Comparison of histopathological and gene expression-based typing of cancer of unknown primary

Abstract

For the clinical diagnosis and appropriate therapy of patients with cancer of unknown primary (CUP), biopsies of the tumor metastases are generally examined histopathologically and by immunohistochemistry (IHC). Gene expression profiling (GEP) is a new diagnostic technique that might further contribute to tumor specification. Biopsies of 43 CUP cases underwent a retrospective central histopathological and immunohistochemical review and centrally performed GEP using CupPrint(TM). Two samples could not be evaluated by IHC due to small biopsy size or loss of immunoreactivity. One of these and 17 other samples were not suited for GEP due to RNA degradation. In 13 out of the remaining 24 cases (54%), the same primary was proposed by IHC and GEP and was supported by the clinical findings, furthermore leading to the doubtless identification of the primary in four out of these. In seven cases, there was discordance between IHC and GEP, with the clinical picture being more in line with IHC in three and with GEP in four cases. Four cases had to remain undecided because the primary tumors suggested by IHC and GEP were not supported. In conclusion, overlap between IHC and GEP results and the clinical presentation was noted in the majority of those true CUP cases that were evaluable with both techniques. Therefore, GEP can be a complementary diagnostic technique assisting immunohistochemical profiling of cancer biopsies with unknown primary.

Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Site

“…19 Regardless of disease classification, an important discussion has recently emerged surrounding the need to locate the primary tumor site when a patient presents with metastatic disease. The cost of a complete diagnostic workup for CUP-including multimodality diagnostic imaging procedures, [20][21][22][23] tissue IHC panels, [24][25][26] serum tumor marker panels, 27,28 and mRNA profiling 28-32 -commonly exceeds $10 000. For 25% or more of these patients, after a thorough workup, the primary site will remain unknown, and no therapies will be considered "on label.…”

Risk factors for cancers of unknown primary site: Results from the prospective EPIC cohort

“…Treatment of CUP is guided by the suspected origin of the primary tumor, and therefore extensive diagnostic work‐up is generally applied in order to identify the tissue‐of‐origin. In spite of many new methods that have been introduced for the characterization of CUP, including immunohistochemical and gene expression profiling and advanced imaging techniques, the primary tumor still often evades identification, probably because the primary tumor remains dormant or has disappeared. Our analyses provide further documentation, in addition to autopsy studies, that a substantial proportion of cancers of unknown primary site may have their origin in smoking‐related tumors, in particular.…”

Imaging mass spectrometry to discriminate breast from pancreatic cancer metastasis in formalin‐fixed paraffin‐embedded tissues

“…These techniques are complicated by the fact that metastases are moderately or poorly differentiated and have lost specific features of the primary tumor. To solve this problem several molecular techniques that classify metastases, such as in situ hybridization, PCR‐based detection of mutations, microRNA‐technology or gene expression profiling techniques , have emerged during the last few years. However, these methods are time‐consuming, labor‐intensive, expensive, and have relied only on a limited set of tumor features, or genetic variations.…”