Table 1.
Prognostic biomarkers for cancer medicine.
| Prognostic biomarker | Type of cancer | Clinical significance | Detection | Clinical use | References |
|---|---|---|---|---|---|
| Beta-tubulin | NSCLC | High expression of beta-tubulin confers worse prognosis | IHC | No | [Seve et al. 2007; Winton et al. 2005] |
| BRCA1 | Breast | High expression of BRCA1 confers worse prognosis in untreated patients | IHC | Yes | [James et al. 2007] |
| NSCLC | High expression of BRCA1 confers worse prognosis in untreated patients | qRT-PCR | No | [Rosell et al. 2007] | |
| CA19-9 | Pancreatic | Higher preoperative CA19-9 levels are associated with lower resectability, more advanced stage and inferior survival | IHC | No | [Ferrone et al. 2006] |
| CAIX | RCC | High expression of CAIX is associated with a better prognosis | IHC | No | [Bui et al. 2003] |
| CD44 | Bladder | Expression of CD44 is associated with poor prognosis | qRT-PCR | No | [Miyake et al. 2002] |
| CEA | CRC | Elevated preoperative CEA levels in resectable colorectal cancer is associated with poor prognosis | IHC | Yes | [Wolmark et al. 1984; Wanebo et al. 1978] |
| c-KIT | GIST | GIST patients have a better prognosis if they harbor a mutation in exon 11 of the c-KIT gene | Pathway detection via FDG-PET | Yes | [Singer et al. 2002] |
| ColoPrint | CRC | Prognosis for colorectal cancer patients | Microarray | Yes | [Glas et al. 2009] |
| CTC (e.g. CellSearch) | Melanoma | Increased number of circulating melanoma cells is associated with poor prognosis | Circulating tumor cells | No | [Nezos et al. 2009] |
| CRC | Colorectal patients with ≥3 CTC/7.5 ml of peripheral blood were associated with shorter PFS and OS, i.e. poor prognosis | Circulating tumor cells | Yes | [Cohen et al. 2009] | |
| Breast | Breast cancer patients with ≥5 CTC/7.5 ml of peripheral blood are associated with shorter PFS and OS, i.e. poor prognosis | Circulating tumor cells | Yes | [Cristofanilli et al. 2004] | |
| Prostate | ≥5 CTC/7.5 ml of peripheral blood is associated with poor prognosis | Circulating tumor cells | Yes | [Cristofanilli et al. 2004] | |
| Cyclin D1 | Bladder | Expression of Cyclin D1 is associated with low grade, low stage and recurrence | IHC | No | [Liukkonen et al. 2000] |
| Cyclin E | Bladder | Expression of Cyclin E is associated with low stage and survival | IHC | No | [Richter et al. 2000] |
| E-Cadherin | Bladder | E-Cadherin is associated with poor prognosis | IHC | No | [Bringuier et al. 1993] |
| EGFR | Bladder | Overexpression of EGFR is associated with high grade and high stage | IHC | No | [Nguyen et al. 1994] |
| NSCLC | High gene copy number of EGFR in NSCLC patients is associated with poor prognosis | FISH / SA | No | [Coate et al. 2009] | |
| NSCLC | EGFR mutation in NSCLC patients is associated with better prognosis in untreated patients | ||||
| Rectal | Overexpression of EGFR in rectal cancers is also associated with poor prognosis | IHC | No | [Kuremsky et al. 2009] | |
| ER | Breast | Patients with ER-positive breast tumors have better survival than patients with hormonal negative tumors | IHC | Yes | [Early Breast Cancer Trialists’ Collaborative Group, 1998] |
| eXageneBC | Breast | Provides prognosis in node-positive or node-negative breast cancer patients | FISH | Yes | [Davis et al. 2007] |
| Her2/neu | Breast | Patients with Her2/neu-positive breast tumors are more aggressive and have a worse prognosis compared to Her2/neu-negative tumors | FISH | Yes | [Mass et al. 2005] |
| Bladder | Overexpression of Her2/neu is associated with high grade, high stage, poor survival and metastasis in bladder cancer | IHC | No | [Lipponen et al. 1991] | |
| GIST | Overexpression of Her2/neu in advanced gastric cancer patients is associated with poor prognosis | IHC | No | [Scartozzi et al. 2009] | |
| Her3 | Melanoma | Correlation with increased cell proliferation, tumor progression and reduced survival in melanoma patients | IHC | No | [Reschke et al. 2008] |
