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Heo, Park, Lee, Lee, and Kim: A Case of Perimenopausal Endometrial Cancer in a Woman with MSH2 Germline Mutation
Case Report

Journal of Menopausal Medicine 2013; 19(3): 143-146.

Published online: 27 December 2013

DOI: https://doi.org/10.6118/jmm.2013.19.3.143

A Case of Perimenopausal Endometrial Cancer in a Woman with MSH2 Germline Mutation

Eun Jin Heo, M.D.1, Jung Min Park, M.D.1, Eun Hee Lee, M.D.2, Hyoun Wook Lee, M.D.2, Min Kyu Kim, M.D.3

1Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

2Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.

3Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.

Address for Correspondence: Min Kyu Kim, Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, 50 Hasung-dong, Masan Hoewon, Changwon 630-723, Korea. Tel: +82-55-290-6040, Fax: +82-2-6442-9285, minkyukim@skku.edu

Received 15 August 2013       Revised 18 September 2013       Accepted 18 September 2013

Copyright © 2013 by The Korean Society of Menopause

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

Abstract

Lynch syndrome is a genetic malignancy syndrome affecting the colon, endometrium, and other organs. It is difficult to find a Lynch syndrome patient without any family history of cancer. We have recently examined an endometrial cancer patient with a MSH2 gene mutation without a family history of cancer. A 55-year old Korean woman was admitted to a local clinic for vaginal bleeding. An endometrial biopsy revealed the presence of adenocarcinoma (endometrioid type, grade 1). After surgical staging, no further adjuvant therapy was required. Analysis of the tissue using immunohistochemistry (IHC) showed the endometrium stained negatively for MSH2. Microsatellite instability (MSI) was analyzed for five markers. The patient was scored as unstable. Further, additional gene sequencing revealed one missense mutation in c.23C > T (p.Thr8Met). This is the first case of Lynch syndrome endometrial cancer in Korea in which the patient does not have any family history of cancer.

Keywords: Endometrial neoplasms, Lynch syndrome

Introduction

Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer [HNPCC]) results from mutations in mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) and is associated with a variety of extra-colonic sites, like endometrium, stomach, ovaries, urinary tract and kidneys, biliary tract, pancreas, small intestine, brain and skin.1 Endometrial cancer is the most common malignant disorder observed after HNPCC.
Considering that Lynch syndrome is an autosomal-dominant inherited cancer syndrome, identifying a family history using genetic counseling can lead to further tests based on the current guidelines (revised Amsterdam2 or Bethesda3 criteria). And identification of individuals who have increased risk of occurring hereditary cancers would enable screening and early detection of cancer, which may reduce disease-specific mortality. Recording a patient's family history is the first step in the work-up of Lynch syndrome patients. However, recording an accurate family history is often neglected or inconsistent.4,5 It can be challenging to advise patients to proceed with additional testing when they do not have a family history of cancer.
Screening for colorectal cancer in HNPCC has been proven to improve survival and the cost-effectiveness of treatments, but the benefits of screening for gynecological cancers in Lynch syndrome patients have not yet been proven. Additionally, there is no consensus regarding the optimal screening tests to perform based on country or patient ethnicity.
Here, we present a case of endometrial cancer in a Lynch syndrome patient that did not have a family history of cancer.

Case Report

A 55-year-old Korean woman was admitted to a local clinic for vaginal bleeding. An endometrial biopsy revealed the presence of adenocarcinoma (endometrioid type, grade 1). The patient was referred to Samsung Changwon Hospital for further evaluation and treatment. The patient received pelvic magnetic resonance imaging, computed tomography scan, and other diagnostic tests. The patient had a cancer antigen 125 (CA 125) level of 9.06 U/mL and no other abnormal masses were visible in imaging tests. Complete surgical staging including total hysterectomy, bilateral salpingo-oophorectomy, washing cytology, and pelvic lymph node dissection was performed. The operation was concluded after confirming a frozen biopsy of the pelvic lymph node was not cancerous.
Although this patient had no family history of cancer (her three sisters and parents were alive without any cancer diagnoses at the time of counseling), screening immunohistochemistry (IHC; MLH1, MSH2) was performed due to the genetic risk of Lynch syndrome. The results indicated that MLH1 was positive in 90% f the sample and MSH2 was negative (Fig. 1). The tissue pathology reported the tumor stage was IA and adjuvant treatment was not recommended.
According to diagnostic algorithms and after genetic counseling, microsatellite instability (MSI) and gene sequencing were performed. MSI was analyzed for five markers (BAT25, BAT26, D2S123, D5S346, and D17S250). The results indicate there were two unstable markers (BAT25 and BAT26), and the patient was scored MSI-high (unstable). Further gene sequencing analyses revealed one missense mutation (c.23C > T [p.Thr8Met]) (Fig. 2). Therefore, a gastroenterologist was involved in the patient's counseling. A screening endoscopy was performed and the results were normal.

Discussion

This case demonstrates that Lynch syndrome-related cancer can occur in a patient despite the lack of any family history. This is the first case report of an endometrial cancer patient with a Lynch syndrome germline mutation without family history in Korea.
The risk of developing a second cancer is approximately 25% after 10 years and 50% after 15 years following the initial diagnosis of Lynch syndrome.6 Therefore, the patient and her family were offered cancer screening and genetic counseling.
Approximately 2% to 5% of endometrial cancers may be caused by an inherited susceptibility.7 In Lynch syndrome carriers, the lifetime risk of endometrial cancer has been estimated to be 42 to 54%, and may equal or exceed the risk of colorectal cancer.8
Lynch syndrome is caused by a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, and PMS2), and accounts for the majority of inherited cases.7
In younger patients, the incidence of endometrial cancer increases to 9% and better survival rates.9,10
Information on family history is important for identifying individuals that could benefit from genetic counseling and predictive genetic testing. However, other genetic screening tests are effective in selecting suitable patients. The results from this patient's test (IHC and MSI) were abnormal. After counseling and describing the risk and benefits obtained from these results, further confirmative tests for detection of a pathogenic mutation in one of the DNA mismatch repair genes were performed with the patient's permission.
With the advances in molecular biology now available for the diagnosis of genetic cancers, clinicians can help prevent these cancers by counseling patients and prescribing adequate and appropriate tests.
In known mutation carriers without any colorectal adenomas, screening colonoscopy appears to be the most reasonable choice.11 However, prophylactic subtotal colectomy remains an option for patients who have significant anxiety about cancer risk or concern about the safety of repeated colonoscopies. Additionally, colectomy can be used if the patient is unable to receive periodic surveillance colonoscopies.12
More information is required to determine the appropriate genetic tests for counseling and prevention according to the country and ethnicity of the patient.
It is also important to identify patients with Lynch syndrome because families of mutation carriers may benefit from genetic counseling, testing, and intensified cancer surveillance.
In conclusion, gynecological oncologists should provide information of the genetic cancer risk to endometrial cancer patients in an effort to prevent second cancers in patients and family with Lynch syndrome. Patients should undergo the correct genetic tests and should be counseled appropriately, which is important for reducing cancer mortality and costs.

Figures and Tables

Fig. 1
Immunohistochemistry results (× 200).
jmm-19-143-g001
Fig. 2
Gene sequencing result.
jmm-19-143-g002

References

1. Ladabaum U, Ford JM. Lynch syndrome in patients with colorectal cancer: finding the needle in the haystack. JAMA. 2012; 308:1581–1583.
2. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999; 116:1453–1456.
3. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004; 96:261–268.
4. Foo W, Young JM, Solomon MJ, Wright CM. Family history? The forgotten question in high-risk colorectal cancer patients. Colorectal Dis. 2009; 11:450–455.
5. Kelly PP. Colorectal cancer family history assessment. Clin J Oncol Nurs. 2011; 15:E75–E82.
6. Lynch HT, Harris RE, Lynch PM, Guirgis HA, Lynch JF, Bardawil WA. Role of heredity in multiple primary cancer. Cancer. 1977; 40:4 Suppl. 1849–1854.
7. Meyer LA, Broaddus RR, Lu KH. Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer Control. 2009; 16:14–22.
8. Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999; 81:214–218.
9. Berends MJ, Wu Y, Sijmons RH, van der Sluis T, Ek WB, Ligtenberg MJ, et al. Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis. J Clin Oncol. 2003; 21:4364–4370.
10. Lu KH, Schorge JO, Rodabaugh KJ, Daniels MS, Sun CC, Soliman PT, et al. Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer. J Clin Oncol. 2007; 25:5158–5164.
11. Lindor NM, Petersen GM, Hadley DW, Kinney AY, Miesfeldt S, Lu KH, et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA. 2006; 296:1507–1517.
12. Vasen HF, Moslein G, Alonso A, Bernstein I, Bertario L, Blanco I, et al. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet. 2007; 44:353–362.
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