Review question | Which endometrial biomarkers are unlikely to serve as a basis for a diagnostic test for endometriosis? | ||||
Importance | Biomarkers that did not show differential expression in women with and without endometriosis are unlikely to be helpful in a diagnostic sense and hence are not worth pursuing. These findings are based on adequately designed studies that met inclusion criteria for this review. | ||||
Patients | Reproductive‐aged women with suspected endometriosis or persistent ovarian mass, or women undergoing infertility work‐up | ||||
Settings | Hospitals (public or private of any level), outpatient clinics (general gynaecology, reproductive medicine, pelvic pain) or radiology departments | ||||
Reference standard | Visualisation of endometriosis at surgery (laparoscopy or laparotomy) with or without histological confirmation | ||||
Study design | Cross‐sectional, single gate design (N = 11) or two‐gate design (N = 18); unable to determine if single‐ or two‐gate design for 2 studies. Prospective enrolment; a study could assess more than 1 test or more than 1 type of endometriosis | ||||
Risk of bias | Overall judgement | Poor quality (no studies had 'low risk' assessment in all 4 domains) | |||
Patient selection bias | High risk: 29 studies; unclear risk: 2 studies; low risk: 0 studies | ||||
Index test interpretation bias | High risk: 28 studies; unclear risk: 3 studies; low risk: 0 studies | ||||
Reference standard interpretation bias | High risk: 0 studies; unclear risk: 13 studies; low risk: 18 studies | ||||
Flow and timing selection bias | High risk: 12 studies; unclear risk: 2 studies; low risk: 17 studies | ||||
Applicability concerns | Concerns regarding patient selection | High concern ‐ 25 studies; unclear concern ‐ 3 studies; low concern ‐ 3 studies | |||
Concerns regarding index test | High concern ‐ 0 studies; unclear concern ‐ 0 studies; low concern ‐ 31 studies | ||||
Concerns regarding reference standard | High concern ‐ 0 studies; unclear concern ‐ 0 studies; low concern ‐ 31 studies | ||||
Biomarker | Expression levels |
rASRM stage |
Menstrual cycle phase |
Sample collection method |
Reference |
1. Angiogenesis and growth factors and their receptors | |||||
EGF mRNA (epidermal growth factor) | Endometriosis (N = 35)a: 0.13 ± 0.01 Controls (N = 31): 0.24 ± 0.02; P = 0.120 # sub‐analysis per cycle phase ‐ similar findings |
III‐IV | Proliferative/secretory | 'Endometrial curettage' ‐ likely sharp | Lee 2007 |
FGF‐2 mRNA (fibroblast growth factor‐2) | Endometriosis (N = 35)a: 17.38 ± 1.73 Controls (N = 31): 20.0 ± 2.53; P = 0.572 # sub‐analysis per cycle phase ‐ similar findings |
III‐IV | Proliferative/secretory | 'Endometrial curettage' ‐ likely sharp | Lee 2007 |
Glycodelin mRNA (PP14 or PAEP) (placental protein 14 or progestogen‐associated endometrial protein) | Endometriosis (N = 17)a: 2.5 (0.6‐4.5) Controls (N = 10): 0.936 (0.1‐1.9); P = NS | II‐IV | Proliferative | Sharp curettage | Meola 2009 |
PDGF‐A mRNA (platelet‐derived growth factor A) | Endometriosis (N = 35)a: 6.52 ± 0.58 Controls (N = 31): 13.02 ± 1.60; P = 0.572 # sub‐analysis per cycle phase ‐ similar findings |
III‐IV | Proliferative/secretory | 'Endometrial curettage' ‐ likely sharp | Lee 2007 |
PIGF (placental growth factor) | Endometriosis (N = 18)a: 120 ± 31 Controls (N = 23): 87 ± 16; P = NS Endometriosis (N = 22)a: 87 ± 30 Controls (N = 27): 109 ± 15; P = NS |
III‐IV | Proliferative Secretory |
