Table 1.
Comparison of mRNA and protein status for ESR1 (ER), PGR (PR), ERBB2 (HER2), and MKI67 (Ki67) determined by IHC and RT-qPCR
| Analyte | IHC+/RTqPCR+ | IHC−/RTqPCR+ | IHC+/RTqPCR− | IHC−/RTqPCR− | Total number | Sensitivity (PPA) (95% CI) | Specificity (NPA) (95% CI) | Kappa statistic (95% CI) | Concordance rate (OPA) (95% CI) |
|---|---|---|---|---|---|---|---|---|---|
| ESR1 (ER)* | 407 | 4 | 7 | 75 | 493 | 98.3% (96.5–99.3%) | 94.9% (87.5–98.6%) | 91.8% (87.1–96.6%) | 97.8% (96.0–98.9%) |
| ESR1 (ER)x | 404 | 7 | 4 | 78 | 493 | 99.0% (97.5–99.7%) | 91.8% (83.8–96.9%) | 92.1% (87.4–96.7%) | 97.8% (96.0–98.9%) |
| PGR (PR)* | 333 | 23 | 23 | 99 | 478 | 93.5% (90.5–95.9%) | 81.1% (73.1–87.7%) | 74.7% (67.8–81.6%) | 90.4% (87.4–92.9%) |
| PGR (PR)x | 320 | 36 | 7 | 115 | 478 | 97.9% (95.6–99.1%) | 76.2% (68.8–82.7%) | 78.1% (71.9–84.2%) | 91.0% (88.1–93.4%) |
| ERBB2 (HER2)** | 66 | 29 | 4 | 391 | 490 | 94.3% (86.0–98.4%) | 93.1% (90.2% − 95.3%) | 76.1% (68.4–83.8%) | 93.3% (90.7–95.3%) |
| ERBB2 (HER2)xx | 42 | 16 | 2 | 361 | 421 | 95.5% (84.5–99.4%) | 95.8% (93.2% − 97.6%) | 80.0% (71.1–88.9%) | 95.7% (90.7–95.3%) |
| ERBB2 (HER2)xxx | 56 | 23 | 6 | 242 | 327 | 90.3% (80.1–96.4%) | 91.3% (87.3% − 94.4%) | 73.9% (65.0–82.8%) | 91.1% (87.5–94.0%) |
| ERBB2 (HER2)*** in ER+ | 39 | 28 | 1 | 341 | 389 | 97.5% (86.8–99.9%) | 92.4% (89.2–94.9%) | 69.1% (58.8–79.5%) | 92.9% (90.0–95.2%) |
| ERBB2 (HER2)**** in ER− | 27 | 1 | 3 | 48 | 79 | 90.0% (73.5–97.9%) | 98.0% (89.1–99.9%) | 89.1% (78.7–99.5%) | 94.9% (87.5–98.6%) |
| MKI67 (Ki67)xxxx | 117 | 63 | 15 | 94 | 289 | 88.6% (82.0%–93.5%) | 59.9% (51.8%–67.6%) | 47.1% (37.6–56.6%) | 73% (67.5–78%) |
| MKi67 (Ki67)xxxxx | 155 | 25 | 37 | 72 | 289 | 80.7% (74.5–85.7%) | 74.2% (64.7–81.9%) | 53.3% (43.2–63.5%) | 78.6% (73.4–82.9%) |
*Using the IHC cut-off of 1% as recommended by ASCO-CAP (2010)
xUsing the IHC cut-off of 10% cut-off, as described elsewhere
**Using central IHC and central FISH for resolution of IHC 2+ to either FISH-negative or FISH-positive, as recommended by the ASCO-CAP guidelines for HER2 testing (2013/2014)
xxComparison of STRAT4 ERBB2 dCt result and HER2 result with IHC 2+ equivocals excluded from analysis using the Herceptest
***In the ER-positive subset only (as determined by IHC), overall percent agreement (OPA), positive percent agreement (PPA), and negative percent agreement (NPA) are shown for the comparison of STRAT4 ERBB2 dCt result and HER2 result by central IHC and central FISH where IHC 2+ equivocals were resolved to positive or negative calls by the FISH assay
xxxComparison of STRAT4 ERBB2 dCt result and HER2 result by central FISH
****In the ER-negative subset only (as determined by IHC), overall percent agreement (OPA), positive percent agreement (PPA), and negative percent agreement (NPA) are shown for the comparison of STRAT4 ERBB2 dCt result and HER2 result by central IHC and central FISH where IHC 2+ equivocals were resolved to positive or negative calls by the FISH assay
xxxxComparison of STRAT4 MKi67 dCt result and Ki67 result by central IHC using a Ki67 IHC cutoff of 20% to discriminate “high proliferation rate” from “low proliferation rate”
xxxxxComparison of STRAT4 MKi67 dCt result and Ki67 result by central IHC using a Ki67 IHC cutoff of 10% to discriminate “high proliferation rate” from “low proliferation rate”