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Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases

Johanna E Lotsari1*, Annette Gylling1, Wael M Abdel-Rahman12, Taina T Nieminen1, Kristiina Aittomäki3, Marjukka Friman4, Reino Pitkänen4, Markku Aarnio5, Heikki J Järvinen6, Jukka-Pekka Mecklin5, Teijo Kuopio4 and Päivi Peltomäki1

Author Affiliations

1 Department of Medical Genetics, Biomedicum Helsinki, P.O.Box 63 (Haartmaninkatu 8), University of Helsinki, Helsinki, Finland, FIN-00014

2 College of Health Sciences, University of Sharjah, P.O. 27272 Sharjah, United Arab Emirates

3 Department of Clinical Genetics, Helsinki University Central Hospital, P.O. Box 160 (Meilahdentie 2), Helsinki, Finland, FIN-00029

4 Department of Pathology, Jyväskylä Central Hospital, (Keskussairaalantie 19), Jyväskylä, Finland, FIN-40620

5 Department of Surgery, Jyväskylä Central Hospital, (Keskussairaalantie 19), Jyväskylä, Finland, FIN-40620

6 Department of Surgery, Helsinki University Central Hospital, P.O Box 340 (Haartmaninkatu 4), Helsinki, Finland, FIN-00029

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Breast Cancer Research 2012, 14:R90  doi:10.1186/bcr3205

See related editorial by Ford,

Published: 12 June 2012



Breast carcinoma is the most common cancer in women, but its incidence is not increased in Lynch syndrome (LS) and studies on DNA mismatch repair deficiency (MMR) in LS-associated breast cancers have arrived at conflicting results. This study aimed to settle the question as to whether breast carcinoma belongs to the LS tumor spectrum.


MMR status and epigenetic profiles were determined for all available breast carcinomas identified among 200 LS families from a nation-wide registry (23 tumors from mutation carriers and 18 from non-carriers). Sporadic breast carcinomas (n = 49) and other cancers (n = 105) from MMR gene mutation carriers were studied for comparison.


The proportion of breast carcinomas that were MMR-deficient based on absent MMR protein, presence of microsatellite instability, or both was significantly (P = 0.00016) higher among breast carcinomas from mutation carriers (13/20, 65%) compared to non-carriers (0/14, 0%). While the average age at breast carcinoma diagnosis was similar in carriers (56 years) and non-carriers (54 years), it was lower for MMR-deficient versus proficient tumors in mutation carriers (53 years versus 61 years, P = 0.027). Among mutation carriers, absent MMR protein was less frequent in breast carcinoma (65%) than in any of seven other tumor types studied (75% to 100%). Tumor suppressor promoter methylation patterns were organ-specific and similar between breast carcinomas from mutation carriers and non-carriers.


Breast carcinoma from MMR gene mutation carriers resembles common breast carcinoma in many respects (for example, general clinicopathological and epigenetic profiles). MMR status makes a distinction: over half are MMR-deficient typical of LS spectrum tumors, while the remaining subset which is MMR-proficient may develop differently. The results are important for appropriate surveillance in mutation carriers and may be relevant for LS diagnosis in selected cases.