Cancer diagnostics: The journey from histomorphology to molecular profiling

Abstract

Although histomorphology has made significant advances into the understanding of cancer etiology, classification and pathogenesis, it is sometimes complicated by morphologic ambiguities, and other shortcomings that necessitate the development of ancillary tests to complement its diagnostic value. A new approach to cancer patient management consists of targeting specific molecules or gene mutations in the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic profiling methods are increasingly being developed to identify tumor targeted molecular profile that is the basis of targeted therapy. Novel targeted therapy has revolutionized the treatment of gastrointestinal stromal tumor, renal cell carcinoma and other cancers that were previously difficult to treat with standard chemotherapy. In this review, we discuss the role of histomorphology in cancer diagnosis and management and the rising role of molecular profiling in targeted therapy. Molecular profiling in certain diagnostic and therapeutic difficulties may provide a practical and useful complement to histomorphology and opens new avenues for targeted therapy and alternative methods of cancer patient management.

Keywords: cancer diagnosis; histomorphology; targeted molecular profile; targeted therapy.

Figure 1

Histomorphologic appearance of a retroperitoneal tumor that could not be accurately classified by pathologists despite extensive work-up and opinions of multiple nationally-recognized experts (A. H&E, x100). The tumor responded to treatment with temsirolimus and an immunohistochemical stain revealed immunoreactivity with phosphorylated mTOR antibody test (B. x200).

Figure 2. Triage of clinical specimens to different laboratories in the integrated approach to patient-oriented molecular and histomorphologic diagnosis for targeted real time management