65 vs ≥ 0.65). There were no significant differences in ER mRNA level regardless of the cut-off point selected (p value: 0,752, 0,331, and 0,059, respectively). In the last analysis, when log2 ratio (<0.65 vs ≥ 0.65) cut-off point was selected, only 5 cases were classified as being negative for basal keratin mRNA, whereas remaining 110 cases were classified as being positive. Table 4 Relations between basal keratins expression and ER status assessed by immunohistochemistry
Basal keratin ER p value Negative Positive CK5/6 Negative 20 53 <0,001 Positive 35 7 CK14 Negative 39 59 <0,001 Positive 15 1 CK17 Negative 30 56 <0,001 Positive 25 4 The table contains numbers of patients Table 5 Relationship between ER and basal keratin status assessed by immunohistochemistry Basal
keratin status ER status (number of patients) p value Negative Positive CK5/6 and CK14 and CK17 negative 18 PLX-4720 chemical structure 52 <0,001 CK5/6 or CK14 or CK17 positive 37 8 Discussion Basal-like breast cancers recently have raised a great interest not only regarding clinical differences, but also in relation with new therapeutic possibilities. The vast majority of BRCA1 mutation-related breast tumors represent basal-like subtype. Moreover, Turner et al. have recently reported the high prevalence FDA-approved Drug Library of BRCA1 downregulation in sporadic basal-like breast cancer [15]. There are some promising data that platinum-based chemotherapy may be more effective in patients with BRCA-1 germline mutations or in “”triple-negative”" breast cancer [16, 17]. These observations may emphasize the importance of an easy and simple determination of basal-like phenotype. A microarray analysis is a very elegant and sophisticated method, but for individual genes it is equivalent to estimation of mRNA level by the use of RT-PCR. Both methods have one important weakness — the assessment pentoxifylline of gene expression is based on total mRNA presented in the examined tissue, not only in cancer
cells – and this weakness may produce false results in a proportion of cases. In our study, in a comparison of immunohistochemistry and RT-PCR, regardless of the method of dichotomization and statistical analysis used, there were cases with discordant results. For each cytokeratin, there were cases which were regarded as being positive by one method, and negative by the other one. Fourteen percent of cases were negative for CK5/6 as assessed by an immunohistochemical examination, but presented high CK5 mRNA levels. Similar discordances were also observed for CK14 and CK17. This observation suggests that in some cases high levels of basal keratin mRNA may originate not from cancer cells but possibly also from preexisting normal SU5402 molecular weight myoepithelial cells. Furthermore, due to the post-transcriptional and post-translational mechanisms, the amount of detected mRNA not always directly reflects protein level.
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