This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laakso, M. Articles by Isola, J. Search for Related Content PubMed PubMed Citation Articles by Laakso, M. Articles by Isola, J.

Basoluminal Carcinoma: A New Biologically and Prognostically Distinct Entity Between Basal and Luminal Breast Cancer

Authors' Affiliations: ¹ Department of Pathology, Seinäjoki Central Hospital, Seinäjoki, Finland; ² Institute of Medical Technology and ³ Department of Oncology, University and University Hospital of Tampere, Tampere, Finland; ⁴ Regional Oncologic Center, Uppsala, Sweden; ⁵ Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland; ⁶ The Norwegian Radium Hospital, Oslo, Norway; ⁷ Department of Oncology, Lund University Hospital, Lund, Sweden; and ⁸ Cancer Centre Karolinska and Radiumhemmet, Karolinska Institute and University Hospital, Stockholm, Sweden

Requests for reprints: Mervi Laakso, Department of Pathology, Seinäjoki Central Hospital, Hanneksenrinne 7, 60220 Seinäjoki, Finland. Phone: 358-6-415-3118; Fax: 358-6-415-4990; E-mail: mervi.laakso{at}epshp.fi.

Purpose: Breast carcinomas expressing basal epithelium cytokeratins constitute a tumor subgroup that is typically hormone receptor negative and shows a distinct gene expression profile. Based on variable basal cytokeratin immunostaining patterns, we hypothesized that the "basal phenotype" tumor group may comprise more than one biological entity.

Experimental Design: Basal cytokeratins 5 and 14 (CK5/14) were stained by immunohistochemistry and the percentage of positive cells was defined by image analysis. The results thus obtained were compared with clinicopathologic characteristics and relapse-free survival.

Results: Of the 506 breast tumors, 53 (10.5%) showed immunoreactivity for CK5/14. Basal cytokeratin expression showed up as two microscopically distinguishable subtypes, i.e., a uniformly positive type ("basal") and a partially positive type ("basoluminal") often displaying a checkerboard-type intratumoral heterogeneity. These subgroups could also be separated with a third basal cytokeratin (CK17, P < 0.0001). Both basal and basoluminal subtypes were hormone receptor negative and of high grade, but differed with respect to the Ki-67 labeling index (P = 0.0014), vimentin (P = 0.005), and c-kit (P = 0.02), which were more frequently expressed in basal than in basoluminal tumors. In contrast, the amplification of HER-2 was found almost exclusively in the basoluminal subgroup (P = 0.009). Compared with the basal tumors, basoluminal tumors associated with significantly shorter relapse-free survival (P = 0.01), which was not explained by their more frequent HER-2 amplification.

Conclusions: We conclude that the intratumoral heterogeneity in basal cytokeratin expression can be used to define two distinct breast cancer subtypes, basal and basoluminal, with distinctive features related to proliferation activity, oncogene and biomarker status, and patient survival.

This article has been cited by other articles:

				H. Sihto, J. Lundin, T. Lehtimaki, M. Sarlomo-Rikala, R. Butzow, K. Holli, L. Sailas, V. Kataja, M. Lundin, T. Turpeenniemi-Hujanen, et al. Molecular Subtypes of Breast Cancers Detected in Mammography Screening and Outside of Screening Clin. Cancer Res., July 1, 2008; 14(13): 4103 - 4110. [Abstract] [Full Text] [PDF]

				E. A. Rakha, J. S. Reis-Filho, and I. O. Ellis Basal-Like Breast Cancer: A Critical Review J. Clin. Oncol., May 20, 2008; 26(15): 2568 - 2581. [Abstract] [Full Text] [PDF]

				E Korsching, S S Jeffrey, W Meinerz, T Decker, W Boecker, and H Buerger Basal carcinoma of the breast revisited: an old entity with new interpretations J. Clin. Pathol., May 1, 2008; 61(5): 553 - 560. [Abstract] [Full Text] [PDF]

				J. Winter Morphological and immunophenotypic analysis of basal-like carcinoma of the breast Bioscience Horizons, March 1, 2008; 1(1): 19 - 27. [Abstract] [Full Text] [PDF]

				L Da Silva, C Clarke, and S R Lakhani Demystifying basal-like breast carcinomas J. Clin. Pathol., December 1, 2007; 60(12): 1328 - 1332. [Abstract] [Full Text] [PDF]

				M. Mimeault and S. K. Batra Interplay of distinct growth factors during epithelial mesenchymal transition of cancer progenitor cells and molecular targeting as novel cancer therapies Ann. Onc., October 1, 2007; 18(10): 1605 - 1619. [Abstract] [Full Text] [PDF]

				D. Razanajaona, S. Joguet, A.-S. Ay, I. Treilleux, S. Goddard-Leon, L. Bartholin, and R. Rimokh Silencing of FLRG, an Antagonist of Activin, Inhibits Human Breast Tumor Cell Growth Cancer Res., August 1, 2007; 67(15): 7223 - 7229. [Abstract] [Full Text] [PDF]