Publication

Identification of inguinofemoral lymph node metastases by methylation markers in vulvar cancer

Oonk, M. H. M., Eijsink, J. J. H., Volders, H. H., Hollema, H., Wisman, G. B. A., Schuuring, E. & van der Zee, A. G. J., May-2012, In : Gynecologic Oncology. 125, 2, p. 352-357 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Oonk, M. H. M., Eijsink, J. J. H., Volders, H. H., Hollema, H., Wisman, G. B. A., Schuuring, E., & van der Zee, A. G. J. (2012). Identification of inguinofemoral lymph node metastases by methylation markers in vulvar cancer. Gynecologic Oncology, 125(2), 352-357. https://doi.org/10.1016/j.ygyno.2012.01.013

Author

Oonk, M. H. M. ; Eijsink, J. J. H. ; Volders, H. H. ; Hollema, H. ; Wisman, G. B. A. ; Schuuring, E. ; van der Zee, A. G. J. / Identification of inguinofemoral lymph node metastases by methylation markers in vulvar cancer. In: Gynecologic Oncology. 2012 ; Vol. 125, No. 2. pp. 352-357.

Harvard

Oonk, MHM, Eijsink, JJH, Volders, HH, Hollema, H, Wisman, GBA, Schuuring, E & van der Zee, AGJ 2012, 'Identification of inguinofemoral lymph node metastases by methylation markers in vulvar cancer', Gynecologic Oncology, vol. 125, no. 2, pp. 352-357. https://doi.org/10.1016/j.ygyno.2012.01.013

Standard

Identification of inguinofemoral lymph node metastases by methylation markers in vulvar cancer. / Oonk, M. H. M.; Eijsink, J. J. H.; Volders, H. H.; Hollema, H.; Wisman, G. B. A.; Schuuring, E.; van der Zee, A. G. J.

In: Gynecologic Oncology, Vol. 125, No. 2, 05.2012, p. 352-357.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Oonk MHM, Eijsink JJH, Volders HH, Hollema H, Wisman GBA, Schuuring E et al. Identification of inguinofemoral lymph node metastases by methylation markers in vulvar cancer. Gynecologic Oncology. 2012 May;125(2):352-357. https://doi.org/10.1016/j.ygyno.2012.01.013


BibTeX

@article{4ae76e03327946f185fa1a7679cff172,
title = "Identification of inguinofemoral lymph node metastases by methylation markers in vulvar cancer",
abstract = "Objective. Lymph node status in early-stage vulvar cancer can be accurately assessed by the sentinel-node (SN) procedure. Molecular techniques, such as DNA-methylation assay, might improve SN assessment. In this study, we selected methylation markers for vulvar cancer and determined if these methylation markers were suitable for lymph node assessment.Methods. We performed methylation specific PCR on DNA isolated from primary tumors, metastatic lymph nodes, and negative lymph nodes from twenty vulvar cancer patients using the following genes: P16INK4a, MGMT, TWIST1, CADM1, TERT, and TFP12. For P16INK4a and MGMT immunohistochemistry was performed on primary tumors and metastatic lymph nodes in order to explore intratumor heterogeneity in gene expression patterns.Results. TERT was methylated in all vulvar cancers, P16INK4a in 13/20, TFP12 in 12/20, CADM1 in 11/20. MGMT in 9/20, and TWIST1 in 7/20. A panel of three methylation markers (P16INK4a, TERT and TFPI2) reached a sensitivity of 67% and specificity of 100% for detection of metastatic lymph nodes. Immunohistochemistry showed intratumor heterogeneity for expression of P16INK4a and MGMT in respectively 55% and 45% of primary tumors.Conclusions. Our study shows methylation for one or more methylation markers in all vulvar cancers. Despite a specificity of 100% our panel of three methylation markers had only moderate sensitivity for metastatic lymph node detection, thereby limiting its applicability for lymph node assessment. Intratumor heterogeneity for expression of P16INK4a and MGMT may reflect intratumor heterogeneity for methylation patterns and thereby in general explain the moderate sensitivity of our marker panel for detection of metastases. (C) 2012 Elsevier Inc. All rights reserved.",
keywords = "Vulvar cancer, Lymph node metastases, Methylation, Sentinel node, GENE PROMOTER HYPERMETHYLATION, SQUAMOUS-CELL CARCINOMA, I LUNG-CANCER, 5' CPG ISLAND, STAGE-I, O-6-METHYLGUANINE-DNA METHYLTRANSFERASE, INTRAEPITHELIAL NEOPLASIA, CERVICAL NEOPLASIA, MICROMETASTASES, INACTIVATION",
author = "Oonk, {M. H. M.} and Eijsink, {J. J. H.} and Volders, {H. H.} and H. Hollema and Wisman, {G. B. A.} and E. Schuuring and {van der Zee}, {A. G. J.}",
note = "Copyright {\textcopyright} 2012 Elsevier Inc. All rights reserved.",
year = "2012",
month = may,
doi = "10.1016/j.ygyno.2012.01.013",
language = "English",
volume = "125",
pages = "352--357",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",
number = "2",

}

RIS

TY - JOUR

T1 - Identification of inguinofemoral lymph node metastases by methylation markers in vulvar cancer

AU - Oonk, M. H. M.

