Table 1.

Potential sources of endometrial cancer (EC) diagnostic biomarkers, their advantages and disadvantages.

Potential Sources of EC Biomarkers	Description	Advantages	Disadvantages
Blood (serum/plasma)	Blood drawn into sample collection tubes.	Easily accessible Minimally invasive High acceptability to both clinicians and patients.	Challenging matrix for proteomic analysis High protein dynamic range Low cancer derived proteins in early phases of disease. Poor concordance with tissue-derived proteins
Hysterectomy specimens	Tissue specimens obtained following hysterectomy	Viable source of biomarkers Relatively low protein dynamic range Good matrix for proteomic analysis	Highly invasive Low acceptability Not feasible for pre-treatment diagnosis
Pipelle biopsy specimens	Endometrial sampling by insertion of the pipelle into the uterine cavity either blindly or at hysteroscopy	Viable source of biomarkers Minimally invasive Relatively low protein dynamic range Relatively good matrix for proteomics Useful in both symptomatic and asymptomatic women.	Severe pain in up to 25% May miss focal pathologies High risk of insertion failure (22% in nulliparous, 8% in parous) Infection, bleeding, uterine perforation
Uterine lavage	Saline is introduced into the uterine cavity and returned by aspiration.	Viable source of biomarkers Relatively low protein dynamic range Relatively good matrix for proteomics Useful in both symptomatic and asymptomatic women.	Relatively invasive Discomfort and pain Low acceptability especially in asymptomatic women
Pap Smear/cervical scrape	A cervical brush is used to sample the ecto-cervix and the endocervical canal.	Simple and minimally invasive Low cost Widely acceptable Viable source of biomarkers	Discomfort from speculum examination Intimate procedure Less useful in asymptomatic women
Tao Brush biopsy specimens	The Tao brush is inserted into the uterine cavity and used to obtain tissue specimens	Less discomfort than pipelle biopsy Viable source of biomarkers Relatively low protein dynamic range	High cost High risk of insertion failure (20% nulliparous, 8% in parous)
Vaginal tampons/swabs	Vaginal tampons used for 8–12 h	Minimally invasive Potential source of uterine biomarkers in symptomatic women	Unappealing to postmenopausal women Inadequate for EC detection in women without bleeding symptoms
Urine	Usually self-collected	Cheap, simple, non-invasive High level of acceptability Can be collected at home/in privacy Relies on renal excretion of systemic biomarkers or urinary contamination by uterine biomarkers Proteins and peptides are stable in urine and less complex	Biomarkers may not be excreted in urine Urinary contamination by uterine biomarkers may be unreliable especially in asymptomatic or minimally symptomatic women Wide variability in urinary protein concentrations