Aspiration curettage | Gilabert‐Estelles 2007 |
PIGF mRNA (placental growth factor) | Endometriosis (N = 18)a: 0.050 ± 0.017 Controls (N = 23): 0.032 ± 0.009 Endometriosis (N = 22)a: 0.037 ± 0.016 Controls (N = 27): 0.024 ± 0.004; P = NS |
III‐IV | Proliferative Secretory |
Aspiration curettage | Gilabert‐Estelles 2007 |
PKR1 mRNA (prokineticin receptor 1), EG‐VEGF receptor | Endometriosis (N = 9)b: 1.89 (0.1–5.5) Controls (N = 14): 3.92 (0.0–23.4); P = NS Endometriosis (N = 6)b: 0.43 (0–2.1) Controls (N = 19): 0.64 (0.0–6.7); P = NS |
— | Proliferative Secretory |
Aspiration curettage | Lee 2010 |
PKR2 mRNA (prokineticin receptor 2), EG‐VEGF receptor | Endometriosis (N = 9)b: 0.93 (0.0–10.7) Controls (N = 14): 0.75 (0.0–6.6); P = NS Endometriosis (N = 6)b: 0.24 (0.0–1.2) Controls (N = 19): 0 (0.0–1.0); P = NS |
— | Proliferative Secretory |
Aspiration curettage | Lee 2010 |
TSP‐1 (thrombospondin‐1) | Endometriosis (N = 18)a: 313 ± 46 ng/mg Controls (N = 23): 210 ± 27 ng/mg; P = NS Endometriosis (N = 22)a: 413 ± 63 ng/mg Controls (N = 27): 317 ± 42 ng/mg; P = NS |
III‐IV | Proliferative Secretory |
Aspiration curettage | Gilabert‐Estelles 2007 |
TSP‐1 (thrombospondin‐1) | Endometriosis (N = 58)a: 140 ± 28 ng/mg Controls (N = 38): 81 ± 16 ng/mg; P = NS Endometriosis (N = 58)a: 69 ± 16 ng/mg Controls (N = 38): 69 ± 13 ng/mg; P = NS |
— | Proliferative Secretory |
Aspiration curettage | Ramon 2011 |
TSP‐1 mRNA (thrombospondin‐1) | Endometriosis (N = 18)a: 2.621 ± 0.735 Controls (N = 23): 1.510 ± 0.270; P = NS Endometriosis (N = 22)a: 3.093 ± 0.7002 Controls (N = 27): 2.370 ± 0.910; P = NS |
III‐IV | Proliferative Secretory |
Aspiration curettage | Gilabert‐Estelles 2007 |
TSP‐1 mRNA (thrombospondin‐1) | Endometriosis (N = 58)a: 1.79 ± 0.36 Controls (N = 38): 2.36 ± 0.49; P = NS Endometriosis (N = 58)a: 2.65 ± 0.87 Controls (N = 38): 1.52 ± 0.39; P = NS |
— | Proliferative Secretory |
Aspiration curettage | Ramon 2011 |
TYMP (thymidine phosphorylase) | Endometriosis (N = 15)b: 11.8 (2.7–38.6) ng/ml Controls (N = 14): 16.8 (1.1–37.6) ng/ml; P = 0.68 |
III‐IV | Proliferative | Aspiration curettage | Laudanski 2014 |
VEGF (vascular endothelial growth factor) | Endometriosis (N = 10)b: 0.142 (0.087‐0.943) Controls (N = 7): 0.129 (0.097‐0.837); P = 0.943 |
II‐IV | Menstrual | Menstrual fluid | Da Silva 2014 |
VEGF mRNA (vascular endothelial growth factor) | Endometriosis (N = 24)b: 5.83 (2.5‐8.75) Controls (N = 23): 5.01 (1.7‐10.83); P = NS # sub‐analysis per cycle phase ‐ similar findings |
III‐IV | Proliferative/secretory | 'Endometrial biopsy curette' ‐ not specified | Cho 2012 |
EG‐VEGF mRNA (endocrine gland‐derived VEGF) | Endometriosis (N = 9)b: 0.04 (2.9 × 10‐4– 0.6) Controls (N = 14): 0.03 (5.2 × 10‐6–1.0); P = NS Endometriosis (N = 6)b: 0.28 (2.0 × 10‐4–5.6) Controls (N = 19): 1.50 (0.0–27.9); P = NS |
— | Proliferative Secretory |
Aspiration curettage | Lee 2010 |
VEGF/sFlt (VEGF and soluble fms‐like tyrosine kinase ratio) | Endometriosis (N = 24)b: 1.06 (0.71‐2.59) Controls (N = 23): 0.71 (0.35‐1.06); P = 0.064 # sub‐analysis per cycle phase ‐ similar findings |
III‐IV | Proliferative/secretory | 'Endometrial biopsy curette' ‐ not specified | Cho 2012 |
2. Apoptosis markers and regulators | |||||
Bax mRNA (BCL2‐associated X protein) | Endometriosis (15)b: 1.22 Controls (N = 30): 1.15; P = NS |
I‐IV | Proliferative | Sharp curettage | Zubor 2009 |