AU - Eijsink, J. J. H.

AU - Volders, H. H.

AU - Hollema, H.

AU - Wisman, G. B. A.

AU - Schuuring, E.

AU - van der Zee, A. G. J.

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012/5

Y1 - 2012/5

N2 - Objective. Lymph node status in early-stage vulvar cancer can be accurately assessed by the sentinel-node (SN) procedure. Molecular techniques, such as DNA-methylation assay, might improve SN assessment. In this study, we selected methylation markers for vulvar cancer and determined if these methylation markers were suitable for lymph node assessment.Methods. We performed methylation specific PCR on DNA isolated from primary tumors, metastatic lymph nodes, and negative lymph nodes from twenty vulvar cancer patients using the following genes: P16INK4a, MGMT, TWIST1, CADM1, TERT, and TFP12. For P16INK4a and MGMT immunohistochemistry was performed on primary tumors and metastatic lymph nodes in order to explore intratumor heterogeneity in gene expression patterns.Results. TERT was methylated in all vulvar cancers, P16INK4a in 13/20, TFP12 in 12/20, CADM1 in 11/20. MGMT in 9/20, and TWIST1 in 7/20. A panel of three methylation markers (P16INK4a, TERT and TFPI2) reached a sensitivity of 67% and specificity of 100% for detection of metastatic lymph nodes. Immunohistochemistry showed intratumor heterogeneity for expression of P16INK4a and MGMT in respectively 55% and 45% of primary tumors.Conclusions. Our study shows methylation for one or more methylation markers in all vulvar cancers. Despite a specificity of 100% our panel of three methylation markers had only moderate sensitivity for metastatic lymph node detection, thereby limiting its applicability for lymph node assessment. Intratumor heterogeneity for expression of P16INK4a and MGMT may reflect intratumor heterogeneity for methylation patterns and thereby in general explain the moderate sensitivity of our marker panel for detection of metastases. (C) 2012 Elsevier Inc. All rights reserved.

AB - Objective. Lymph node status in early-stage vulvar cancer can be accurately assessed by the sentinel-node (SN) procedure. Molecular techniques, such as DNA-methylation assay, might improve SN assessment. In this study, we selected methylation markers for vulvar cancer and determined if these methylation markers were suitable for lymph node assessment.Methods. We performed methylation specific PCR on DNA isolated from primary tumors, metastatic lymph nodes, and negative lymph nodes from twenty vulvar cancer patients using the following genes: P16INK4a, MGMT, TWIST1, CADM1, TERT, and TFP12. For P16INK4a and MGMT immunohistochemistry was performed on primary tumors and metastatic lymph nodes in order to explore intratumor heterogeneity in gene expression patterns.Results. TERT was methylated in all vulvar cancers, P16INK4a in 13/20, TFP12 in 12/20, CADM1 in 11/20. MGMT in 9/20, and TWIST1 in 7/20. A panel of three methylation markers (P16INK4a, TERT and TFPI2) reached a sensitivity of 67% and specificity of 100% for detection of metastatic lymph nodes. Immunohistochemistry showed intratumor heterogeneity for expression of P16INK4a and MGMT in respectively 55% and 45% of primary tumors.Conclusions. Our study shows methylation for one or more methylation markers in all vulvar cancers. Despite a specificity of 100% our panel of three methylation markers had only moderate sensitivity for metastatic lymph node detection, thereby limiting its applicability for lymph node assessment. Intratumor heterogeneity for expression of P16INK4a and MGMT may reflect intratumor heterogeneity for methylation patterns and thereby in general explain the moderate sensitivity of our marker panel for detection of metastases. (C) 2012 Elsevier Inc. All rights reserved.

KW - Vulvar cancer

KW - Lymph node metastases

KW - Methylation

KW - Sentinel node

KW - GENE PROMOTER HYPERMETHYLATION

KW - SQUAMOUS-CELL CARCINOMA

KW - I LUNG-CANCER

KW - 5' CPG ISLAND

KW - STAGE-I

KW - O-6-METHYLGUANINE-DNA METHYLTRANSFERASE

KW - INTRAEPITHELIAL NEOPLASIA

KW - CERVICAL NEOPLASIA

KW - MICROMETASTASES

KW - INACTIVATION

U2 - 10.1016/j.ygyno.2012.01.013

DO - 10.1016/j.ygyno.2012.01.013

M3 - Article

C2 - 22266550

VL - 125

SP - 352

EP - 357

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -

ID: 5552267