Microsatellite instability in hereditary and sporadic breast cancers

Camilo Adem, Cheryl L. Soderberg, Julie M. Cunningham, Carol Reynolds, Thomas J. Sebo, Stephen N. Thibodeau, Lynn C. Hartmann, Robert B. Jenkins

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Sporadic cancers and familial breast cancers are characterized by an increase in genetic instability. Little is known about whether mismatch repair defects accompany this genetic instability. We investigated invasive and/or in situ breast cancers from 30 women with deleterious BRCA1/2 mutations and unclassified variant BRCA1/2 alterations. Forty cases of sporadic breast cancers were also investigated, including 7 medullary carcinomas. Malignant and benign lesions were examined from all cases to better understand tumor progression. Automated immunohistochemistry, with antibodies directed against hMLH1 and hMSH2, was used to screen cases for possible mismatch repair defects. When loss of expression was noted, DNA ploidy was performed by cytomorphometry. DNA, after laser microdissection, was extracted from a majority of familial cases and their corresponding controls, and microsatellite instability analysis was performed. None of the familial or sporadic cases had loss of hMSH2 expression. All but one lesion, a DCIS arising in a deleterious BRCA2 mutation carrier, had loss of hMLH1 expression and a tetraploid profile by image cytomorphometry. There was no MSI in any explored lesions (n = 34), as determined by molecular analysis, including the DCIS with loss of hMLH1 expression. We conclude that DNA mismatch repair defects involving hMLH1 and hMSH2 underexpression are extremely rare events in sporadic and familial breast cancer. Mismatch repair gene mutations may be secondary random events in breast cancer progression.

Original languageEnglish (US)
Pages (from-to)580-582
Number of pages3
JournalInternational Journal of Cancer
Issue number4
StatePublished - Nov 20 2003


  • BRCA1/2
  • Genetic instability
  • HMLH1
  • HMSH2
  • Medullary carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Microsatellite instability in hereditary and sporadic breast cancers'. Together they form a unique fingerprint.

Cite this