Case reportBreast cancer in an MSH2 gene mutation carrier
Introduction
The MSH2 gene is coding for one of the mismatch repair enzymes involved in the repair of DNA replication errors. Microsatellites, tandem repeats of 1 to 5 base pairs (bp), are extremely vulnerable for replication errors. As a result, microsatellite instability (MSI) is a hallmark of defective DNA repair. Replication errors in microsatellites will result in an increase or decrease in the length of the tandem repeats that can be detected after DNA amplification. Germline mutations in the MSH2 gene are associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. This syndrome is also associated with mutations in other mismatch repair genes, MLH1, MSH6, PMS2, and rarely PMS1. Carriers of mutations in these mismatch repair genes are at an increased risk for developing colorectal cancer, but also a number of extracolonic cancers. Of these latter, cancer of the endometrium, small bowel, ureter, and pelvis has been included in the clinical criteria for recognition of the HNPCC syndrome [1]. Breast cancer is not included in these clinical criteria, and no increased lifetime risk was reported [1]. We report here a case of breast cancer in an MSH2 gene mutation carrier in which we were able to demonstrate that this mutation was involved in the development of this tumor by loss of the wild-type MSH2 allele.
Section snippets
Case report
A 49-year-old woman reported with a palpable lesion in her right breast. Mammography revealed a density in her right breast, which was thought to be malignant (BI-RAD 5). A carcinoma was diagnosed in a core needle biopsy. A lumpectomy with sentinel lymph node procedure was performed. On histological examination, a 2.1-cm-wide invasive ductal carcinoma, Bloom and Richardson grade 2 with positive staining for estrogen and progesterone receptor, was found. The tumor was remarkable for the presence
Results
The tumor cells showed strong cytoplasmic expression of cytokeratin 8/18 (Fig. 1).
Immunohistochemistry for mismatch repair protein expression demonstrated absence of expression of MSH2 and MSH6 in the tumor cell nuclei, whereas normal cells showed nuclear expression of these proteins. MLH1 and PMS2 were expressed both in nuclei of the tumor cells and normal cells (Fig. 1).
The MSI analysis revealed unequivocally an MSI pattern for the mononucleotide repeat markers Bat25, Bat26, and Bat40.
Discussion
Breast cancer is not included in the clinical criteria for the recognition of patients with the HNPCC syndrome [1]. The MSI phenotype is rare in unselected breast cancers [2]. In a study of MSI in patients that presented with synchronous or metachronous breast and colorectal cancer, no MSI was found in the breast cancers [3]. Breast cancer with an MSI-high pattern has been reported in the Dutch HNPCC register [4], [5]. In this register, breast cancer was found in 5 patients with MLH1 germline
References (15)
- et al.
New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC
Gastroenterology
(1999) - et al.
Hereditary nonpolyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds
Am J Hum Genet
(2001) - et al.
Tumour biological features of BRCA1-induced breast and ovarian cancer
Eur J Cancer
(1997) - et al.
Microsatellite instability is uncommon in breast cancer
Clin Cancer Res
(1999) - et al.
Exclusion of breast cancer as an integral tumor of hereditary nonpolyposis colorectal cancer
Cancer Res
(2002) - et al.
Is breast cancer part of the tumor spectrum of hereditary nonpolyposis colorectal cancer?
Am J Hum Genet
(2001) - et al.
Correspondence re: Muller A et al, Exclusion of breast cancer as an integral tumor of hereditary nonpolyposis colorectal cancer
Cancer Res
(2003)
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