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Tissue biomarkers for radiotherapy response identified using IHC |
Marker | Function | Technique | IHC cut point used |
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p53 [22, 23, 25, 27] | Cell cycle checkpoints | IHC | 0 versus 1–4 [22], ≤30% nuclei versus >30% nuclei [23], <20% nuclei versus ≥20% nuclei [25], and 0 versus 1 versus 2–4 [27] |
p16 [28, 29] | Cell cycle checkpoints | IHC | ≤25% versus >25% [28], ≤81.3% versus >81.3% [29] |
Rb1 [28] | Cell cycle checkpoints | IHC | ≤20% versus >20% |
MDM2 [17, 24] | Cell cycle checkpoints | IHC | ≤184 versus >184 AU (IA) [17], ≤3% versus >3% ACIS [24] |
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Ki67 [17–21] | Cell proliferation | IHC | ≤11.3% nuclei versus >11.3% nuclei [17], SI ≤3.5% versus >3.5% [18, 19], continuous and SI ≤7.1% versus >7.1% [20], and SI <6.2% versus ≥6.2% [21] |
PKA [39] | Cell proliferation | IHC | Manual: 0, 1, and 2 versus 3 and 0, 1 versus 2, 3IA: median of 111.8, Q3 of 128.0 and 135.5 |
STAT3 (activated) [40] | Cell proliferation/apoptosis | IHC | Continuous and ACIS ≤29% versus >29% |
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Her2/neu [41] | Growth receptor | IHC | Membrane positivity ≤10% versus >10% |
EGFR [42] | Growth receptor | IHC | Negative versus weak or strong membranous staining |
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Bcl2 [22, 23, 43] | Apoptosis | IHC | Nil versus any cytoplasmic staining [22, 23], ≤20% versus >20% cytoplasmic staining [43] |
Bax [44] | Apoptosis | IHC | Greater or lesser cytoplasm staining intensity relative to normal prostate |
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E-cadherin [15] | Cell adhesion | PCR array, IHC validation | Absent or weak (0/1+) versus moderate or strong (2+/3+) |
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COX2 [32] | Prostaglandin synthesis | IHC | 134 AU (median) and continuous variable [32] |
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LDH5 [37] | Anaerobic metabolism and hypoxia | IHC | <50% cytoplasmic expression and/or <10% nuclear expression versus >50% and >10% |
HIF1a [35, 42] | Hypoxia | IHC | 0% versus <1% versus 1–10% versus 10–33% versus 34–67% versus >67% cytoplasmic staining [35], ≤50% versus >50% nuclear and cytoplasm staining [42] |
VEGF [35, 36] | Hypoxia | IHC | 0% versus <1% versus 1–10% versus 10–50% versus >50% cytoplasmic staining [35], IRS score 0–4 versus 5–8 [36] |
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DNA PKcs [45] | NHEJ | IHC | Nil versus any nuclear staining |
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