Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons

Jamie N Bakkum-Gamez, Nicolas Wentzensen, Matthew J. Maurer, Kieran M. Hawthorne, Jesse S. Voss, Trynda N. Kroneman, Abimbola O. Famuyide, Amy C. Clayton, Kevin C. Halling, Sarah E. Kerr, William Arthur Cliby, Sean Christopher Dowdy, Benjamin R. Kipp, Andrea Mariani, Ann L Oberg, Karl C. Podratz, Vijayalakshmi Shridhar, Mark E. Sherman

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objective. We demonstrate the feasibility of detecting EC by combining minimally-invasive specimen collection techniques with sensitive molecular testing. Methods. Prior to hysterectomy for EC or benign indications, women collected vaginal pool samples with intravaginal tampons and underwent endometrial brushing. Specimens underwent pyrosequencing for DNA methylation of genes reported to be hypermethylated in gynecologic cancers and recently identified markers discovered by profiling over 200 ECs. Methylation was evaluated individually across CpGs and averaged across genes. Differences between EC and benign endometrium (BE) were assessed using two-sample t-tests and area under the curve (AUC). Results. Thirty-eight ECs and 28 BEswere included. We evaluated 97 CpGswithin 12 genes, including previously reported markers (RASSF1, HSP2A, HOXA9, CDH13, HAAO, and GTF2A1) and those identified in discovery work (ASCL2, HTR1B, NPY, HS3ST2, MME, ADCYAP1, and additional CDH13 CpG sites). Mean methylation was higher in tampon specimens from EC v. BE for 9 of 12 genes (ADCYAP1, ASCL2, CDH13, HS3ST2, HTR1B, MME, HAAO, HOXA9, and RASSF1) (all p < 0.05). Among these genes, relative hypermethylation was observed in EC v. BE across CpGs. Endometrial brush and tampon results were similar. Within tampon specimens, AUC was highest for HTR1B (0.82), RASSF1 (0.75), and HOXA9 (0.74). This is the first report of HOXA9 hypermethylation in EC. Conclusion. DNA hypermethylation in EC tissues can also be identified in vaginal pool DNA collected via intravaginal tampon. Identification of additional EC biomarkers and refined collection methods are needed to develop an early detection tool for EC.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
JournalGynecologic Oncology
Volume137
Issue number1
DOIs
StatePublished - 2015

Fingerprint

Menstrual Hygiene Products
Endometrial Neoplasms
Endometrium
DNA
Genes
Methylation
Area Under Curve
Specimen Handling
DNA Methylation
Hysterectomy
Biomarkers

Keywords

  • Early detection
  • Endometrial cancer
  • Methylation
  • Tampon
  • Tao brush

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons. / Bakkum-Gamez, Jamie N; Wentzensen, Nicolas; Maurer, Matthew J.; Hawthorne, Kieran M.; Voss, Jesse S.; Kroneman, Trynda N.; Famuyide, Abimbola O.; Clayton, Amy C.; Halling, Kevin C.; Kerr, Sarah E.; Cliby, William Arthur; Dowdy, Sean Christopher; Kipp, Benjamin R.; Mariani, Andrea; Oberg, Ann L; Podratz, Karl C.; Shridhar, Vijayalakshmi; Sherman, Mark E.

In: Gynecologic Oncology, Vol. 137, No. 1, 2015, p. 14-22.

