High Concordance Between Herceptest Immunohistochemistry and ERBB2 Fluorescence in Situ Hybridization Before and After Implementation of American Society of Clinical Oncology/College of American Pathology 2007 Guidelines

Maria E Vergara-Lluri; Neda A Moatamed; Elizabeth Hong; Sophia K Apple

Disclosures

Mod Pathol. 2012;25(10):1326-1332. 

In This Article

Results

Concordance Rates

Overall, our concordance rate between non-equivocal HER2 immunohistochemical analysis and ERBB2 fluorescence in-situ hybridization results was 97.6%. Thirty of 1269 (2.4%) non-equivocal total cases displayed immunohistochemical scores discordant with fluorescence in-situ hybridization results, ie, 27 cases had negative immunohistochemical scores but positive (amplified) fluorescence in-situ hybridization results (false negative), while 3 cases had positive immunohistochemical scores with negative (non-amplified) fluorescence in-situ hybridization results (false positive).

For the 2003–2007 study population, the concordance between the HER2 immunohistochemical analysis and ERBB2 fluorescence in-situ hybridization assays was 97.6% with a k of 0.90, corresponding to near perfect agreement ( Table 4 ). The equivocal immunohistochemical 2+ cases were excluded from analysis (n=121; 12% of cases). For the 2008–2010 study population, the concordance between the two assays was 97.6% with a k of 0.89 ( Table 4 ). The equivocal immunohistochemical 2+ cases were excluded from analysis (n=47; 11% of cases). Thus, the k between cases scored in 2003–2007 vs 2008–2011, k=0.90 vs k=0.89, were essentially similar. This was reflected in the identical concordance rates of 97.6% between cases scored in 2003–2007 vs 2008–2010.

Changes in Percentages of Inconclusive/Equivocal and Positive Cases

Overall, cases with inconclusive immunohistochemical score of 2+ comprised 168 of the total 1437 (11.7%). The percentage of inconclusive/equivocal cases was 12% (121/1016 cases) using US FDA guidelines and was 11% (47/421 cases) using ASCO/CAP guidelines. A χ 2-test demonstrated no significant decline in inconclusive/equivocal cases (P=0.64).

Overall, cases with positive HER2 immunohistochemical score of 3+ comprised 162 of the total 1437 (11.3%). The percentage of positive cases by immunohistochemistry decreased from 12% (118/1016) to 10% (44/421) after implementation of ASCO/CAP guidelines, albeit not reaching statistical significance (P=0.46). However, a change in the scoring of ERBB2 fluorescence in-situ hybridization cases resulted in a decrease of ERBB2-amplified cases from 19% (191/1016) to 15% (62/421), which is significant (P=0.03) ( Table 5 ).

Discordant Results and Comparison Between US FDA Guidelines and ASCO/CAP Guidelines

Overall, when fluorescence in-situ hybridization result was considered as the gold standard, the false-negative rate was 27 cases of 1437 (1.9%), ie, cases which were negative on immunohistochemistry and positive (amplified) on fluorescence in-situ hybridization analysis (5 cases scored immunohistochemically as 0; 22 cases scored immunohistochemically as 1+) in our entire study population from 2003–2010. The false-positive rate was 3 cases of 1437 (0.2%); three cases were positive on immunohistochemistry (3+) yet proved to be negative (non-amplified) by fluorescence in-situ hybridization analysis.

US FDA Guidelines (2003–2007) Of 1016 total cases, the false-negative rate was 2.1% (n=21) and the false-positive rate was 0% ( Table 4 ).

ASCO/CAP Guidelines (2008–2010) Of 421 total cases, the false-negative rate was 1.4% (n=6) and false-positive rate was 0.7% (n=3) ( Table 4 ).

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