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 Brian Jenkins

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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
Volume107
Issue number4
DOIs
StatePublished - Nov 20 2003

Fingerprint

Microsatellite Instability
DNA Mismatch Repair
Breast Neoplasms
Carcinoma, Intraductal, Noninfiltrating
Mutation
Microdissection
Medullary Carcinoma
Tetraploidy
Ploidies
DNA
Neoplasms
Lasers
Immunohistochemistry
Antibodies
Genes
Familial Breast Cancer

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Microsatellite instability in hereditary and sporadic breast cancers. / Adem, Camilo; Soderberg, Cheryl L.; Cunningham, Julie M; Reynolds, Carol; Sebo, Thomas J.; Thibodeau, Stephen N; Hartmann, Lynn C.; Jenkins, Robert Brian.

In: International Journal of Cancer, Vol. 107, No. 4, 20.11.2003, p. 580-582.

Research output: Contribution to journalArticle

Adem, Camilo ; Soderberg, Cheryl L. ; Cunningham, Julie M ; Reynolds, Carol ; Sebo, Thomas J. ; Thibodeau, Stephen N ; Hartmann, Lynn C. ; Jenkins, Robert Brian. / Microsatellite instability in hereditary and sporadic breast cancers. In: International Journal of Cancer. 2003 ; Vol. 107, No. 4. pp. 580-582.
@article{9a80f4bcbe5249bb8dabc73c7cb005ee,
title = "Microsatellite instability in hereditary and sporadic breast cancers",
abstract = "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.",
keywords = "BRCA1/2, Genetic instability, HMLH1, HMSH2, Medullary carcinoma",
author = "Camilo Adem and Soderberg, {Cheryl L.} and Cunningham, {Julie M} and Carol Reynolds and Sebo, {Thomas J.} and Thibodeau, {Stephen N} and Hartmann, {Lynn C.} and Jenkins, {Robert Brian}",
year = "2003",
month = "11",
day = "20",
doi = "10.1002/ijc.11442",
language = "English (US)",
volume = "107",
pages = "580--582",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Microsatellite instability in hereditary and sporadic breast cancers

AU - Adem, Camilo

AU - Soderberg, Cheryl L.

AU - Cunningham, Julie M

AU - Reynolds, Carol

AU - Sebo, Thomas J.

AU - Thibodeau, Stephen N

AU - Hartmann, Lynn C.

AU - Jenkins, Robert Brian

PY - 2003/11/20

Y1 - 2003/11/20

N2 - 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.

AB - 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.

KW - BRCA1/2

KW - Genetic instability

KW - HMLH1

KW - HMSH2

KW - Medullary carcinoma

UR - http://www.scopus.com/inward/record.url?scp=0142021895&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142021895&partnerID=8YFLogxK

U2 - 10.1002/ijc.11442

DO - 10.1002/ijc.11442

M3 - Article

C2 - 14520695

AN - SCOPUS:0142021895

VL - 107

SP - 580

EP - 582

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 4

ER -