Table 2.
Local HER2 IHC | Central HER2 IHC | Local HER2 FISH | Local clinical HER2 status | |||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Negative | Equivocal | Positive | Total IHC | Negative | Equivocal | Positive | Total IHC | Non-amplified | Amplified | Total FISH | Negative | Equivocal | Positive | Total HER2 | ||||||||||||||||||
N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % | |||
HERmark | Negative | 69 | 71% | 14 | 14% | 14 | 14% | 97 | 51% | 86 | 86% | 13 | 13% | 1 | 1% | 100 | 52% | 27 | 90% | 3 | 10% | 30 | 45% | 83 | 83% | 1 | 1% | 16 | 16% | 100 | 52% | |
HERmark | Equivocal | 10 | 38% | 9 | 35% | 7 | 27% | 26 | 14% | 17 | 71% | 5 | 21% | 2 | 8% | 24 | 13% | 11 | 92% | 1 | 8% | 12 | 18% | 17 | 65% | 0 | 0% | 9 | 35% | 26 | 13% | |
HERmark | Positive | 9 | 13% | 7 | 10% | 52 | 76% | 68 | 36% | 4 | 6% | 23 | 34% | 41 | 60% | 68 | 35% | 5 | 20% | 20 | 80% | 25 | 37% | 10 | 15% | 0 | 0% | 58 | 85% | 68 | 35% | |
Total | 88 | 46% | 30 | 16% | 73 | 38% | 191 | 100% | 107 | 56% | 41 | 21% | 44 | 23% | 192 | 100% | 43 | 64% | 24 | 36% | 67 | 100% | 110 | 57% | 1 | 1% | 83 | 43% | 194 | 100% | ||
Overall concordance | 68%, (69 + 9 + 52)/191 | 69%, (86 + 5 + 41)/192 | NA# | 73%, (83 + 0 + 58)/194 | ||||||||||||||||||||||||||||
Kappa (CI 95%), overall | 0.475 (0.373 to 0.578); weighted Kappa = 0.545 | 0.481 (0.386 to 0.576); weighted Kappa = 0.631 | 0.510 (0.409 to 0.610); weighted Kappa = 0.583 | |||||||||||||||||||||||||||||
Concordance, excluding Eqv.* | 84%, (69 + 52)/(69 + 9 + 14 + 52) | 96%, (86 + 41)/(86 + 4 + 1 + 41) | 85%, (27 + 20)/(27 + 5 + 3 + 20) | 84%, (83 + 58)/(83 + 10 + 16 + 58) | ||||||||||||||||||||||||||||
Kappa (CI 95%), excluding Eqv. | 0.676 (0.550 to 0.797) | 0.914 (0.841 to 0.988) | 0.705 (0.516 to 0.893) | 0.682 (0.570 to 0.794) |
*Equivocal (Eqv.) cases from both tests were excluded; #NA, overall concordance was not calculated for 2 x 3 table. Central HER2 IHC retesting was performed retrospectively and central HER2 status was defined per ASCO/CAP guidelines for HER2 testing [7]. The results of local HER2 testing were reported by participating study sites based on local IHC and/or local FISH. Percentages may not add up to 100% due to rounding. CI, confidence interval; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry.