Elsevier

Gynecologic Oncology

Volume 150, Issue 2, August 2018, Pages 324-330
Gynecologic Oncology

Characteristics of Lynch syndrome associated ovarian cancer

https://doi.org/10.1016/j.ygyno.2018.03.060Get rights and content

Highlights

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    Ovarian cancer in women with LS develops at an early age, with a wide age-range of onset and at an early stage.

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    These LS associated ovarian cancers most often has an endometrioid or serous type histology with a good overall survival.

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    The early stage of ovarian cancer, in women with LS, could not be attributed to annual gynecological surveillance.

Abstract

Objective

To describe clinical characteristics of Lynch syndrome associated ovarian cancer and the efficacy of surveillance in the early detection of these ovarian cancers.

Methods

All Lynch syndrome associated ovarian cancer cases identified in either the Dutch Lynch syndrome registry (DLSR) between 1987 and 2016, and/or the cohort at the University Medical Center Groningen (UMCG) between 1993 and 2016 were included. Clinical data on age at diagnosis, mutation type, histological type, FIGO stage, treatment, follow-up and gynecological surveillance were collected.

Results

A total of 46/798 (6%) women in the DLSR and 7/80 (9%) in the UMCG cohort were identified as LS associated ovarian cancer patients. The median age at ovarian cancer diagnosis was 46.0 years (range 20–75 years). The most frequently reported histological type was endometrioid adenocarcinoma (40%; n = 21) and serous carcinoma (36%; n = 19). Most tumors (87%; n = 46) were detected at an early stage (FIGO I/II). Forty-one of 53 (77%) patients were diagnosed with ovarian cancer before LS was diagnosed. In the other 12/53 (23%) women, ovarian cancer developed after starting annual gynecological surveillance for LS; three ovarian cancers were screen-detected in asymptomatic women. Overall survival was 83%.

Conclusion

Ovarian cancer in women with LS has a wide age-range of onset, is usually diagnosed at an early stage with predominantly endometrioid type histology and a good overall survival. The early stage at diagnosis could not be attributed to annual gynecological surveillance.

Introduction

Hereditary predisposition accounts for approximately 5% of endometrial cancers and up to 24% of epithelial ovarian cancers [1,2]. LS is an autosomal dominant tumor syndrome, caused by a germline mutation in one of the DNA mismatch repair (MMR) genes, which, after a loss of function mutation of the normal allele, leads to microsatellite instability (MSI) and increased cancer risk. It accounts for most inherited endometrial cancers and a minority of inherited ovarian cancers, whereas a germline mutation in a BRCA1 or BRCA2 gene accounts for most inherited ovarian cancers [[3], [4], [5], [6]]. In women with LS, endometrial cancer is after colon cancer the most common tumor type, [7,8] with a cumulative lifetime risk of 15–60% and a mean age at diagnosis of 55–60 years, (range 30–80 years) depending on which gene is mutated [7,[9], [10], [11]]. The cumulative lifetime risk of ovarian cancer in LS varies between 6 and 12% with a reported mean age at diagnosis of around 45 years [7,[11], [12], [13], [14], [15]]. Endometrial surveillance by transvaginal ultrasound and endometrial sampling can be effective in diagnosing endometrial cancer at a pre-invasive or early stage [9,16,17]. The value of surveillance for ovarian cancer in LS has never been established and is under debate [9,14,18]. Ovarian cancer surveillance has not been proven effective in the general population and among women with a BRCA1/2 gene mutation [[19], [20], [21], [22], [23], [24]]. Most sporadic and BRCA-associated ovarian cancers are diagnosed at an advanced stage and interval ovarian cancers can present shortly after surveillance visits. In only a few surveillance studies a small number of women with LS are included, the information about clinical and histopathological characteristics of ovarian cancer in women with LS is therefore scattered and unclear [15,[25], [26], [27]].

The aim of this study was to analyze the clinical and histopathological characteristics of LS associated ovarian cancer and to investigate the role of surveillance in the early detection of these ovarian cancers.

Section snippets

Materials and methods

For this study, data of two prospective cohorts of ovarian cancer patients were used. The first cohort was derived from the Dutch Lynch Syndrome Registry (DLSR) between 1987 and 2016. The second cohort was from the Family Cancer Clinic at the University Medical Center Groningen (UMCG) between 1993 and 2016. The DLSR was started in 1987 and embedded in The Netherlands Foundation for the detection of Hereditary Tumors, which was established in 1985 [28]. Data managers of the Netherlands

Results

The DLSR contained 798 female LS carriers. The mean age of this cohort was 58 years with a median age of 58 years (range 23–98 years), at time of study entry. In this registry 241 (30%) women were carrier of a MLH1 gene mutation, 276 (35%) of a MSH2, 237 (30%) of a MSH6, 41 (5%) had a PMS2 gene mutation and for three women, (who were included in the early days from families fulfilling the Amsterdam criteria) the type of mutation was not recorded. (Table 1) The cohort of the UMCG consists of 80

Discussion

This study included 53 LS associated ovarian cancer patients which is one of the largest reported cohort. The mean and median age of the ovarian cancer diagnosis was 46 years, with a wide age range of 20–75 years. A total of 25% of the women were under 40 years of age at diagnosis of LS associated ovarian cancer. Histopathological presentation was most often an endometrioid or serous type and most ovarian cancers were diagnosed at an early stage (87% FIGO stage I/II) with a relatively good five

Conflict of interest statement

All authors declare that there are no conflicts of interest.

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