtype of high-grade, ER-negative/HER2-negative breast carcinomas with a basal phenotype that occurs more frequently in BRCA1-related than in sporadic carcinomas. This phenotype can also occur, although very infrequently, in BRCA2-related breast cancer.
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REFERENCES
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2 van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 2002;161:19916.
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