Table 1.
Summary of PODXL expression profiles in epithelial cancers.
| Types of Carcinoma | PODXL Expression | Diagnostic and Prognostic Significance | References |
|---|---|---|---|
| Breast | Overexpressed in a subset of invasive breast carcinomas (6%), and associated with eightfold increase in relative risks of poor outcome (RR: 8.4). Overexpression is predominantly in higher grade, estrogen and progesterone negative, and lymphatic invasive tumours. | Predictor of cancer progression/poor prognosis. Correlated with increased risk of aggressive phenotype, hormone receptor negativity, and high grade | [15,54] |
| Colorectal | Overexpressed in 5–13% of patients. Associated with increased relative risks of death (HR: 1.98–2.0), reduced 5-year overall survival rates (HR: 1.85–2.28), shorter time to recurrence (HR: 2.11–2.93), and disease-free survival (HR: 2.44). Positive expression is also highly concordant between primary and metastatic lesions. | Predictor of metastatic disease and poor prognosis (in subgroups of left hemi-colon and rectum). | [19,55,56,57] |
| Gastric | Positive expression in 36–75% of patients, correlating with advanced tumour stage and metastasis, poor tumour differentiation, reduced time to recurrence (45% vs. 88%), and disease-specific 5-year survival (24% vs. 43%) as well as overall survival rates (40% vs. 55%). | Predictor of metastatic disease, tumour stage, poor differentiation, and prognosis. | [58,59,60,78] |
| Liver (Hepatocellular carcinoma HCC) | Positive expression in 78% of cases. High expression in sinusoidal endothelia and tumour-like lesions but not in normal adjacent tissues. | Diagnostic marker | [54,61] |
| Lung | |||
| Small cell lung carcinoma | Positive expression in 87% of cases. | Diagnostic marker | [62] |
| Lung adenocarcinoma | Positive expression only in invasive lung adenocarcinomas. | Predictor of aggressive and invasive tumours | [63] |
| Esophageal | Positive expression in 85% of patients, associated with shorter time to recurrence (35% vs. 75%) and 5-year overall survival (28% vs. 69%). | Predictor of poor prognosis | [59] |
| Oral squamous cell | Positive expression in 68% of cases | Diagnostic marker to differentiate oral squamous cell carcinoma from other oral cancers | [64] |
| Ovarian | Overexpressed in 87% of high-grade serous carcinomas. Cell surface expression associated with decreases in disease-free survival (HR: 1.73) | Predictor of poor prognosis in high-grade serous subgroup | [14] |
| Pancreatic ductal adenocarcinoma (PDAC) | Positive expression in 34–44% and overexpressed in 29.4% cases of PDAC cases, associated with high-grade tumours. High expression is associated with poor differentiation, perineural and perivascular invasion, and increased relative risks of death (HR: 1.62–2.21). Overexpression of PODXL in combination with ITGB1 associates with poor postoperative outcomes. |
Predictor of high-grade tumours, aggressive phenotype and poor prognosis | [65,66,67,68,73,79] |
| Periampullary | Positive PODXL expression in 46% of pancreatobillary- type (PB-type) subgroup, associated with female sex and poor differentiation grade. Positive PODXL expression in 18% of intestinal-type (I-type); associated with reduced recurrence free survival (HR: 2.44) and overall survival (HR: 2.32) | Predictor of poor differentiation in PB-type subgroup. Predictor of aggressive phenotype and poor prognosis in I-type subgroup. | [67] |
| Prostate | PODXL germ-line mutation is associated with increased risks of developing aggressive prostate cancer. | Genetic marker | [16] |
| Renal | Overexpressed in a subset of patients (9.6%), associated with reduced rates of metastasis-free survival (HR: 3.59) and disease-specific survival (HR: 7.46). | Predictor of aggressive phenotype, metastatic disease, and poor prognosis | [69] |
| Thyroid | Identified only in undifferentiated thyroid carcinoma (UTC), and positively expressed in 52% of UTC cases. | Diagnostic marker for UTC | [49] |
| Urothelial (bladder) | Positive expression associated with higher-grade tumours, reduced 5-years of overall survival (HR: 2.05–3.28), disease-specific survival (HR: 2.7), and 2-year progression-free survival (HR: 7.16). | Predictor of high-grade tumours and poor prognosis | [70,71] |
| Uterine endometrioid adenocarcinoma (EA) | Positive expression detected in 36% of uterine EA cases and associated with higher tumour grades. | Predictor of high-grade tumours | [72] |