Lavage of the uterine cavity for molecular detection of Müllerian duct carcinomas: A proof-of-concept study

Elisabeth Maritschnegg, Yuxuan Wang, Nina Pecha, Reinhard Horvat, Els Van Nieuwenhuysen, Ignace Vergote, Florian Heitz, Jalid Sehouli, Isaac Kinde, Luis A. Diaz, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Paul Speiser, Robert Zeillinger

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)4293-4300
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number36
DOIs
StatePublished - Dec 20 2015

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Therapeutic Irrigation
Ovarian Neoplasms
Carcinoma
Mutation
Endometrial Neoplasms
Neoplasms
High-Throughput Nucleotide Sequencing
Early Diagnosis
Survival Rate
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Maritschnegg, E., Wang, Y., Pecha, N., Horvat, R., Van Nieuwenhuysen, E., Vergote, I., ... Zeillinger, R. (2015). Lavage of the uterine cavity for molecular detection of Müllerian duct carcinomas: A proof-of-concept study. Journal of Clinical Oncology, 33(36), 4293-4300. https://doi.org/10.1200/JCO.2015.61.3083

Lavage of the uterine cavity for molecular detection of Müllerian duct carcinomas : A proof-of-concept study. / Maritschnegg, Elisabeth; Wang, Yuxuan; Pecha, Nina; Horvat, Reinhard; Van Nieuwenhuysen, Els; Vergote, Ignace; Heitz, Florian; Sehouli, Jalid; Kinde, Isaac; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Speiser, Paul; Zeillinger, Robert.

In: Journal of Clinical Oncology, Vol. 33, No. 36, 20.12.2015, p. 4293-4300.

Research output: Contribution to journalArticle

Maritschnegg, E, Wang, Y, Pecha, N, Horvat, R, Van Nieuwenhuysen, E, Vergote, I, Heitz, F, Sehouli, J, Kinde, I, Diaz, LA, Papadopoulos, N, Kinzler, KW, Vogelstein, B, Speiser, P & Zeillinger, R 2015, 'Lavage of the uterine cavity for molecular detection of Müllerian duct carcinomas: A proof-of-concept study', Journal of Clinical Oncology, vol. 33, no. 36, pp. 4293-4300. https://doi.org/10.1200/JCO.2015.61.3083
Maritschnegg, Elisabeth ; Wang, Yuxuan ; Pecha, Nina ; Horvat, Reinhard ; Van Nieuwenhuysen, Els ; Vergote, Ignace ; Heitz, Florian ; Sehouli, Jalid ; Kinde, Isaac ; Diaz, Luis A. ; Papadopoulos, Nickolas ; Kinzler, Kenneth W ; Vogelstein, Bert ; Speiser, Paul ; Zeillinger, Robert. / Lavage of the uterine cavity for molecular detection of Müllerian duct carcinomas : A proof-of-concept study. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 36. pp. 4293-4300.
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abstract = "Purpose: 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 M{\"u}llerian duct cancers may exfoliate cells. We have established an approach for lavage of the uterine cavity to detect shed cancer cells. Patients and 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. Conclusion: 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.",
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T1 - Lavage of the uterine cavity for molecular detection of Müllerian duct carcinomas

T2 - A proof-of-concept study

AU - Maritschnegg, Elisabeth

AU - Wang, Yuxuan

AU - Pecha, Nina

AU - Horvat, Reinhard

AU - Van Nieuwenhuysen, Els

AU - Vergote, Ignace

AU - Heitz, Florian

AU - Sehouli, Jalid

AU - Kinde, Isaac

AU - Diaz, Luis A.

AU - Papadopoulos, Nickolas

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - Speiser, Paul

AU - Zeillinger, Robert

PY - 2015/12/20

Y1 - 2015/12/20

N2 - Purpose: 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. Patients and 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. Conclusion: 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.

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