Section 4 -

Immunohistochemical Classification of Breast Cancer Horst Bürger Gerhard-Domagk-Institute of Pathology University of Muenster Germany

The classification of breast cancer can be done with a multitude of clinical, genetic and pathological approaches. The presence of lymph node metastasis is at the present state of knowledge the most important one. Within the last years a series of studies verified the existence of different subclasses of invasive breast cancer by means of global gene expression analysis. The differential expression patterns of several low and high-molecular weight cytokeratins gave rise to the hypothesis of various breast cancer subgroups with associated prognosis. Interestingly, these expression parameters reflect on one hand tumour grade and established breast cancer subtypes. On the other hand these expression patterns are associated with distinct genetic alterations or alteration patterns. In detail, Sorlie and Perou [1, 2] clearly demonstrated the existence of a subgroup of invasive breast cancer cases, characterised by the expression of basal, high molecular cytokeratins, including Ck 5 [3]. This and previous works were able to demonstrate that these rather rare tumours are associated with an inherited, BRCA1-related background [4, 5] . Further cytogenetic, immunohistochemical analysis of a large series of invasive breast cancer cases could furthermore clearly correlate cytokeratin expression with cytogenetic alteration patterns. Especially the frequencies of chromosomal 16q-losses marked these carcinomas as an own, independent subgroup, rather than the end stage of a dedifferentiation [6, 7]. With the definition of different subgroups of physiological breast cells, including Ck 5 positive progenitor cells, it became obvious that a number of protein expression patterns of these physiological breast cells demonstrate a large overlap with protein expression patterns of distinct breast cancer subgroups [8, 9, 10]. As a consequence of these findings, different cellular compartments might therefore function as different progenitors of invasive breast cancer and its suspected and proposed precursor lesions In consequence the transfer of our knowledge about physiological breast differentiation onto the level of breast carcinogenesis enables a feasible explanation for large heterogeneity of invasive breast cancer, comprising well-differentiated glandular tumours on one end and poorly-differentiated carcinomas on the other end of the morphological and immunohistochemical spectrum. These results are a clear evidence for an important role of cellular subpopulations within the normal breast functioning as cytogenetic pathway specific precursor cells of breast cancer [11, 12] . Whereas a carcinogenic hit of "early-progenitor cells" may cause the evolution of a poorly-differentiated breast cancer, the tumour associated dedifferentiation of a glandular cell seems to be associated with a lower tumour grade. 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