Comparison of loss of heterozygosity in primary and recurrent ductal carcinoma in situ of the breast

Ruth A. Lininger, Hiroaki Fujii, Yan Gao Man, Edward Gabrielson, Fattaneh A. Tavassoli

Research output: Contribution to journalArticle

Abstract

Ductal carcinoma in situ (DCIS) of the breast is often an indolent disease, although some cases are reported to recur many years after a limited surgical resection. It is not known whether these recurrences reflect a resurgence of residual disease or an independent development of a second tumor in susceptible individuals. Therefore, we conducted a longitudinal molecular study of four women with reappearance of DCIS 2 to 15 years after an initial conservative resection. Loss of heterozygosity (LOH) was characterized in both tumors in each case, using several polymerase chain reaction-amplified microsatellite markers on five chromosomal arms commonly affected in breast cancer. In three cases with ipsilateral recurrent disease, all of the allelic losses seen in the initial tumors were also seen in the recurrent lesions, suggesting a common genetic pathway for the development of both lesions and continuous proliferation of residual disease. The presence of at least one additional LOH in all of the three recurrent tumors, however, suggests that the recurrent tumors developed after genetic progression. In contrast, in one case of DCIS that was followed by the development of DCIS in the contralateral breast 7 years later (a case of bilateral DCIS), unrelated LOH patterns were present in the two lesions. These findings suggest that the reappearance of DCIS in the same breast is most commonly the result of a tumor derived from (but not identical to) the original lesion, with acquisition of additional genetic changes, even when the recurrent lesion manifested itself many years (15 years, in one case) after the initial presentation. Furthermore, genetic progression could be detected in tumors recurring in as little as 2 years after the initial resection.

Original languageEnglish (US)
Pages (from-to)1151-1159
Number of pages9
JournalModern Pathology
Volume11
Issue number12
StatePublished - Dec 1998

Fingerprint

Carcinoma, Intraductal, Noninfiltrating
Loss of Heterozygosity
Breast
Neoplasms
Microsatellite Repeats
Longitudinal Studies
Arm
Breast Neoplasms
Recurrence
Polymerase Chain Reaction

Keywords

  • Biomarkers
  • Breast
  • Genetics
  • Neoplasms
  • Recurrence

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Lininger, R. A., Fujii, H., Man, Y. G., Gabrielson, E., & Tavassoli, F. A. (1998). Comparison of loss of heterozygosity in primary and recurrent ductal carcinoma in situ of the breast. Modern Pathology, 11(12), 1151-1159.

Comparison of loss of heterozygosity in primary and recurrent ductal carcinoma in situ of the breast. / Lininger, Ruth A.; Fujii, Hiroaki; Man, Yan Gao; Gabrielson, Edward; Tavassoli, Fattaneh A.

In: Modern Pathology, Vol. 11, No. 12, 12.1998, p. 1151-1159.

Research output: Contribution to journalArticle

Lininger, RA, Fujii, H, Man, YG, Gabrielson, E & Tavassoli, FA 1998, 'Comparison of loss of heterozygosity in primary and recurrent ductal carcinoma in situ of the breast', Modern Pathology, vol. 11, no. 12, pp. 1151-1159.
Lininger, Ruth A. ; Fujii, Hiroaki ; Man, Yan Gao ; Gabrielson, Edward ; Tavassoli, Fattaneh A. / Comparison of loss of heterozygosity in primary and recurrent ductal carcinoma in situ of the breast. In: Modern Pathology. 1998 ; Vol. 11, No. 12. pp. 1151-1159.
@article{bcb866f39ea24e8a9d5601407a20b1f6,
title = "Comparison of loss of heterozygosity in primary and recurrent ductal carcinoma in situ of the breast",
abstract = "Ductal carcinoma in situ (DCIS) of the breast is often an indolent disease, although some cases are reported to recur many years after a limited surgical resection. It is not known whether these recurrences reflect a resurgence of residual disease or an independent development of a second tumor in susceptible individuals. Therefore, we conducted a longitudinal molecular study of four women with reappearance of DCIS 2 to 15 years after an initial conservative resection. Loss of heterozygosity (LOH) was characterized in both tumors in each case, using several polymerase chain reaction-amplified microsatellite markers on five chromosomal arms commonly affected in breast cancer. In three cases with ipsilateral recurrent disease, all of the allelic losses seen in the initial tumors were also seen in the recurrent lesions, suggesting a common genetic pathway for the development of both lesions and continuous proliferation of residual disease. The presence of at least one additional LOH in all of the three recurrent tumors, however, suggests that the recurrent tumors developed after genetic progression. In contrast, in one case of DCIS that was followed by the development of DCIS in the contralateral breast 7 years later (a case of bilateral DCIS), unrelated LOH patterns were present in the two lesions. These findings suggest that the reappearance of DCIS in the same breast is most commonly the result of a tumor derived from (but not identical to) the original lesion, with acquisition of additional genetic changes, even when the recurrent lesion manifested itself many years (15 years, in one case) after the initial presentation. Furthermore, genetic progression could be detected in tumors recurring in as little as 2 years after the initial resection.",
keywords = "Biomarkers, Breast, Genetics, Neoplasms, Recurrence",
author = "Lininger, {Ruth A.} and Hiroaki Fujii and Man, {Yan Gao} and Edward Gabrielson and Tavassoli, {Fattaneh A.}",
year = "1998",
month = "12",
language = "English (US)",
volume = "11",
pages = "1151--1159",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Comparison of loss of heterozygosity in primary and recurrent ductal carcinoma in situ of the breast