Bcl‐xL (B‐cell lymphoma‐extra large, or BCL2‐like‐1 isoform 1) | Endometriosis (15)b: 1.08 Controls (N = 30): 1.07; P = NS |
I‐IV | Proliferative | Sharp curettage | Zubor 2009 |
Bcl‐xL:Bcl‐xS ratio (ratio B‐cell lymphoma‐extra large/B‐cell lymphoma‐extra small)E | Endometriosis (15)b: 2.63 Controls (N = 30): 5.63; P = 0.2965 |
I‐IV | Proliferative | Sharp curettage | Zubor 2009 |
3. Cell adhesion molecules and other matrix‐related proteins | |||||
α2β1 integrin | Positively stained menstrual effluent: endometriosis (N = 8)c: 7/8 controls (N = 8): 6/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 8/8 controls (N = 8): 8/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1994 |
α3β1 integrin | Positively stained menstrual effluent: endometriosis (N = 8)c: 7/8 controls (N = 8): 6/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 7/8 controls (N = 8): 7/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1994 |
α4β1 integrin | Positively stained menstrual effluent: endometriosis (N = 8)c: 2/8 controls (N = 8): 3/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 7/8 controls (N = 8): 5/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1994 |
α5β1 integrin | Positively stained menstrual effluent: endometriosis (N = 8)c: 7/8 controls (N = 8): 4/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 8/8 controls (N = 8): 8/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1994 |
α6β1 integrin | Positively stained menstrual effluent: endometriosis (N = 8)c: 2/8 controls (N = 8): 3/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 8/8 controls (N = 8): 8/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1994 |
αVβ3 integrin | Positive samples: endometriosis (N = 20)c: 10 (50) infertile controls (N = 20): 8 (40) fertile controls (N = 20): 7 (35); P = NS endometriosis (N = 16)c: 16 (100) infertile controls (N = 16): 16 (100) fertile controls (N = 19): 18 (94.7); P = NS |
l‐II | Mid‐secretory Late‐secretory |
— | Casals 2012 |
αVβ5 integrins | Glandular cells H Score: endometriosis (N = 40)b: 0.47 (0.0‐1.0) controls (N = 12): 0.6 (0.3‐0.8); P = 0.460 endometriosis (N = 40)b: 1.2 (0.5‐1.9) controls (N = 12): 1.3 (0.9‐1.7); P = 0.507 |
I‐IV | Proliferative Secretory |
— | Puy 2002 |
Stromal cells H Score: endometriosis (N = 40)b: 2.0 (1.0‐2.7) controls (N = 12): 1.9 (1.4‐2.5); P = 0.920 endometriosis (N = 40)b: 1.7 (0.8‐2.7) controls (N = 12): 1.5 (1.1‐2.4); P = 0.752 |
I‐IV | Proliferative Secretory |
— | Puy 2002 | |
αVβ6 integrins | Glandular cells H Score : endometriosis (N = 40)b: 0.5 (0.1‐1.3) controls (N = 12): 0.75 (0.3‐1.2); P = 0.856 endometriosis (N = 40)b: 0.7 (0.3‐0.9) controls (N = 12): 1.0 (0.8‐1.2); P = 0.975 |
I‐IV | Proliferative Secretory |
— | Puy 2002 |
Stromal cells H Score: endometriosis (N = 40)b: 1.4 (0.6‐2.2) controls (N = 12): 1.2 (0.3‐2.5); P = 0.651 endometriosis (N = 40)b: 1.8 (0.8‐2.6) controls (N = 12): 1.7 (1.0‐2.2); P = 0.635 |
I‐IV | Proliferative Secretory |
— | Puy 2002 | |
ICAM1 (intercellular adhesion molecule1) | Endometriosis (N = 8)a: 0.56 ± 0.25 Control (N = 8): 0.69 ± 0.19; P = NS # sub‐analysis per cycle phase ‐ similar findings |
I‐IV | Proliferative/secretory | Aspiration curettage | Pino 2009 |
ICAM1 (CD54) (intercellular adhesion molecule1) | (Small/medium/large cells): endometriosis (N = 10)b: 96 (25–193)/92 (13–106)/106 (18–143) controls (12): 51 (4–453)/48 (5–129)/49 (4–103); P = NS # significant difference between the groups in secretory phase ‐ no data for 2 × 2 table |