Research output: Contribution to journalArticle

Bakkum-Gamez, JN, Wentzensen, N, Maurer, MJ, Hawthorne, KM, Voss, JS, Kroneman, TN, Famuyide, AO, Clayton, AC, Halling, KC, Kerr, SE, Cliby, WA, Dowdy, SC, Kipp, BR, Mariani, A, Oberg, AL, Podratz, KC, Shridhar, V & Sherman, ME 2015, 'Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons', Gynecologic Oncology, vol. 137, no. 1, pp. 14-22. https://doi.org/10.1016/j.ygyno.2015.01.552
Bakkum-Gamez, Jamie N ; Wentzensen, Nicolas ; Maurer, Matthew J. ; Hawthorne, Kieran M. ; Voss, Jesse S. ; Kroneman, Trynda N. ; Famuyide, Abimbola O. ; Clayton, Amy C. ; Halling, Kevin C. ; Kerr, Sarah E. ; Cliby, William Arthur ; Dowdy, Sean Christopher ; Kipp, Benjamin R. ; Mariani, Andrea ; Oberg, Ann L ; Podratz, Karl C. ; Shridhar, Vijayalakshmi ; Sherman, Mark E. / Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons. In: Gynecologic Oncology. 2015 ; Vol. 137, No. 1. pp. 14-22.
@article{d6cf80d3b67948c0820c568127c31cf0,
title = "Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons",
abstract = "Objective. We demonstrate the feasibility of detecting EC by combining minimally-invasive specimen collection techniques with sensitive molecular testing. Methods. Prior to hysterectomy for EC or benign indications, women collected vaginal pool samples with intravaginal tampons and underwent endometrial brushing. Specimens underwent pyrosequencing for DNA methylation of genes reported to be hypermethylated in gynecologic cancers and recently identified markers discovered by profiling over 200 ECs. Methylation was evaluated individually across CpGs and averaged across genes. Differences between EC and benign endometrium (BE) were assessed using two-sample t-tests and area under the curve (AUC). Results. Thirty-eight ECs and 28 BEswere included. We evaluated 97 CpGswithin 12 genes, including previously reported markers (RASSF1, HSP2A, HOXA9, CDH13, HAAO, and GTF2A1) and those identified in discovery work (ASCL2, HTR1B, NPY, HS3ST2, MME, ADCYAP1, and additional CDH13 CpG sites). Mean methylation was higher in tampon specimens from EC v. BE for 9 of 12 genes (ADCYAP1, ASCL2, CDH13, HS3ST2, HTR1B, MME, HAAO, HOXA9, and RASSF1) (all p < 0.05). Among these genes, relative hypermethylation was observed in EC v. BE across CpGs. Endometrial brush and tampon results were similar. Within tampon specimens, AUC was highest for HTR1B (0.82), RASSF1 (0.75), and HOXA9 (0.74). This is the first report of HOXA9 hypermethylation in EC. Conclusion. DNA hypermethylation in EC tissues can also be identified in vaginal pool DNA collected via intravaginal tampon. Identification of additional EC biomarkers and refined collection methods are needed to develop an early detection tool for EC.",
keywords = "Early detection, Endometrial cancer, Methylation, Tampon, Tao brush",
author = "Bakkum-Gamez, {Jamie N} and Nicolas Wentzensen and Maurer, {Matthew J.} and Hawthorne, {Kieran M.} and Voss, {Jesse S.} and Kroneman, {Trynda N.} and Famuyide, {Abimbola O.} and Clayton, {Amy C.} and Halling, {Kevin C.} and Kerr, {Sarah E.} and Cliby, {William Arthur} and Dowdy, {Sean Christopher} and Kipp, {Benjamin R.} and Andrea Mariani and Oberg, {Ann L} and Podratz, {Karl C.} and Vijayalakshmi Shridhar and Sherman, {Mark E.}",
year = "2015",
doi = "10.1016/j.ygyno.2015.01.552",
language = "English (US)",
volume = "137",
pages = "14--22",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Detection of endometrial cancer via molecular analysis of DNA collected with vaginal tampons

AU - Bakkum-Gamez, Jamie N

AU - Wentzensen, Nicolas

AU - Maurer, Matthew J.

AU - Hawthorne, Kieran M.

AU - Voss, Jesse S.

AU - Kroneman, Trynda N.

AU - Famuyide, Abimbola O.

AU - Clayton, Amy C.

AU - Halling, Kevin C.

AU - Kerr, Sarah E.

AU - Cliby, William Arthur

AU - Dowdy, Sean Christopher

AU - Kipp, Benjamin R.

AU - Mariani, Andrea

AU - Oberg, Ann L

AU - Podratz, Karl C.

