Expression of Cytokeratins 17 and 5 Identifies a Group of Breast Carcinomas with Poor Clinical Outcome

Abstract

While several prognostic factors have been identified in breast carcinoma, the clinical outcome remains hard to predict for individual patients. Better predictive markers are needed to help guide difficult treatment decisions. In a previous study of 78 breast carcinoma specimens, we noted an association between poor clinical outcome and the expression of cytokeratin 17 and/or cytokeratin 5 mRNAs. Here we describe the results of immunohistochemistry studies using monoclonal antibodies against these markers to analyze more than 600 paraffin-embedded breast tumors in tissue microarrays. We found that expression of cytokeratin 17 and/or cytokeratin 5/6 in tumor cells was associated with a poor clinical outcome. Moreover, multivariate analysis showed that in node-negative breast carcinoma, expression of these cytokeratins was a prognostic factor independent of tumor size and tumor grade.

The proteins FABP7 and OATP2 are associated with the basal phenotype and patient outcome in human breast cancer

“…In conclusion, the study has demonstrated the biological, pathological and clinical features of FABP7 and OATP2 protein expression in human breast carcinoma and with respect to FABP7 particularly its relationship and significance in BP breast cancer [12,13,15,18,22,23,25,28,43,54]. These novel biomarkers have significant associations, both independently and within the BP, on tumour behaviour, expression of other biomarkers, and clinical outcome.…”

“…The basal-like type or BP of breast cancer has been subject to extensive investigation in recent years, mainly due to its association with poor patient survival [13,15,22,23,43,44]. Despite this interest, there is currently no robust definition for designation of "basal-like" or BP breast cancer in routine clinical practice, furthermore tumours with a BP are also now recognised to exhibit heterogeneity [14,23].…”

“…Furthermore the expression of basal CKs in breast cancer and their association with poor prognosis has confirmed by several studies [8][9][10][11]. However, basal-like class of tumours have recently received much attention after their identification in gene expression profiling (GEP) studies as a molecularly distinct subtype of breast cancer Although patients with basal-like tumours are generally characterised by shorter disease free survival, high mortality rate and experience a unique pattern of distant metastasis [12,13], it must be noted that this is not always the case, as some authors have reported a heterogeneity within basal like tumours and other studies have failed to show an association with poorer outcome [14][15][16]. Identification of the basal subset can be achieved by GEP or an immunophenotype (IHC).…”

“…Most IHC based definitions use positive expression of basal CKs as the basis to define the basal group [12,13,15,[25][26][27] as additional markers have so far failed to refine further the identification of poor survival cases.. Other authors argue that basal CKs are not always expressed by the basal-like group of tumours identified by gene analyses, and hence novel markers must be incorporated into its definition [28].…”

Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma

“…In total, there were 23 normal livers and 120 malignant hepatocellular carcinomas, among other control tissues. Tissue arrays were constructed as previously described, 16,17 with core sizes ranging from 0.6 to 2 mm on different arrays. Arrays were scored using a four-tier scale: 0-negative (no staining), 1-equivocal, 2-weak positive (weak to moderate intensity in any percentage of tumor cells), and 3-strong positive (strong intensity in at least 50% of tumor cells).…”