Biotechnology Healthcare - September/October 2008 - (Page 26)

at the same slide and one might call it 2+ positive staining and one might call it 3+ positive staining.” Interpreting a FISH HER2 test, on the other hand, is a much more objective process, FISH proponents argue. With the FISH assay, the pathologist counts actual copies of HER2 genes, which appear as a red “signal” in a blue-stained cancer cell nucleus seen through the microscope. “On a good day, I can count to 20 and I can tell whether there are two copies of a red signal in a blue nucleus or whether there are 20 red signals in a blue nucleus,” says Michael F. Press, MD, PhD, professor of pathology at the Keck School of Medicine, and coordinator of the Women’s Cancers Program at the Norris Comprehensive Cancer Center, University of Southern California. Press and his group at USC, in collaboration with a group led by Dennis J. Slamon, MD, PhD, who led the research for trastuzumab and is now director of the Revlon/ UCLA Women’s Cancer Research Program at Jonsson Comprehensive Cancer Center, in Los Angeles, and chief of the Division of Hematology/ Oncology at UCLA’s Department of Medicine, have amassed more than 20 years of published research on the topic of HER2 testing and the accuracy of IHC and FISH assays. Overall, these studies unambiguously point to FISH as consistently more accurate. In daily practice, however, between 80 and 90 percent of primary HER2 testing in the United States is done with IHC, while only 10 to 20 percent is done with FISH. Approximately 10 percent of IHC test results fall into the so-called “indeterminate” range, and those specimens are re-tested using FISH. If you’re wondering why not just test is more reliable and accurate, so do the FISH test in the first place, we don’t bother with the immunohistochemistry and just do the deyou’re not alone. “That would be my position ex- finitive tests for all the patients,” actly,” says Press, who then goes say Ross. The accuracy of an IHC assay on to suggest several reasons why IHC outnumbers FISH in primary also is more dependent than FISH HER2 testing: Because pathologists on preanalytic variables, such as are familiar with the assay (it’s been how long it takes before the tissue in use since the 1970s); because specimen is fixed, how long it remany pathologists believe that an mains in the fixative solution, and IHC assay is just as accurate as a how it’s subsequently processed. In the United States, the maFISH assay; and because jority of pathology speciit’s fast and relatively inmens are fixed in formalin expensive. Prices vary, but and embedded in paraffin. an IHC assay may cost “In 1989, we showed $100 to $150, and a FISH with molecularly characassay may be double or terized samples that imtriple that price. munohistochemistry has Price certainly is a conthe potential for errosideration, but incorrect “I do not think neously classifying tumors HER2 test results entail far that immunobased on formalin-fixed, greater economic and histochemistry human costs. A 52-week done even in the paraffin-embedded samcourse of chemotherapy best laboratories ples, whereas if one used a plus trastuzumab based on and with the best frozen tissue sample from the same patient, you got a a false positive assay ex- pathologists is relatively accurate result,” ceeds $50,000 and comes good enough,” with a grab bag of nasty says ASCO/CAP says Press. “Formalin fixing and paraffin embedside effects, including po- guideline coauthor Michael F. ding introduce a lot of artential cardiotoxicity. ConPress, MD, PhD, tifacts that confound the versely, a false negative “because the assay results. It’s very hard assay deprives a woman method is to know whether you’re with HER2-positive breast flawed.” getting a good result or a cancer of therapy that can offer a total pathologically complete flawed result.” To be sure, FISH is not without response to treatment (complete disappearance of tumors from both the its disadvantages. Cost again bebreast and lymph nodes) in nearly comes a consideration because FISH requires a fluorescence mihalf of patients. Ross estimates that approxi- croscope, a dark room in which to mately 3 to 4 percent of IHC assays use it, and a board-certified pathin the United States generate a false ologist who can tell the difference negative and are not followed by a between the blue nuclei of cancer FISH test. Of these 3,000 to 4,000 cells in the specimen and the blue women, 1,500 to 2,000 whom oth- nuclei of benign reactive cells. erwise might have benefited from trastuzumab therapy will relapse FLAWED METHOD As painstaking and as wellwith breast cancer. “Labs like mine believe the FISH intentioned as the guideline recom- 26 BIOTECHNOLOGY HEALTHCARE · SEPTEMBER/OCTOBER 2008

Table of Contents Feed for the Digital Edition of Biotechnology Healthcare - September/October 2008

Biotechnology Healthcare - September/October 2008 Openers Editorial/David B. Nash, MD, MBA Contents At a Glance: Multiple Sclerosis Drug Track Personalized Medicine Healthcare Reform’s Effects on Biologic Access Breast Cancer Status Testing: A Crapshoot With Deadly Odds Trends, Issues, and Perspectives In the Management of MS So High-Tech, Yet So Simple The Evolution of Ascertaining the Value Proposition Specialty Pharmacy Employer to Employer Health Plan Confidential Trends

Biotechnology Healthcare - September/October 2008

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