AU - Lininger, Ruth A.

AU - Fujii, Hiroaki

AU - Man, Yan Gao

AU - Gabrielson, Edward

AU - Tavassoli, Fattaneh A.

PY - 1998/12

Y1 - 1998/12

N2 - Ductal carcinoma in situ (DCIS) of the breast is often an indolent disease, although some cases are reported to recur many years after a limited surgical resection. It is not known whether these recurrences reflect a resurgence of residual disease or an independent development of a second tumor in susceptible individuals. Therefore, we conducted a longitudinal molecular study of four women with reappearance of DCIS 2 to 15 years after an initial conservative resection. Loss of heterozygosity (LOH) was characterized in both tumors in each case, using several polymerase chain reaction-amplified microsatellite markers on five chromosomal arms commonly affected in breast cancer. In three cases with ipsilateral recurrent disease, all of the allelic losses seen in the initial tumors were also seen in the recurrent lesions, suggesting a common genetic pathway for the development of both lesions and continuous proliferation of residual disease. The presence of at least one additional LOH in all of the three recurrent tumors, however, suggests that the recurrent tumors developed after genetic progression. In contrast, in one case of DCIS that was followed by the development of DCIS in the contralateral breast 7 years later (a case of bilateral DCIS), unrelated LOH patterns were present in the two lesions. These findings suggest that the reappearance of DCIS in the same breast is most commonly the result of a tumor derived from (but not identical to) the original lesion, with acquisition of additional genetic changes, even when the recurrent lesion manifested itself many years (15 years, in one case) after the initial presentation. Furthermore, genetic progression could be detected in tumors recurring in as little as 2 years after the initial resection.

AB - Ductal carcinoma in situ (DCIS) of the breast is often an indolent disease, although some cases are reported to recur many years after a limited surgical resection. It is not known whether these recurrences reflect a resurgence of residual disease or an independent development of a second tumor in susceptible individuals. Therefore, we conducted a longitudinal molecular study of four women with reappearance of DCIS 2 to 15 years after an initial conservative resection. Loss of heterozygosity (LOH) was characterized in both tumors in each case, using several polymerase chain reaction-amplified microsatellite markers on five chromosomal arms commonly affected in breast cancer. In three cases with ipsilateral recurrent disease, all of the allelic losses seen in the initial tumors were also seen in the recurrent lesions, suggesting a common genetic pathway for the development of both lesions and continuous proliferation of residual disease. The presence of at least one additional LOH in all of the three recurrent tumors, however, suggests that the recurrent tumors developed after genetic progression. In contrast, in one case of DCIS that was followed by the development of DCIS in the contralateral breast 7 years later (a case of bilateral DCIS), unrelated LOH patterns were present in the two lesions. These findings suggest that the reappearance of DCIS in the same breast is most commonly the result of a tumor derived from (but not identical to) the original lesion, with acquisition of additional genetic changes, even when the recurrent lesion manifested itself many years (15 years, in one case) after the initial presentation. Furthermore, genetic progression could be detected in tumors recurring in as little as 2 years after the initial resection.

KW - Biomarkers

KW - Breast

KW - Genetics

KW - Neoplasms

KW - Recurrence

UR - http://www.scopus.com/inward/record.url?scp=0032437875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032437875&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 1151

EP - 1159

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 12

ER -