— | Proliferative | Aspiration curettage | Prefumo 2002 |
sICAM1 (soluble ICAM1) | Endometriosis (N = 8)a: 0.31 ± 0.16 Control (N = 8): 0.13 ± 0.13; P = NS # sub‐analysis per cycle phase ‐ similar findings |
I‐IV | Proliferative/secretory | Aspiration curettage | Pino 2009 |
ICAM1 mRNA (intercellular adhesion molecule1) | Endometriosis (N = 6)a: 0.44 ± 0.11 Control (N = 6): 0.76 ± 0.11; P = NS |
I‐IV | Proliferative/secretory | Aspiration curettage | Pino 2009 |
E‐cadherin | Positively stained menstrual effluent: endometriosis (N = 8)c: 3/8 controls (N = 8): 3/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 8/8 controls (N = 8): 8/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1994 |
LAMA5 (laminin subunit alpha‐5) | Endometriosis (N = 15)b: 1500 (1060–1840) pg/ml controls (N = 14):1400 (1340–1780) pg/ml; P = 0.95 |
III‐IV | Proliferative | Aspiration curettage | Laudanski 2014 |
LFA‐3 (CD58) (leukocyte function associated molecule‐3) | (Small/medium/large cells): endometriosis (N = 10)b: 101 (64 – 302)/108 (28–155)/65 (35–197) controls (12): 315 (65 – 824)/150 (33–264)/124 (67–164); P = NS endometriosis (N = 10)b: 70 (34–252)/49 (26–184)/48 (37–118) controls (12): 171 (145–643)/134 (94–223)/162 (56–228); P = NS |
— | Proliferative Secretory |
Aspiration curettage | Prefumo 2002 |
MMP‐1 (matrix metalloproteinase‐1) | Endometriosis (N = 8)a: just above detection limit Control (N = 8): just above detection limit; P = NS |
I‐IV | Proliferative/secretory | Aspiration curettage | Pino 2009 |
MMP‐9 (matrix metalloproteinase‐9) | Endometriosis (N = 8)a: 2.75 ± 1.5 Control (N = 8): 0.75 ± 0.13; P = NS # sub‐analysis per cycle phase ‐ similar findings |
I‐IV | Proliferative/secretory | Aspiration curettage | Pino 2009 |
MMP‐9 mRNA (matrix metalloproteinase‐9) | Endometriosis (N = 6)a: 0.21 ± 0.06 Control (N = 6): 0.33 ± 0.07; P = NS |
I‐IV | Proliferative/secretory | Aspiration curettage | Pino 2009 |
OPN (osteopontin) | Positive samples: endometriosis (N = 20)c: 14 (70) infertile controls (N = 20): 13 (65) fertile controls (N = 20): 14 (70); P = NS endometriosis (N = 16)c: 16 (100) infertile controls (N = 16): 16 (100) fertile controls (N = 19): 19 (100); P = NS |
I‐II | Mid‐secretory Late‐secretory |
— | Casals 2012 |
OPN (+)/αVβ3 (+) | Positive samples: endometriosis (N = 20)c: 8 (40) infertile controls (N = 20): 7 (35) fertile controls (N = 20): 6 (30); P = NS endometriosis (N = 16)c: 16 (100) infertile controls (N = 16): 16 (100) fertile controls (N = 19): 18 (94.7); P = NS |
I‐II | Mid‐secretory Late‐secretory |
— | Casals 2012 |
PAI‐1 (plasminogen activator inhibitor ‐ 1) | Antigenic levels: endometriosis (N = 21)a: 0.46 ± 0.18 ng/mg controls (N = 35): 0.73 ± 0.19 ng/mg; P = NS Functional levels: endometriosis (N = 21)a: 1.64 ± 0.59 U/mg controls (N = 35): 1.12 ± 0.35 U/mg; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 |
PAI‐1 (plasminogen activator inhibitor ‐ 1) | Endometriosis (N = 18)a: 1.73 ± 0.56 ng/mg Controls (N = 23): 1.48 ± 0.40 ng/mg Endometriosis (N = 22)a: 2.51 ± 0.65 ng/mg Controls (N = 27): 1.44 ± 0.44 ng/mg; P = NS |
III‐IV | Proliferative Secretory |
Aspiration curettage | Gilabert‐Estelles 2007 |
PAI‐1 mRNA (gene encoding for (plasminogen activator inhibitor ‐ 1) | Endometriosis (N = 18)a: 0.197 ± 0.068 Controls (N = 23): 0.117 ± 0.030 Endometriosis (N = 22)a: 0.496 ± 0.158 Controls (N = 27): 0.131 ± 0.041; P = NS |
III‐IV | Proliferative Secretory |
