Skip to main content
Top
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Study protocol

PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study, pre-operative recognition of high risk endometrial carcinoma: a multicentre prospective cohort study

Authors: Nicole C. M. Visser, Johan Bulten, Anneke A. M. van der Wurff, Erik A. Boss, Carolien M. Bronkhorst, Harrie W. H. Feijen, Joke E. Haartsen, Hilde A. D. M. van Herk, Ineke M. de Kievit, Paul J. J. M. Klinkhamer, Brenda M. Pijlman, Marc P. M. L. Snijders, Ingrid Vandenput, M. Caroline Vos, Peter E. J. de Wit, Lonneke V. van de Poll-Franse, Leon F.A.G. Massuger, Johanna M. A. Pijnenborg

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Endometrial carcinoma is the most common gynaecologic malignancy in industrialised countries and the incidence is still rising. Primary treatment is based on preoperative risk classification and consists in most cases of hysterectomy with bilateral salpingo-oophorectomy. In patients with serous and clear cell histology a complete surgical staging is mandatory. However, in routine clinical practice final histology regularly does not correspond with the preoperative histological diagnosis. This results in both over and under treatment.

Methods/Design

The aim of this multicentre, prospective cohort study is to select a panel of prognostic biomarkers to improve preoperative diagnosis of endometrial carcinoma in order to identify those patients that need extended surgery and/or additional treatment. Additionally, we will determine whether incorporation of cervical cytology and comorbidity could improve this preoperative risk classification. All patients treated for endometrial carcinoma in the participating hospitals from September 2011 till December 2013 are included. Patient characteristics, as well as comorbidity are registered. Patients without preoperative histology, history of hysterectomy and/or endometrial carcinoma or no surgical treatment including hysterectomy are excluded. The preoperative histology and final pathology will be reviewed and compared by expert pathologists. Additional immunohistochemical analysis of IMP3, p53, ER, PR, MLH1, PTEN, beta-catenin, p16, Ki-67, stathmin, ARID1A and L1CAM will be performed. Preoperative histology will be compared with the final pathology results. Follow-up will be at least 24 months to determine risk factors for recurrence and outcome.

Discussion

This study is designed to improve surgical treatment of endometrial carcinoma patients. A total of 432 endometrial carcinoma patients were enrolled between 2011 and 2013. Follow-up will be completed in 2015. Preoperative histology will be evaluated systematically and background endometrium will be classified. This is the first study incorporating immunohistochemistry, cervical cytology and comorbidity to define the optimal panel of prognostic biomarkers that contribute in clinical decision making in the management of endometrial carcinoma.

Trial registration

Netherlands Trial Register number NTR3503
Literature
1.
3.
go back to reference Boll D, Karim-Kos HE, Verhoeven RH, Burger CW, Coebergh JW, van de Poll-Franse LV, et al. Increased incidence and improved survival in endometrioid endometrial cancer diagnosed since 1989 in The Netherlands: a population based study. Eur J Obstet Gynecol Reprod Biol. 2013;166(2):209–14.CrossRefPubMed Boll D, Karim-Kos HE, Verhoeven RH, Burger CW, Coebergh JW, van de Poll-Franse LV, et al. Increased incidence and improved survival in endometrioid endometrial cancer diagnosed since 1989 in The Netherlands: a population based study. Eur J Obstet Gynecol Reprod Biol. 2013;166(2):209–14.CrossRefPubMed
4.
go back to reference Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet. 2006;95 Suppl 1:S105–43.CrossRef Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet. 2006;95 Suppl 1:S105–43.CrossRef
5.
6.
go back to reference Geels YP, Pijnenborg JM, van den Berg-van Erp SH, Bulten J, Visscher DW, Dowdy SC, et al. Endometrioid endometrial carcinoma with atrophic endometrium and poor prognosis. Obstet Gynecol. 2012;120(5):1124–31.PubMed Geels YP, Pijnenborg JM, van den Berg-van Erp SH, Bulten J, Visscher DW, Dowdy SC, et al. Endometrioid endometrial carcinoma with atrophic endometrium and poor prognosis. Obstet Gynecol. 2012;120(5):1124–31.PubMed
7.
go back to reference Cancer Genome Atlas Research N, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.CrossRef Cancer Genome Atlas Research N, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73.CrossRef
9.
go back to reference Boruta 2nd DM, Gehrig PA, Fader AN, Olawaiye AB. Management of women with uterine papillary serous cancer: a Society of Gynecologic Oncology (SGO) review. Gynecol Oncol. 2009;115(1):142–53.CrossRefPubMed Boruta 2nd DM, Gehrig PA, Fader AN, Olawaiye AB. Management of women with uterine papillary serous cancer: a Society of Gynecologic Oncology (SGO) review. Gynecol Oncol. 2009;115(1):142–53.CrossRefPubMed
10.
go back to reference Olawaiye AB, Boruta 2nd DM. Management of women with clear cell endometrial cancer: a Society of Gynecologic Oncology (SGO) review. Gynecol Oncol. 2009;113(2):277–83.CrossRefPubMed Olawaiye AB, Boruta 2nd DM. Management of women with clear cell endometrial cancer: a Society of Gynecologic Oncology (SGO) review. Gynecol Oncol. 2009;113(2):277–83.CrossRefPubMed
11.
go back to reference Kwon JS, Qiu F, Saskin R, Carey MS. Are uterine risk factors more important than nodal status in predicting survival in endometrial cancer? Obstet Gynecol. 2009;114(4):736–43.CrossRefPubMed Kwon JS, Qiu F, Saskin R, Carey MS. Are uterine risk factors more important than nodal status in predicting survival in endometrial cancer? Obstet Gynecol. 2009;114(4):736–43.CrossRefPubMed
12.
go back to reference Visser NC, Breijer MC, Herman MC, Bekkers RL, Veersema S, Opmeer BC, et al. Factors attributing to the failure of endometrial sampling in women with postmenopausal bleeding. Acta Obstet Gynecol Scand. 2013;92(10):1216–22.PubMed Visser NC, Breijer MC, Herman MC, Bekkers RL, Veersema S, Opmeer BC, et al. Factors attributing to the failure of endometrial sampling in women with postmenopausal bleeding. Acta Obstet Gynecol Scand. 2013;92(10):1216–22.PubMed
13.
go back to reference Petersen RW, Quinlivan JA, Casper GR, Nicklin JL. Endometrial adenocarcinoma—presenting pathology is a poor guide to surgical management. Aust N Z J Obstet Gynaecol. 2000;40(2):191–4.CrossRefPubMed Petersen RW, Quinlivan JA, Casper GR, Nicklin JL. Endometrial adenocarcinoma—presenting pathology is a poor guide to surgical management. Aust N Z J Obstet Gynaecol. 2000;40(2):191–4.CrossRefPubMed
14.
go back to reference Frumovitz M, Singh DK, Meyer L, Smith DH, Wertheim I, Resnik E, et al. Predictors of final histology in patients with endometrial cancer. Gynecol Oncol. 2004;95(3):463–8.CrossRefPubMed Frumovitz M, Singh DK, Meyer L, Smith DH, Wertheim I, Resnik E, et al. Predictors of final histology in patients with endometrial cancer. Gynecol Oncol. 2004;95(3):463–8.CrossRefPubMed
15.
go back to reference Leitao Jr MM, Kehoe S, Barakat RR, Alektiar K, Gattoc LP, Rabbitt C, et al. Accuracy of preoperative endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol. 2008;111(2):244–8.CrossRefPubMed Leitao Jr MM, Kehoe S, Barakat RR, Alektiar K, Gattoc LP, Rabbitt C, et al. Accuracy of preoperative endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol. 2008;111(2):244–8.CrossRefPubMed
16.
go back to reference Neubauer NL, Havrilesky LJ, Calingaert B, Bulusu A, Bernardini MQ, Fleming ND, et al. The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma. Gynecol Oncol. 2009;112(3):511–6.CrossRefPubMed Neubauer NL, Havrilesky LJ, Calingaert B, Bulusu A, Bernardini MQ, Fleming ND, et al. The role of lymphadenectomy in the management of preoperative grade 1 endometrial carcinoma. Gynecol Oncol. 2009;112(3):511–6.CrossRefPubMed
17.
go back to reference Helpman L, Kupets R, Covens A, Saad RS, Khalifa MA, Ismiil N, et al. Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer. Br J Cancer. 2014;110(3):609–15.CrossRefPubMed Helpman L, Kupets R, Covens A, Saad RS, Khalifa MA, Ismiil N, et al. Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer. Br J Cancer. 2014;110(3):609–15.CrossRefPubMed
18.
go back to reference Leitao Jr MM, Kehoe S, Barakat RR, Alektiar K, Gattoc LP, Rabbitt C, et al. Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol. 2009;113(1):105–8.CrossRefPubMed Leitao Jr MM, Kehoe S, Barakat RR, Alektiar K, Gattoc LP, Rabbitt C, et al. Comparison of D&C and office endometrial biopsy accuracy in patients with FIGO grade 1 endometrial adenocarcinoma. Gynecol Oncol. 2009;113(1):105–8.CrossRefPubMed
19.
go back to reference Mhawech-Fauceglia P, Herrmann FR, Rai H, Tchabo N, Lele S, Izevbaye I, et al. IMP3 distinguishes uterine serous carcinoma from endometrial endometrioid adenocarcinoma. Am J Clin Pathol. 2010;133(6):899–908.CrossRefPubMed Mhawech-Fauceglia P, Herrmann FR, Rai H, Tchabo N, Lele S, Izevbaye I, et al. IMP3 distinguishes uterine serous carcinoma from endometrial endometrioid adenocarcinoma. Am J Clin Pathol. 2010;133(6):899–908.CrossRefPubMed
20.
go back to reference Trovik J, Wik E, Werner HM, Krakstad C, Helland H, Vandenput I, et al. Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial. Eur J Cancer. 2013;49(16):3431–41.CrossRefPubMed Trovik J, Wik E, Werner HM, Krakstad C, Helland H, Vandenput I, et al. Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial. Eur J Cancer. 2013;49(16):3431–41.CrossRefPubMed
21.
go back to reference Mhawech-Fauceglia P, Yan L, Liu S, Pejovic T. ER+ /PR+ /TFF3+ /IMP3- immunoprofile distinguishes endometrioid from serous and clear cell carcinomas of the endometrium: a study of 401 cases. Histopathology. 2013;62(7):976–85.CrossRefPubMed Mhawech-Fauceglia P, Yan L, Liu S, Pejovic T. ER+ /PR+ /TFF3+ /IMP3- immunoprofile distinguishes endometrioid from serous and clear cell carcinomas of the endometrium: a study of 401 cases. Histopathology. 2013;62(7):976–85.CrossRefPubMed
22.
go back to reference Zeimet AG, Reimer D, Huszar M, Winterhoff B, Puistola U, Azim SA, et al. L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation. J Natl Cancer Inst. 2013;105(15):1142–50.CrossRefPubMed Zeimet AG, Reimer D, Huszar M, Winterhoff B, Puistola U, Azim SA, et al. L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation. J Natl Cancer Inst. 2013;105(15):1142–50.CrossRefPubMed
23.
go back to reference Siebers AG, Verbeek AL, Massuger LF, Grefte JM, Bulten J. Normal appearing endometrial cells in cervical smears of asymptomatic postmenopausal women have predictive value for significant endometrial pathology. Int J Gynecol Cancer. 2006;16(3):1069–74.CrossRefPubMed Siebers AG, Verbeek AL, Massuger LF, Grefte JM, Bulten J. Normal appearing endometrial cells in cervical smears of asymptomatic postmenopausal women have predictive value for significant endometrial pathology. Int J Gynecol Cancer. 2006;16(3):1069–74.CrossRefPubMed
24.
go back to reference Roelofsen T, Geels YP, Pijnenborg JM, van Ham MA, Zomer SF, van Tilburg JM, et al. Cervical cytology in serous and endometrioid endometrial cancer. Int J Gynecol Pathol. 2013;32(4):390–8.CrossRefPubMed Roelofsen T, Geels YP, Pijnenborg JM, van Ham MA, Zomer SF, van Tilburg JM, et al. Cervical cytology in serous and endometrioid endometrial cancer. Int J Gynecol Pathol. 2013;32(4):390–8.CrossRefPubMed
25.
go back to reference Kinde I, Bettegowda C, Wang Y, Wu J, Agrawal N, Shih Ie M, et al. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med. 2013;5(167):167ra164.CrossRef Kinde I, Bettegowda C, Wang Y, Wu J, Agrawal N, Shih Ie M, et al. Evaluation of DNA from the Papanicolaou test to detect ovarian and endometrial cancers. Sci Transl Med. 2013;5(167):167ra164.CrossRef
26.
go back to reference Boll D, Verhoeven RH, van der Aa MA, Lybeert ML, Coebergh JW, Janssen-Heijnen ML. Adherence to national guidelines for treatment and outcome of endometrial cancer stage I in relation to co-morbidity in southern Netherlands 1995–2008. Eur J Cancer. 2011;47(10):1504–10.CrossRefPubMed Boll D, Verhoeven RH, van der Aa MA, Lybeert ML, Coebergh JW, Janssen-Heijnen ML. Adherence to national guidelines for treatment and outcome of endometrial cancer stage I in relation to co-morbidity in southern Netherlands 1995–2008. Eur J Cancer. 2011;47(10):1504–10.CrossRefPubMed
27.
go back to reference Zanders MM, Boll D, van Steenbergen LN, van de Poll-Franse LV, Haak HR. Effect of diabetes on endometrial cancer recurrence and survival. Maturitas. 2013;74(1):37–43.CrossRefPubMed Zanders MM, Boll D, van Steenbergen LN, van de Poll-Franse LV, Haak HR. Effect of diabetes on endometrial cancer recurrence and survival. Maturitas. 2013;74(1):37–43.CrossRefPubMed
28.
go back to reference Liao C, Zhang D, Mungo C, Tompkins DA, Zeidan AM. Is diabetes mellitus associated with increased incidence and disease-specific mortality in endometrial cancer? A systematic review and meta-analysis of cohort studies. Gynecol Oncol. 2014;135(1):163–71.CrossRefPubMedPubMedCentral Liao C, Zhang D, Mungo C, Tompkins DA, Zeidan AM. Is diabetes mellitus associated with increased incidence and disease-specific mortality in endometrial cancer? A systematic review and meta-analysis of cohort studies. Gynecol Oncol. 2014;135(1):163–71.CrossRefPubMedPubMedCentral
29.
go back to reference Nevadunsky NS, Van Arsdale A, Strickler HD, Moadel A, Kaur G, Levitt J, et al. Obesity and age at diagnosis of endometrial cancer. Obstet Gynecol. 2014;124(2 Pt 1):300–6.CrossRefPubMed Nevadunsky NS, Van Arsdale A, Strickler HD, Moadel A, Kaur G, Levitt J, et al. Obesity and age at diagnosis of endometrial cancer. Obstet Gynecol. 2014;124(2 Pt 1):300–6.CrossRefPubMed
30.
go back to reference Robbins JR, Gayar OH, Zaki M, Mahan M, Buekers T, Elshaikh MA. Impact of age-adjusted Charlson comorbidity score on outcomes for patients with early-stage endometrial cancer. Gynecol Oncol. 2013;131(3):593–7.CrossRefPubMed Robbins JR, Gayar OH, Zaki M, Mahan M, Buekers T, Elshaikh MA. Impact of age-adjusted Charlson comorbidity score on outcomes for patients with early-stage endometrial cancer. Gynecol Oncol. 2013;131(3):593–7.CrossRefPubMed
31.
go back to reference Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51.CrossRefPubMed Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51.CrossRefPubMed
32.
go back to reference Boll D, Verhoeven RH, van der Aa MA, Pauwels P, Karim-Kos HE, Coebergh JW, et al. Incidence and survival trends of uncommon corpus uteri malignancies in the Netherlands, 1989–2008. Int J Gynecol Cancer. 2012;22(4):599–606.CrossRefPubMed Boll D, Verhoeven RH, van der Aa MA, Pauwels P, Karim-Kos HE, Coebergh JW, et al. Incidence and survival trends of uncommon corpus uteri malignancies in the Netherlands, 1989–2008. Int J Gynecol Cancer. 2012;22(4):599–606.CrossRefPubMed
33.
go back to reference Huang GS, Gebb JS, Einstein MH, Shahabi S, Novetsky AP, Goldberg GL. Accuracy of preoperative endometrial sampling for the detection of high-grade endometrial tumors. Am J Obstet Gynecol. 2007;196(3):243. e241–245.CrossRefPubMed Huang GS, Gebb JS, Einstein MH, Shahabi S, Novetsky AP, Goldberg GL. Accuracy of preoperative endometrial sampling for the detection of high-grade endometrial tumors. Am J Obstet Gynecol. 2007;196(3):243. e241–245.CrossRefPubMed
34.
go back to reference Lax SF, Pizer ES, Ronnett BM, Kurman RJ. Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression. Hum Pathol. 1998;29(6):551–8.CrossRefPubMed Lax SF, Pizer ES, Ronnett BM, Kurman RJ. Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression. Hum Pathol. 1998;29(6):551–8.CrossRefPubMed
35.
go back to reference Nelson GS, Pink A, Lee S, Han G, Morris D, Ogilvie T, et al. MMR deficiency is common in high-grade endometrioid carcinomas and is associated with an unfavorable outcome. Gynecol Oncol. 2013;131(2):309–14.CrossRefPubMed Nelson GS, Pink A, Lee S, Han G, Morris D, Ogilvie T, et al. MMR deficiency is common in high-grade endometrioid carcinomas and is associated with an unfavorable outcome. Gynecol Oncol. 2013;131(2):309–14.CrossRefPubMed
36.
go back to reference Peiro G, Diebold J, Mayr D, Baretton GB, Kimmig R, Schmidt M, et al. Prognostic relevance of hMLH1, hMSH2, and BAX protein expression in endometrial carcinoma. Mod Pathol. 2001;14(8):777–83.CrossRefPubMed Peiro G, Diebold J, Mayr D, Baretton GB, Kimmig R, Schmidt M, et al. Prognostic relevance of hMLH1, hMSH2, and BAX protein expression in endometrial carcinoma. Mod Pathol. 2001;14(8):777–83.CrossRefPubMed
37.
go back to reference Athanassiadou P, Athanassiades P, Grapsa D, Gonidi M, Athanassiadou AM, Stamati PN, et al. The prognostic value of PTEN, p53, and beta-catenin in endometrial carcinoma: a prospective immunocytochemical study. Int J Gynecol Cancer. 2007;17(3):697–704.CrossRefPubMed Athanassiadou P, Athanassiades P, Grapsa D, Gonidi M, Athanassiadou AM, Stamati PN, et al. The prognostic value of PTEN, p53, and beta-catenin in endometrial carcinoma: a prospective immunocytochemical study. Int J Gynecol Cancer. 2007;17(3):697–704.CrossRefPubMed
38.
go back to reference Engelsen IB, Stefansson I, Akslen LA, Salvesen HB. Pathologic expression of p53 or p16 in preoperative curettage specimens identifies high-risk endometrial carcinomas. Am J Obstet Gynecol. 2006;195(4):979–86.CrossRefPubMed Engelsen IB, Stefansson I, Akslen LA, Salvesen HB. Pathologic expression of p53 or p16 in preoperative curettage specimens identifies high-risk endometrial carcinomas. Am J Obstet Gynecol. 2006;195(4):979–86.CrossRefPubMed
39.
go back to reference Trovik J, Wik E, Stefansson IM, Marcickiewicz J, Tingulstad S, Staff AC, et al. Stathmin overexpression identifies high-risk patients and lymph node metastasis in endometrial cancer. Clin Cancer Res. 2011;17(10):3368–77.CrossRefPubMed Trovik J, Wik E, Stefansson IM, Marcickiewicz J, Tingulstad S, Staff AC, et al. Stathmin overexpression identifies high-risk patients and lymph node metastasis in endometrial cancer. Clin Cancer Res. 2011;17(10):3368–77.CrossRefPubMed
40.
go back to reference Allo G, Bernardini MQ, Wu RC, Shih Ie M, Kalloger S, Pollett A, et al. ARID1A loss correlates with mismatch repair deficiency and intact p53 expression in high-grade endometrial carcinomas. Mod Pathol. 2014;27(2):255–61.CrossRefPubMed Allo G, Bernardini MQ, Wu RC, Shih Ie M, Kalloger S, Pollett A, et al. ARID1A loss correlates with mismatch repair deficiency and intact p53 expression in high-grade endometrial carcinomas. Mod Pathol. 2014;27(2):255–61.CrossRefPubMed
Metadata
Title
PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study, pre-operative recognition of high risk endometrial carcinoma: a multicentre prospective cohort study
Authors
Nicole C. M. Visser
Johan Bulten
Anneke A. M. van der Wurff
Erik A. Boss
Carolien M. Bronkhorst
Harrie W. H. Feijen
Joke E. Haartsen
Hilde A. D. M. van Herk
Ineke M. de Kievit
Paul J. J. M. Klinkhamer
Brenda M. Pijlman
Marc P. M. L. Snijders
Ingrid Vandenput
M. Caroline Vos
Peter E. J. de Wit
Lonneke V. van de Poll-Franse
Leon F.A.G. Massuger
Johanna M. A. Pijnenborg
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1487-3

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine