Q & A
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September 2011 Editor: Q. Oncologists have been requesting HER2/neu testing on gastric and gas-tro-esophageal carcinomas. Are the testing parameters different from those for breast cancer? A. The Food and Drug Administration recently approved trastuzumab (Herceptin) for treatment of metastatic gastric and gastroesophageal junction adenocarcinoma (G-GE), based on data from an international phase three randomized study of Trastuzumab for GAstric Cancer, or ToGA,1 demonstrating a 2.7-month survival benefit of trastuzumab (Herceptin) plus chemotherapy in HER2+ advanced G-GE adenocarcinoma, as compared with chemotherapy alone.
The FDA approved Dako’s HER2 IHC and FISH assays for use in gastric cancer testing concurrently with its approval of trastuzumab for treatment of advanced gastric cancer. European data demonstrated excellent concordance using two different HER2 IHC kits, and two FISH kits, as well as other brightfield in situ hybridization methods.4 At present, HER2 assays for gastric carcinoma should be validated as appropriate for predictive markers (see CAP checklist ANP.22969 and ANP.22970); further guidelines may be forthcoming. A CAP Survey for HER2 immunohistochemistry in G-GE carcinoma will be available soon (GHER2) specifically for G-GE carcinoma. Further details and illustrations can be found in the references. References
Megan L. Troxell, MD, PhD Q. Every newborn in the United States is checked for metabolic diseases through a comprehensive newborn screening system. Why then is there a need to do alternative tests for reducing substances in the urine specimens of young children? A. Detection of reducing substances in urine is a laboratory procedure that has been used for decades because it is easy to perform, results can be reported rapidly, and, historically, it was an early method of detecting serious inborn errors of metabolism. The reducing substance assay involves adding a reagent tablet to urine for detection of reducing substances (glucose and other carbohydrate metabolites), using the classic Benedict’s copper reduction reaction. If the reducing test is positive and the enzymatic dipstick assay for urinary glucose is negative, the presence of substances other than glucose is suggested. A positive test requires additional urine and blood testing and clinical evaluation to diagnose the actual inborn error of metabolism. Some hospitals, especially pediatric facilities, perform a urine reducing substance assay on all children under age 5 whenever a urinalysis is ordered. Many states began performing blood tandem mass spectrometry (MS/MS) as early as 1998 as a part of their newborn screening panels. Tandem mass spectrometry is an excellent method for detecting numerous inborn errors of metabolism. Now nearly all states follow the American College of Medical Genetics’ recommendation to screen for 29 metabolic disorders and perform tandem mass spectrometry on newborns. With the success of newborn screening, the question is raised whether it is still necessary to perform urine tests for reducing substances on all children.1 In some pediatric hospitals, the urine reducing substance assay is now performed only when the clinician orders it and not as a routine part of urinalysis. In the case of a sick newborn in whom the newborn screening results are not yet available, the urine reducing substance assay may be useful; the rapid result could help support a diagnosis of an inborn error of metabolism such as fructosemia or galactosemia. Because there are no current national recommendations on the performance of urine reducing substance assays, each laboratory should review its patient population and determine the best utility and ordering options for this assay. Reference
Deborah A. Perry, MD Dr. Kiechle is medical director of clinical pathology, Memorial Healthcare, Hollywood, Fla. |
An accompanying study investigated HER2 testing parameters, and proposed modified HER2 scoring schema for G-GE carcinoma (Table 1).1-4 Analysis of the ToGA pathologic material showed that strong basolateral HER2 membrane staining by immunohistochemistry (IHC) correlates with HER2 amplification by fluorescence in situ hybridization (FISH); additionally, G-GE carcinoma has a greater tendency toward HER2 heterogeneity as compared with breast carcinoma (~five percent heterogeneous G-GE cases1). These data have been incorporated into the consensus recommendations for G-GE HER2 scoring (Table 1), which differ from breast cancer scoring. In G-GE carcinoma, basolateral (incomplete) membrane staining is scored, and circumferential staining is not required. For biopsy specimens, amplification or strong basolateral staining in a small cluster of cells is reported as positive, while the 10 percent threshold is maintained for resection specimens. 
percent) of HER2 FISH-amplified but IHC-negative cases (0, 1+) (ToGA trial1) as compared with breast carcinoma. A ToGA subgroup analysis found that HER2 FISH-amplified but IHC-negative (0, 1+) cases derive little benefit from trastuzumab, while the survival benefit excluding these cases was longer, at 4.2 months.1 On the other hand, a subgroup analysis of heterogeneously HER2- positive cases has not been published.