Aspiration curettage | Gilabert‐Estelles 2007 |
PAI‐2 (plasminogen activator inhibitor ‐ 2) | Antigenic levels: endometriosis (N = 21)a: 10.69 ± 3.33 ng/mg controls (N = 35): 4.53 ± 1.75 ng/mg; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 |
PAI‐3 (plasminogen activator inhibitor ‐ 3) | Antigenic levels: endometriosis (N = 21)a: 233 ± 50 ng/mg controls (N = 35): 340 ± 45 ng/mg; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 |
tPA (tissue‐type plasminogen activator) | Antigenic levels: endometriosis (N = 21)a: 12.69 ± 1.52 ng/mg controls (N = 35): 9.14 ± 1.33 ng/mg; P = NS Functional levels: endometriosis (N = 21)a: 0.41 ± 0.09 U/mg controls (N = 35): 0.58 ± 0.10 U/mg; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 |
uPA (urokinase‐type plasminogen activator) | Functional levels: endometriosis (N = 21)a: 0.11 ± 0.02 ng/mg controls (N = 35): 0.06 ± 0.01 ng/mg; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 |
uPA‐R (urokinase‐type plasminogen activator receptor) | Antigenic levels: endometriosis (N = 21)a: 2.51 ± 0.55 ng/mg controls (N = 35): 2.90 ± 0.32 ng/mg; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 |
tPA‐PAI‐3 (tissue plasminogen activator and plasminogen activator inhibitor ‐ 3 complex) | Antigenic levels: endometriosis (N = 21)a: 0.20 ± 0.10 ng/mg controls (N = 35): 0.06 ± 0.02 ng/mg; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 |
uPA‐PAI‐3 (urokinase plasminogen activator and plasminogen activator inhibitor ‐ 3 complex) | Antigenic levels: endometriosis (N = 21)a: 0.27 ± 0.13 ng/mg controls (N = 35): 0.36 ± 0.18 ng/mg; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 |
TIMP‐1 protein (tissue inhibitor of metalloproteinases‐1) | Endometriosis (N = 45)b: 0.253 ± 0.018 controls (N = 15): 0.267 ± 0.010; P = NS |
II‐IV | Proliferative/secretory | — | Chen 2004 |
Endometriosis (N = 21)a: 31± 6 ng/ml controls (N = 35): 30 ± 5 ng/ml; P = NS |
III‐IV | Menstrual/proliferative/secretory | — | Gilabert‐Estelles 2003 | |
Endometriosis (N = 15)b: 56.7 (13.5–213.5) ng/ml Controls (N = 14): 58 (36.2–187.8) ng/ml; P = 0.45 |
III‐IV | Proliferative | Aspiration curettage | Laudanski 2014 | |
TIMP‐1 mRNA (tissue inhibitor of metalloproteinases‐1) | Endometriosis (N = 18)a: 1.190 ± 0.228 Controls (N = 23): 1.589 ± 0.335 Endometriosis (N = 22)a: 2.028 ± 0.392 Controls (N = 27): 1.506 ± 0.363; P = NS |
III‐IV | Proliferative Secretory |
Aspiration curettage | Gilabert‐Estelles 2007 |
Endometriosis (N = 35)b: 2.31 ± 1.21 Controls (N = 20): 2.40 ± 0.89; P = NS |
I‐IV | Proliferative/secretory | 'Endometrial curettage' ‐ not specified | Li 2006 | |
VCAM‐1 (CD106) (vascular cell adhesion molecule‐1) | (Small/medium/large cells): endometriosis (N = 10)b: 8 (0–42)/3 (2–22)/43 (0–57) controls (12): 34 (0–60)/14 (0–24)/21 (0–64); P = NS endometriosis (N = 10)b: 28 (5–64)/22 (6–60)/18 (10–126) controls (12): 27 (5–130)/18 (3–62)/33 (13–238); P = NS |
— | Proliferative Secretory |
Aspiration curettage | Prefumo 2002 |
4. Cell cycle regulatory molecules | |||||
Cyclin B1 mRNA | Endometriosis (N = 20)b: 0.79 ± 1.08 Controls: (N = 30): 0.51 ± 1.04; P = NS Endometriosis (N = 20)b: 0.98 ± 1.24 Controls (N = 30): 0.50 ± 0.49; P = NS # similar findings were observed for protein expression |
II‐III | Proliferative Secretory |
— | Tang 2009 |
Cdc2 mRNA (cyclin dependent kinase‐2) | Endometriosis (N = 20)b: 5.0 ± 5.0 Controls: (N = 30): 5.0 ± 5.0; P = NS Endometriosis (N = 20)b: 4.5 ± 5.5 Controls (N = 30): 4.5 ± 5.5; P = NS # similar findings were observed for protein expression |
