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Extensive apoptosis in ductal carcinoma in situ of the breast
Author(s) -
Bodis Stephan,
Siziopikou Kalliopi P.,
Schnitt Stuart J.,
Harris Jay R.,
Fisher David E.
Publication year - 1996
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19960501)77:9<1831::aid-cncr11>3.0.co;2-0
Subject(s) - apoptosis , necrosis , ductal carcinoma , tunel assay , programmed cell death , pathology , fragmentation (computing) , dna fragmentation , medicine , immunohistochemistry , cancer research , carcinoma in situ , biology , breast cancer , carcinoma , cancer , ecology , biochemistry
BACKGROUND More than 50% of breast ductal carcinomas in situ (DCIS) contain significant histologic necrosis, an important prognostic factor for determining recurrence and progression to invasive breast cancer. We have examined whether the mechanism of this spontaneous cell death might be apoptosis, a genetically encoded suicide pathway that may be triggered by various events including dysregulated cell proliferation. METHODS Twenty‐five untreated DCIS cases accessioned at our institution were examined for subtype, grade, and presence of apoptosis using two criteria: (1) cellular morphology (shrinkage, nuclear condensation, fragmentation, apoptotic bodies, and lack of inflammatory component); and (2) terminal transferase (TUNEL) staining of DNA fragmentation, a characteristic though less specific feature of apoptosis. Immunohistochemical staining was also carried out to assess whether wild‐type p53, a regulator of apoptosis, was associated with this cell death. RESULTS In all 19 cases with intraductal necrosis, cellular morphology was consistent with apoptotic death, despite its presence within sheets of “geographic necrosis.” Additionally, the identical regions were all strongly TUNEL‐positive. No evidence of TUNEL staining was seen in 5 Grade I DCIS cases without intraductal necrosis. Immunohistochemical staining suggested that this apoptosis was independent of p53 mutational status. CONCLUSIONS Extensive intraductal necrosis in DCIS is likely to represent apoptosis. However, it is unlikely that this apoptosis is regulated by p53. The apparently abundant apoptosis identified here, particularly in high grade DCIS, may be important in explaining why spontaneous cell death in DCIS is associated with a worse prognosis. Cancer 1996;77:1831‐5.