| ING3 | Melanoma | Reduced nuclear expression associated with poor disease-specific survival in melanoma patients | IHC | No | [Wang et al. 2007] |
| ING4 | Melanoma | Reduced levels of ING4 in melanoma patients is associated with melanoma thickness, ulceration and poor disease-specific survival and overall survival | IHC | No | [Li et al. 2008] |
| Ki-67 | Bladder | Expression of Ki-67 is associated with progression and recurrence in bladder cancer | IHC | No | [Gerdes et al. 1984] |
| Breast | Expression of Ki-67 is associated with proliferation and progression in breast cancer | IHC | No | [Dowsett et al. 2007] | |
| K-ras | NSCLC | K-ras mutation is associated with poor prognosis in NSCLC patients | SA | Yes | [Zhu et al. 2008] |
| LOH at 18q | CRC | Associated with metastasis and poor prognosis in colorectal tumors | PCR | No | [Watanabe et al. 2001] |
| MammaPrint | Breast | A 70-gene prognostic assay used to identify breast cancer cases at the extreme end of the spectrum of disease outcome by identifying patients with good or very poor prognosis | Microarray | Yes | [Van ‘t Veer et al. 2002] |
| Mammostrat® | Breast | This standard purely prognostic test uses five antibodies with manual slide scoring to divide cases of ER-positive, lymph node negative breast cancer tumors treated with tamoxifen alone into low-, moderate- or high-risk groups | IHC | Yes | [Ring et al. 2006] |
| MMP-2 | Bladder | Expression of MMP-2 is associated with poor prognosis in bladder cancer patients | PCR | No | [Xu et al. 2002] |
| MSI status | CRC | High frequency MSI colorectal tumors are associated with better prognosis and show improved relapse-free survival | IHC | No | [Kim et al. 2007] |
| NCOA3 | Melanoma | Increased levels in melanoma patients correspond to poor relapse-free survival and disease-free survival | IHC | No | [Rangel et al. 2006] |
| Oncotype DX | Breast | A 21-gene multiplex test used for prognosis to determine 10-year disease recurrence for ER-positive, lymph node negative breast cancers using a continuous variable algorithm and assigning a tripartite recurrence score | qRT-PCR | Yes | [Goldstein et al. 2008; Paik et al. 2004] |
| p21 | Bladder | Overexpression of p21 is associated with poor prognosis | IHC | No | [Stein et al. 1998] |
| p53 | Bladder | Overexpression of p53 is associated with poor prognosis | IHC | No | [Schmitz-Drager et al. 2000] |
| NSCLC | High expression of p53 in NSCLC patients confers worse prognosis in untreated patients | IHC | No | [Tsao et al. 2007] | |
| NSCLC | TP53 mutation in NSCLC patients is associated with worse prognosis | SA | No | ||
| PR | Breast | Patients with PR-positive breast tumors have better survival than patients with hormonal-negative tumors | IHC | Yes | [Dowsett et al. 2006] |
| Rb | Bladder | Overexpression of Rb is associated with poor prognosis | IHC | No | [Logothetis et al. 1992] |
| RRMI | NSCLC | High expression of RRMI in NSCLC patients confers better prognosis in untreated patients | AQUA | No | [Zheng et al. 2007] |
| VEGF | RCC | Overexpression of VEGF is associated with poor prognosis in clear cell renal carcinoma patients | IHC | Yes | [Oldenhuis et al. 2008] |
AQUA, automated quantitative analysis; CA19-9, carbohydrate antigen 19-9; CAIX, carbonic anhydrase IX; CEA, carcinoembryonic antigen; CRC, colorectal tumor; CTC, circulating tumor cells; EGFR, epidermal growth factor receptor; ER, estrogen receptor; FDG, 18F-fluorodeoxyglucose; FISH, fluorescent in situ hybridization; GIST, gastrointestinal stromal tumor; IHC, immunohistochemistry; LOH, loss of heterozygosity; MMP-2, matrix metalloproteinase-2; MSI, microsatellite instability; NSCLC, non-small cell lung cancer; OS, overall survival; PET, Positron emission tomography; PFS, progression-free survival; PR, progesterone receptor; qRT-PCR, quantitative real time polymerase chain reaction; Rb, retinoblastoma; RCC, renal cell carcinoma; RRMI, ribonucleotide reductase messenger 1; SA, sequence analysis; VEGF, vascular endothelial growth factor.