II‐III | Proliferative Secretory |
— | Tang 2009 |
Plk1 mRNA (polo‐like kinase‐1) | Endometriosis (N = 20)b: 1.64 ± 1.18 Controls (N = 30): 1.35 ± 0.91; P = NS Endometriosis (N = 20)b: 0.84 ± 1.04 Controls (N = 30): 0.52 ± 0.44; P = NS # similar findings were observed for protein expression |
II‐III | Proliferative Secretory |
— | Tang 2009 |
5. Cell proliferation markers | |||||
Ki‐67 (Antigen KI‐67 or MKI67, marker of cellular proliferation) | Stromal cells: endometriosis (N = 13)b: 8.4 ± 1.4 controls (N = 6): 10.9 ± 4.8; P = NS endometriosis (N = 12)b: 9.6 ± 1.8 controls (N = 8): 10.5 ± 4.8; P = NS # data for glandular epithelium and blood vessels are also reported ‐ no difference between the groups |
II‐III | Proliferative Secretory |
Sharp curettage | Bourlev 2006 |
BW 495/36, endometrial epithelial marker | Positively stained menstrual effluent: endometriosis (N = 8)c: 8/8 controls (N = 8): 6/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 8/8 controls (N = 8): 7/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1995 |
6. Cytoskeleton molecules | |||||
cytokeratin 18 | Positively stained menstrual effluent: endometriosis (N = 8)c: 8/8 controls (N = 8): 7/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 8/8 controls (N = 8): 8/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1995 |
CK19 or CYFRA 21‐1 (cytokeratin 19) | Positively stained menstrual effluent: endometriosis (N = 8)c: 8/8 controls (N = 8): 7/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 8/8 controls (N = 8): 8/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1995 |
Vimentin | Positively stained menstrual effluent: endometriosis (N = 8)c: 8/8 controls (N = 8): 7/8; P = NS Positively stained endometrium: endometriosis (N = 8)c: 8/8 controls (N = 8): 8/8; P = NS |
I | Early proliferative (day 2‐5) | Aspiration curettage | Van der Linden 1995 |
7. DNA‐repair and telomer maintenance molecules | |||||
Telomerase activity (relative telomerase activity (RTA)) | Endometriosis (N = 30)b: 17.8 ± 30.8 Controls (N = 30): 7.6 ± 13.2; P = NS |
I‐IV | Proliferative/secretory | — | Kim 2007 |
8. High throughput markers | |||||
mRNAome (mRNA microarray) | Endometriosis (N = 31)d: 0 Controls (N = 18): 0 |
I‐IV | Menstrual/secretory | Aspiration curettage | Fassbender 2012 |
9. Hormonal markers | |||||
EST (oestrogen sulphotransferase) | Glandular cells staining: endometriosis (N = 35)e: strong 2, medium 12, weak 8, absent 25 controls (N = 33): strong 9, medium 8, weak 6, absent 10; P = NS Stromal cells staining: endometriosis (N = 35)e: absent 35 controls (N = 33): absent 33; P = NS |
I‐II | Proliferative/secretory | 'Endometrial curettage' ‐ likely sharp | Hudelist 2007 |
LGR7 relaxin receptor mRNA (leucine‐rich G protein‐coupled receptor 7) evaluated to distinguish endometrioma from other non‐malignant ovarian masses |
Endometriosis (N = 4)f: 0.95 Controls (N = 7): 1; P = NS Endometriosis (N = 9)f: 1.27 Controls (N = 12): 1; P = NS |
III‐IV | Proliferative Secretory |
— | Morelli 2010 |
Relaxin mRNA evaluated to distinguish endometrioma from other non‐malignant ovarian masses |
Endometriosis (N = 13)c: 9 (69.2) Control (N = 19): 14 (73.7); P = NS # sub‐analysis per cycle phase ‐ similar findings |
III‐IV | Proliferative/secretory | — | Morelli 2010 |
10. Immune system and inflammatory markers | |||||
