Review Article

Genomic and Histopathological Tissue Biomarkers That Predict Radiotherapy Response in Localised Prostate Cancer

Table 1

Predictive tissue biomarkers for radiotherapy response identified using immunohistochemistry (IHC).

Tissue biomarkers for radiotherapy response identified using IHC
MarkerFunctionTechniqueIHC cut point used

p53 [22, 23, 25, 27]Cell cycle checkpointsIHC0 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 checkpointsIHC≤25% versus >25% [28], ≤81.3% versus >81.3% [29]
Rb1 [28]Cell cycle checkpointsIHC≤20% versus >20%
MDM2 [17, 24]Cell cycle checkpointsIHC≤184 versus >184 AU (IA) [17], ≤3% versus >3% ACIS [24]

Ki67 [1721]Cell proliferationIHC≤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 proliferationIHCManual: 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/apoptosisIHCContinuous and ACIS ≤29% versus >29%

Her2/neu [41]Growth receptorIHCMembrane positivity ≤10% versus >10%
EGFR [42]Growth receptorIHCNegative versus weak or strong membranous staining

Bcl2 [22, 23, 43]ApoptosisIHCNil versus any cytoplasmic staining [22, 23], ≤20% versus >20% cytoplasmic staining [43]
Bax [44]ApoptosisIHCGreater or lesser cytoplasm staining intensity relative to normal prostate

E-cadherin [15]Cell adhesionPCR array,
IHC validation
Absent or weak (0/1+) versus moderate or strong (2+/3+)

COX2 [32]Prostaglandin synthesisIHC134 AU (median) and continuous variable [32]

LDH5 [37]Anaerobic metabolism and hypoxiaIHC<50% cytoplasmic expression and/or <10% nuclear expression versus >50% and >10%
HIF1a [35, 42]HypoxiaIHC0% 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]HypoxiaIHC0% versus <1% versus 1–10% versus 10–50% versus >50% cytoplasmic staining [35], IRS score 0–4 versus 5–8 [36]

DNA PKcs [45]NHEJIHCNil versus any nuclear staining

NHEJ: nonhomologous end joining; PCR: polymerase chain reaction; IA: image analysis; IRS: immunoreactive score; AU: arbitrary units; ACIS: automated cellular imaging system; cut point refers to semiquantitative scoring system incorporating staining intensity and percentage of tumour cells positive; SI: staining index.