Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary

Abstract

Carcinomas of unknown primary (CUP) represent between 3 and 10% of malignancies. Treatment with nonspecific chemotherapy is commonly unhelpful and the median survival is between 3 and 6 months. Gene expression microarray (GEM) analysis has demonstrated that molecular signatures can aid in tumour classification and propose foster primaries. In this study, we demonstrate the clinical utility of a diagnostic gene expression profiling tool and discuss its potential implications for patient management strategies. Paraffin tumour samples from 21 cases of 'true' CUP patients in whom standard investigation had failed to determine a primary site of malignancy were investigated using diagnostic gene profiling. The results were reviewed in the context of histology and clinical history. Classification of tumour origin using the GEM method confirmed the clinicians' suspicion in 16 out of 21 cases. There was a clinical/ GEM inconsistency in 4 out of 21 patients and a pathological/GEM inconsistency in 1 patient. The improved diagnoses by the GEM method would have influenced the management in 12 out of 21 cases. Genomic profiling and cancer classification tools represent a promising analytical approach to assist with the management of CUP patients. We propose that GEM diagnosis be considered when the primary clinical algorithm has failed to provide a diagnosis.

Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial

“…Specific tumour cell profiles identified by gene expression microarrays may add to establish a working diagnosis in CUP (Ismael et al, 2006;Huebner et al, 2007;Bridgewater et al, 2008;Rosenfeld et al, 2008). The future will show how these techniques can be used to optimise and individualise patient care in CUP.…”

Predicting the site of origin of tumors by a gene expression signature derived from normal tissues

“…Since then, further groups successfully used array-based gene expression profiling to diagnose selected sets of primary cancers and also provided the initial clinical proof of concept through correct prediction of CUP that matched further diagnostic follow-up (Dennis et al, 2002(Dennis et al, , 2005Bloom et al, 2004;Tothill et al, 2005;Ma et al, 2006;Talantov et al, 2006;Dumur et al, 2008;Horlings et al, 2008;Varadhachary et al, 2008;Monzon et al, 2009;van Laar et al, 2009). Today, microarray-based predictors of CUP, such as Agendia's CUPprint, compete with quantitative PCR-based expression profiling or with immunohistochemistry for the best CUP prediction accuracy (Pentheroudakis et al, 2007;Bridgewater et al, 2008;Varadhachary et al, 2008;Monzon et al, 2009;van Laar et al, 2009). However, microarray-based classifiers often have limitations in the numbers, types and subtypes of tumors included in analyses and in low focal prediction accuracy for some tumor types, for example, the low specificity of CUPprint assays for lung and pancreas tumors (Pentheroudakis et al, 2007;Oien and Evans, 2008).…”

Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary

“…9,10 To date, several gene expression-based tests have demonstrated the potential value of this approach in identifying the primary site. 4,[11][12][13][14][15][16][17][18][19][20][21][22][23][24] One microarray-based test uses 2000-GEP to identify a tumour's primary site using formalin-fixed paraffin-embedded (FFPE) specimens (Tissue of Origin test, Response Genetics, Inc., Los Angeles, CA). 24 The test compares the RNA profile of a tumour FFPE specimen to established RNA profiles of 15 known tissues.…”