A Cytokines | |||||
LIF (leukaemia‐inhibitory factor) | Endometriosis (N = 14)b: 25.53 (12.63–43.32) pg/ml Controls (N = 21): 36.26 (14.45–59.32); P = NS |
I‐II | Secretory | Uterine flushing | Mikolajczyk 2006 |
LIF mRNA (leukaemia‐inhibitory factor gene) | Endometriosis (N = 14)b: 0.90 (0.73–1.09) Controls (N = 21): 0.92 (0.74–1.56); P = NS |
I‐II | Secretory | Aspiration curettage | Mikolajczyk 2006 |
TNF‐a (tumour necrosis factor‐alpha) | Endometriosis (N = 10)b: 386.4 (48.31‐3636.06) Controls (N = 7): 56.02 (10.42‐619.205); P = 0.219 |
II‐IV | Menstrual | Menstrual fluid | Da Silva 2014 |
TNF‐a mRNA (tumour necrosis factor‐alpha) | Endometriosis (N = 25)b: 0.0005 (0.0003–0.0020) Controls (N = 25): 0.0002 (0.0001–0.0007); P = NS |
I‐IV | Proliferative/secretory | 'Endometrial curettage' ‐ not specified | Chen 2013 |
B Immune cells: peripheral blood mononuclear cells (PBMC) | |||||
CD56+ cells (endometrial granulated lymphocytes) | Early/mid/late secretory phase: endometriosis (N = 16)a: 1120 ± 160/1320 ± 160/2200 ± 240 controls (N = 17): 1200 ± 140/1360 ± 200/2440 ± 200; P = NS |
I‐IV | Secretory | — | Klentzeris 1995 |
CD38+ cells (endometrial granulated lymphocytes) | Early/mid/late secretory phase: endometriosis (N = 16)a: 950 ± 200/1650 ± 300/3000 ± 300 controls (N = 17): 1550 ± 300/1750 ± 350/3000 ± 250; P = NS |
I‐IV | Secretory | — | Klentzeris 1995 |
CD22+ cells (B lymphocytes) | early/mid/late secretory phase: endometriosis (N = 16)a: 87 ± 28/92 ± 31/120 ± 24 controls (N = 17): 90±31/104 ± 39/115 ± 28; P = NS |
I‐IV | Secretory | — | Klentzeris 1995 |
CD68+ cells (macrophages) | Endometriosis (N = 31)b: 216.10 ± 104.41 Controls (N = 29): 175.93 ± 43.05; p = 0.06 # sub‐analysis per cycle phase ‐ significant difference between the groups only in proliferative phase ‐ no data for 2 × 2 table |
I‐IV | Any phase | Aspiration curettage | Cetin 2013 |
CD68+ cells (macrophages) | Early/mid/late secretory phase: endometriosis (N = 16)a: 1178 ± 186/1271 ± 287/1643 ± 248 controls (N = 17): 1054 ± 155/1116 ± 155/1519 ± 287; P = NS |
I‐IV | Secretory | — | Klentzeris 1995 |
CD16+ cells (natural killer cells) | Early/mid/late secretory phase: endometriosis (N = 16)a: 1276 ± 377/1305 ± 290/1421 ± 348 controls (N = 17): 957 ± 348/1044 ± 377/1189 ± 290; P = NS |
I‐IV | Secretory | — | Klentzeris 1995 |
CD8+ cells (T suppressor/cytotoxic lymphocytes) | Early/mid/late secretory phase: endometriosis (N = 16)a: 691 ± 109/855 ± 127/891 ± 91 controls (N = 17): 782 ± 73/891 ± 91/964 ± 91; P = NS |
I‐IV | Secretory | — | Klentzeris 1995 |
CD4+ cells (T helper/inducer lymphocytes) | Early/mid/late secretory phase: endometriosis (N = 16)a: 321 ± 57/357 ± 50/400 ± 64 controls (N = 17): 293 ± 57/307 ± 57/343 ± 57; P = NS |
I‐IV | Secretory | — | Klentzeris 1995 |
C Interleukins | |||||
IL‐1β mRNA (interleukin ‐1β) | Endometriosis (N = 25)b: 0.0295 (0.0056–0.1039) Controls (N = 25): 0.008 (0.0040–0.0251); P = NS |
I‐IV | Proliferative/secretory | 'Endometrial curettage' ‐ not specified | Chen 2013 |
IL‐11 (interleukin ‐ 11) | Endometriosis (N = 14)b: not detected Controls (N = 21): not detected; P = NS |
I‐II | Secretory | Uterine flushing | Mikolajczyk 2006 |
IL‐11 mRNA (interleukin ‐ 11) | Endometriosis (N = 14)b: 0.48 (0.39–0.59) Controls (N = 21): 0.52 (0.42–0.61); P = NS |
I‐II | Secretory | Aspiration curettage | Mikolajczyk 2006 |
