Skip to main content
. 2016 Apr 20;2016(4):CD012165. doi: 10.1002/14651858.CD012165
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