title: Lavage of the Uterine Cavity for Molecular Detection of Müllerian Duct Carcinomas: A Proof-of-Concept Study.
abstract: OBJECTIVE
  Type II ovarian cancer (OC) and endometrial cancer (EC) are generally diagnosed at an advanced stage, translating into a poor survival rate. There is increasing evidence that Müllerian duct cancers may exfoliate cells. We have established an approach for lavage of the uterine cavity to detect shed cancer cells.
  
  
  METHODS
  Lavage of the uterine cavity was used to obtain samples from 65 patients, including 30 with OC, five with EC, three with other malignancies, and 27 with benign lesions involving gynecologic organs. These samples, as well as corresponding tumor tissue, were examined for the presence of somatic mutations using massively parallel sequencing (next-generation sequencing) and, in a subset, singleplex analysis.
  
  
  RESULTS
  The lavage technique could be applied successfully, and sufficient amounts of DNA were obtained in all patients. Mutations, mainly in TP53, were identified in 18 (60%) of 30 lavage samples of patients with OC using next-generation sequencing. Singleplex analysis of mutations previously determined in corresponding tumor tissue led to further identification of six patients. Taken together, in 24 (80%) of 30 patients with OC, specific mutations could be identified. This also included one patient with occult OC. All five analyzed lavage specimens from patients with EC harbored mutations. Eight (29.6%) of 27 patients with benign lesions tested positive for mutations, six (75%) as a result of mutations in the KRAS gene.
  
  
  CONCLUSIONS
  This study proved that tumor cells from ovarian neoplasms are shed and can be collected via lavage of the uterine cavity. Detection of OC and EC and even clinically occult OC was achieved, making it a potential tool of significant promise for early diagnosis.
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Maritschnegg
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Pecha
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Els
authors.initials: E
authors.lastname: Van Nieuwenhuysen
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Heitz
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Isaac
authors.initials: I
authors.lastname: Kinde
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany. paul.speiser@meduniwien.ac.at.
authors.forename: Paul
authors.initials: P
authors.lastname: Speiser
authors.affiliation: Elisabeth Maritschnegg, Nina Pecha, Reinhard Horvat, Paul Speiser, and Robert Zeillinger, Medical University of Vienna, Vienna, Austria; Yuxuan Wang, Isaac Kinde, Luis A. Diaz Jr, Nickolas Papadopoulos, Kenneth W. Kinzler, and Bert Vogelstein, Johns Hopkins University, Baltimore, MD; Els Van Nieuwenhuysen and Ignace Vergote, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium; Florian Heitz, Kliniken Essen Mitte, Essen; and Jalid Sehouli, Charité Medical University, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009095:Mullerian Ducts; D009154:Mutation; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics; D010865:Pilot Projects; D016133:Polymerase Chain Reaction / Q000379:methods; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D007507:Therapeutic Irrigation / Q000379:methods; D014599:Uterus
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)