IL‐1R1 mRNA (interleukin ‐1 receptor type II) | Stroma positive samples: endometriosis (N = 17)c: 9 (53) controls (N = 17): 14 (82); P = 0.299 Glandular cells positive samples: endometriosis (N = 16)c: 13 (81) controls (N = 17): 14 (82); P = 0.411 # sub‐analysis per cycle phase ‐ similar findings |
I‐II | Proliferative/secretory | — | Lawson 2008 |
D other immune/inflammatory markers | |||||
MPO (myeloperoxidase) | Endometriosis (N = 10)b: 1.229 (0.778‐2.094) Controls (N = 7): 1.69 (0.95‐1.84); P = 0.669 |
II‐IV | Menstrual | Menstrual fluid | Da Silva 2014 |
NAG (N‐acetyl‐β‐D‐Glucosaminidase) | Endometriosis (N = 10)b: 723.26 (536.7‐768.73) Controls (N = 7): 663.62 (357.5‐1214.1); P = 1.0 |
II‐IV | Menstrual | Menstrual fluid | Da Silva 2014 |
11. Mediators of prostaglandin biosynthesis | |||||
Akr1B1 mRNA (aldoketoreductase ‐1B1, PGF2a synthase) | Endometriosis (N = 22)b: 216.9 ± 25.9 Controls (N = 12): 217.6 ± 15.6; P = NS Endometriosis (N = 23)b: 121.2 ± 18.7 Controls (N = 17): 188.3 ± 31.9; P = NS |
I‐IV | Proliferative Secretory |
— | Rakhila 2013 |
Akr1C3 mRNA (aldoketoreductase ‐1C3, PGF2a synthase) | Endometriosis (N = 22)b: 132.8 ± 21.1 Controls (N = 12): 127.9 ± 26.5; P = NS Endometriosis (N = 23)b: 185.9 ± 31.1 Controls (N = 17): 196.0 ± 45.9; P = NS |
I‐IV | Proliferative Secretory |
— | Rakhila 2013 |
Cox‐1 mRNA (cyclo‐oxygenase‐1) | Endometriosis (N = 22)b: 263.6 ± 103.1 Controls (N = 12): 237.9 ± 78.3; P = NS Endometriosis (N = 23)b: 1045.0 ± 313.8 Controls (N = 17): 564.6 ± 151.2; P = NS |
I‐IV | Proliferative Secretory |
— | Rakhila 2013 |
15‐PGDH mRNA (15‐hydroxyprostaglandin dehydrogenase) | Endometriosis (N = 22)b: 41.3 ± 11.4 Controls (N = 12): 18.4 ± 3.2; P = NS Endometriosis (N = 23)b: 77.2 ± 51.4 Controls (N = 17): 48.1 ± 26.8; P = NS |
I‐IV | Proliferative Secretory |
— | Rakhila 2013 |
cPGES mRNA (cytosolic PGE2 synthase) | Endometriosis (N = 22)b: 63.6 ± 4.6 Controls (N = 12): 68.3 ± 4.8; P = NS Endometriosis (N = 23)b: 55.2 ± 4.3 Controls (N = 17): 61.4 ± 3.9; P = NS |
I‐IV | Proliferative Secretory |
— | Rakhila 2013 |
12. Nerve sheath and nerve growth markers | |||||
NF (neurofilament) | Endometriosis (N = 20)b: 0.02 ± 0.10 Controls (N = 20): 0.025 ± 1.04; P = NS |
I‐II | Secretory | Aspiration curettage | Bokor 2009 |
NF (neurofilament) | Endometriosis (N = 31): no staining Controls (N = 29): no staining |
I‐IV | Any phase | Aspiration curettage | Cetin 2013 |
PGP 9.5 (protein gene product 9.5) | Endometriosis (N = 31): no staining Controls (N = 29): no staining |
I‐IV | Any phase | Aspiration curettage | Cetin 2013 |
13. Other peptides and proteins | |||||
hBD‐2 mRNA (human b‐defensin‐2) | Endometriosis (N = 25)b: 0.0343 (0.0025–2.0326) Controls (N = 25): 0.0034 (0.0025–0.0424); P = NS |
I‐IV | Proliferative/secretory | 'Endometrial curettage' ‐ not specified | Chen 2013 |
hBD‐2 (human b‐defensin‐2) | Negative samples: endometriosis (N = 25)c: 8 (32) controls (N = 25): 10 (40); P = NS |
I‐IV | Proliferative/secretory | 'Endometrial curettage' ‐ not specified | Chen 2013 |
14. Transcription factors and signalling molecules | |||||
AKT1 (RAC‐alpha serine/threonine‐protein kinase) | Endometriosis (N = 15)b: 7.4 (1.4–15.1) ng/ml Controls (N = 14): 5.6 (1.4–15.4) ng/ml; P = 0.9 |
III‐IV | Proliferative | Aspiration curettage | Laudanski 2014 |
JAG1 (jagged 1 protein) | Endometriosis (N = 15)b: 1.5 (0.3–6.5) ng/ml Controls (N = 14): 1.5 (0.4–2.8) ng/ml; P = 0.82 |
III‐IV | Proliferative | Aspiration curettage | Laudanski 2014 |
NS = Not stated |