Comparison of loss heterozygosity in primary and recurrent ductal carcinoma in situ of the breast.
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.
Lininger
R A
RA
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Fujii
H
H
Man
Y G
YG
Gabrielson
E
E
Tavassoli
F A
FA
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm