Elsevier

Gynecologic Oncology

Volume 131, Issue 2, November 2013, Pages 304-308
Gynecologic Oncology

The additional value of endometrial sampling in the early detection of endometrial cancer in women with Lynch syndrome

https://doi.org/10.1016/j.ygyno.2013.05.032Get rights and content

Highlights

  • Seventy five women with Lynch syndrome or first-degree relatives are offered annual gynecological screening between 2003 and 2012.

  • All (pre)malignant endometrial lesions were found by transvaginal ultrasound.

  • Adding standard endometrial sampling to annual transvaginal ultrasound has no additional value in detection of endometrial lesions.

Abstract

Objective

Based on previous studies, standard gynecological screening consisting of annual transvaginal ultrasonography (TVU) was added with endometrial sampling in women with Lynch syndrome (LS). The aim of this study was to evaluate the additional value of endometrial sampling in detecting (pre)malignancies of the endometrial tissue in women with LS or first-degree relatives.

Methods

All women above 30 years of age with LS or first-degree relatives at 50% risk of LS are offered annual gynecological screening in our family cancer clinic. Endometrial screening results from January 2003-December 2007 (period I: standard screening by transvaginal sonography and serum CA125) were compared with screening results from January 2008-June 2012 (period II: standard screening added with endometrial sampling).

Results

Seventy five women (300 patient years) were screened annually. There were 266 screening visits, 117 in period I and 149 in period II. In period I, four premalignant endometrial lesions were detected and one endometrial carcinoma (FIGO stage IB). In period II, two premalignancies were found. None of the lesions would have been missed without standard endometrial sampling. No interval endometrial cancers were detected in this study.

Conclusion

In this study, annual endometrial screening seems an effective screening tool in the detection of premalignancies and early endometrial cancer in women with LS. Adding standard endometrial sampling to annual TVU has no additional value in the early detection of (pre)malignant endometrial lesions in women with LS in this study.

Introduction

Women with Lynch syndrome (LS), previously called Hereditary Non Polyposis Colorectal Cancer (HNPCC), have an autosomal dominant inherited mutation in one of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2. LS is characterized by a high risk and early occurrence of colorectal cancer and extra colonic cancers [1]. The second most common cancer in female LS patients is endometrial cancer.

The estimated cumulative lifetime risk to develop endometrial cancer in women with LS varies in different reports between 21% and 71%. MLH1 and MSH2 mutation carriers have a lifetime risk up to 60% to develop endometrial cancer; carriers of an MSH6 mutation have a risk up to 71%, [1], [2], [3], [4], [5] although lower risks (24%) have been reported as well [6]. For PMS2 mutation carriers, a risk of 15% has been reported [7]. However, series of PMS2 mutation carriers are significantly smaller than those for the other mismatch repair genes and cancer risk therefore less well established. The overall annual incidence rate of developing endometrial cancer after the age of 40 years in LS is 2,5% [8].

The high risk of endometrial cancer in LS and the earlier age of onset, together with a well-detectable and treatable premalignant or early malignant stage, is the reason to consider endometrial cancer screening in these women and their first degree relatives at 50% risk of LS [1], [2], [9], [10]. A few studies have investigated the optimal gynecological screening protocol in women with LS [1], [4], [11], [12], [13]. Interval endometrial carcinomas occurred with annual screening of TVU alone in two studies [4], [11]. In a study by Renkonen et al., mutation carriers were screened with TVU and standard endometrial sampling of the endometrial tissue at an interval of 2–3 years [1]. In their study, eight of fourteen carcinomas and premalignant lesions were diagnosed by endometrial sampling alone. However, despite endometrial sampling during most of the screening visits in this study, three interval carcinomas occurred. The tumour stage and the survival curve were more optimal in the group of patients who underwent screening than in 83 mutation positive endometrial cancers patients who had not attended screening [1]. In 2009 Gerritzen et al. also found significantly more (pre)malignancies in women with standard endometrial sampling together with annual TVU, than in women with screening by TVU alone [12]. It was concluded that TVU alone is insufficient to detect early endometrial cancer in all cases, especially among premenopausal women, and that adding endometrial sampling improves the effectiveness of gynecological screening in women with LS [1], [12]. Recently Manchandra et al. found four (pre)malignant lesions with TVU and outpatient hysteroscopy with endometrial sampling in 41 women with LS. TVU alone detected two of four lesions [13]. In our hospital, the screening protocol was changed in women with LS or first-degree relatives at 50% risk of carrying the LS mutation and endometrial sampling was added to annual TVU from January 1st 2008. During endometrial sampling, some patients experience painful cramping but data about this symptom are lacking from other studies. Data about effectiveness of annual gynecological screening by TVU in women with LS or first degree relatives in our hospital between 1991 and 2002 have been published by Rijcken et al. [4]. In the current study screening data were analyzed of all women with LS or first degree relatives, who were annually screened between January 2003 and June 2012. The aim of the present study is to evaluate the additional value of endometrial sampling to annual TVU as a standard screening procedure in detecting (pre)malignant endometrial lesions in women with LS or first-degree relatives at 50% risk of carrying the LS mutation.

Section snippets

Setting

Since 1991, a gynecological screening program for females with LS and first-degree relatives at 50% risk of carrying the LS mutation was introduced at the Family Cancer Clinic (FCC) of the University Medical Center Groningen at a recommended age to start of 30 years [14]. In all women with LS, a pathogenic mutation in either MLH1, MSH2, MSH6 or PMS2 had been detected using methods published previously [15], [16], [17]. All clinical data from LS carriers and first-degree relatives at 50% risk of

Results

From 2003 to 2012, 61 women were premenopausal and 14 were postmenopausal. The median age at the first gynecological screening was 38 years (range 26–61) and 41 years (range 23–67 years) in periods I and II, respectively. However three women (23–26–26 years of age) received information about the screening program starting from age 30, and asked to be screened during the first visit. At that visit standard gynaecological screening was performed. Two 26 year old women returned for screening according

Discussion

In this study in 75 women, (300 patient years) there was no additional value of endometrial sampling in the early detection of endometrial cancer in women with Lynch syndrome or their first-degree relatives at 50% risk of carrying the LS mutation. There were 266 standard screening visits. In period I (2003–2007), in 117 screening visits, four premalignant endometrial lesions were detected and one endometrial carcinoma (FIGO stage IB). In period II (2008–2012), in 149 screening visits, two

Conflict of Interest Statement

The authors declare that there are no conflicts of interest.

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