title: Spread of endometriosis to pelvic sentinel lymph nodes: gene expression analysis.
abstract: OBJECTIVE
  Endometriotic spread to the lymphatic system has been described, but little is known about the molecular events and changes in gene expression associated with this process. We sought to determine the expression levels of a panel of 28 genes in samples of primary endometriosis lesions (EL), isolated endometriotic-like cells (IELC)-positive pelvic sentinel lymph nodes (PSLN), and IELC-negative PSLN, in order to identify candidate genes that may play a role in this process.
  
  
  METHODS
  Quantitative real-time PCR and immunohistochemistry (IHC) of primary EL and PSLN samples with and without IELC from patients with ovarian and/or peritoneal endometriosis.
  
  
  RESULTS
  Gene expression was analyzed in EL (n=13), IELC-positive PSLN (PSLN+, n=11), and IELC-negative PSLN (PSLN-, n=8). Gene expression differences between PSLN+ and PSLN- were analyzed and evaluated in relation to their expression levels in EL. Genes expressed at high levels in EL but not in PSLN- and known to be expressed in IELC (such as ESR1, PGR) served as controls and the expected gene dilution effect was clearly observed. Expression of a set of genes (CXCR4, CD68, MKI67, and CD44) was found to be higher in PSLN+ vs. PSLN-, while lowest in EL, indicating upregulation in IELC. In contrast, EPCAM and E-cadherin, which were strongly expressed in EL, were not found to be expressed in PSLN+, and thus likely absent from IELC. IHC confirmed the expression of CXCR4, CD44s, and CD44v6 in IELC, as well as the absence of E-cadherin from IELC.
  
  
  CONCLUSIONS
  Our data indicate that spread of endometriosis to PSLN is accompanied by differential expression of several genes, including EPCAM, CDH1 (E-cadherin), CXCR4, and CD44, suggesting an involvement of CD44 splice variants as well as CXCR4 signalling in this process.
authors: Department of Obstetrics and Gynaecology, Ruhr-Universität Bochum, Marienhospital Herne, Düngelstrasse 33, Herne, Germany.
authors: Bernd
authors: B
authors: Bürkle
authors: Nadine K
authors: NK
authors: Notscheid
authors: Jan
authors: J
authors: Scheich
authors: Lukas
authors: L
authors: Hefler
authors: Clemens B
authors: CB
authors: Tempfer
authors: Reinhard
authors: R
authors: Horvat
authors: Günther A
authors: GA
authors: Rezniczek
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D010388:Pelvis; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015820:Cadherins; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen; D019718:Receptors, CXCR4; C497483:CD44 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C527276:CXCR4 protein, human
keywords: Endometriosis; Gene expression; Metastasis; Sentinel lymph node