Molecular Classification of Cancers of Unknown Primary Site
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REVIEW ARTICLE
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Molecular Classification of Cancers of Unknown Primary Site F. Anthony Greco1 and Mark G. Erlander2 1 Sarah Cannon Cancer Center, Nashville, Tennessee, USA 2 bioTheranostics, Inc., San Diego, California, USA
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367 1. Molecular Profiling in Human Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 2. Molecular Profiling in CUP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370 3. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
Abstract
Cancer of unknown primary site is a common metastatic cancer, diagnosed in about 50 000 patients per year in the US. The diagnosis, classification, and management of patients with carcinoma of unknown primary site has been difficult and frustrating. The therapy has usually been empiric for the majority of patients, and their prognosis has been poor. Molecular classification of metastatic cancers with known primary sites has been accurate (76–89%), as reported from several studies. Molecular profiling of initial biopsy specimens has tremendous potential as a test to diagnose the site of tumor origin in patients with unknown primary cancer. Several retrospective studies of molecular profiling assays have provided indirect validation of the accuracy of primary site prediction, based on correlations with clinicopathologic features. One additional study of initial diagnostic biopsies in unknown primary cancer patients, where primary tumor sites were identified months to years later, has provided more direct validation of the accuracy of molecular classification (the primary tumor sites of 15 of 20 patients were correctly predicted). The ability to diagnose and classify unknown primary cancer more precisely would allow for more site-specific or targeted therapy, and likely improve patient outcomes. Several clinical studies are in progress or planned to test this concept.
Cancer of unknown primary site (CUP) is a common metastatic cancer, accounting for about 5% (50 000 patients) of all advanced cancer each year in the US.[1] These patients are unique in that they have no clinically apparent primary cancer to explain the source of their metastasis. CUP is not a single neoplasm with a defined natural history, but a very heterogeneous group with variable clinical features and histopathologies. Diagnosis, classification, and management of these patients has been difficult and frustrating.
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