AU - Shridhar, Vijayalakshmi

AU - Sherman, Mark E.

PY - 2015

Y1 - 2015

N2 - Objective. We demonstrate the feasibility of detecting EC by combining minimally-invasive specimen collection techniques with sensitive molecular testing. Methods. Prior to hysterectomy for EC or benign indications, women collected vaginal pool samples with intravaginal tampons and underwent endometrial brushing. Specimens underwent pyrosequencing for DNA methylation of genes reported to be hypermethylated in gynecologic cancers and recently identified markers discovered by profiling over 200 ECs. Methylation was evaluated individually across CpGs and averaged across genes. Differences between EC and benign endometrium (BE) were assessed using two-sample t-tests and area under the curve (AUC). Results. Thirty-eight ECs and 28 BEswere included. We evaluated 97 CpGswithin 12 genes, including previously reported markers (RASSF1, HSP2A, HOXA9, CDH13, HAAO, and GTF2A1) and those identified in discovery work (ASCL2, HTR1B, NPY, HS3ST2, MME, ADCYAP1, and additional CDH13 CpG sites). Mean methylation was higher in tampon specimens from EC v. BE for 9 of 12 genes (ADCYAP1, ASCL2, CDH13, HS3ST2, HTR1B, MME, HAAO, HOXA9, and RASSF1) (all p < 0.05). Among these genes, relative hypermethylation was observed in EC v. BE across CpGs. Endometrial brush and tampon results were similar. Within tampon specimens, AUC was highest for HTR1B (0.82), RASSF1 (0.75), and HOXA9 (0.74). This is the first report of HOXA9 hypermethylation in EC. Conclusion. DNA hypermethylation in EC tissues can also be identified in vaginal pool DNA collected via intravaginal tampon. Identification of additional EC biomarkers and refined collection methods are needed to develop an early detection tool for EC.

AB - Objective. We demonstrate the feasibility of detecting EC by combining minimally-invasive specimen collection techniques with sensitive molecular testing. Methods. Prior to hysterectomy for EC or benign indications, women collected vaginal pool samples with intravaginal tampons and underwent endometrial brushing. Specimens underwent pyrosequencing for DNA methylation of genes reported to be hypermethylated in gynecologic cancers and recently identified markers discovered by profiling over 200 ECs. Methylation was evaluated individually across CpGs and averaged across genes. Differences between EC and benign endometrium (BE) were assessed using two-sample t-tests and area under the curve (AUC). Results. Thirty-eight ECs and 28 BEswere included. We evaluated 97 CpGswithin 12 genes, including previously reported markers (RASSF1, HSP2A, HOXA9, CDH13, HAAO, and GTF2A1) and those identified in discovery work (ASCL2, HTR1B, NPY, HS3ST2, MME, ADCYAP1, and additional CDH13 CpG sites). Mean methylation was higher in tampon specimens from EC v. BE for 9 of 12 genes (ADCYAP1, ASCL2, CDH13, HS3ST2, HTR1B, MME, HAAO, HOXA9, and RASSF1) (all p < 0.05). Among these genes, relative hypermethylation was observed in EC v. BE across CpGs. Endometrial brush and tampon results were similar. Within tampon specimens, AUC was highest for HTR1B (0.82), RASSF1 (0.75), and HOXA9 (0.74). This is the first report of HOXA9 hypermethylation in EC. Conclusion. DNA hypermethylation in EC tissues can also be identified in vaginal pool DNA collected via intravaginal tampon. Identification of additional EC biomarkers and refined collection methods are needed to develop an early detection tool for EC.

KW - Early detection

KW - Endometrial cancer

KW - Methylation

KW - Tampon

KW - Tao brush

UR - http://www.scopus.com/inward/record.url?scp=84933182501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84933182501&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2015.01.552

DO - 10.1016/j.ygyno.2015.01.552

M3 - Article

C2 - 25677060

AN - SCOPUS:84933182501

VL - 137

SP - 14

EP - 22

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 1

ER -