Identification of biomarkers in ductal carcinoma in situ of the breast with microinvasion.
BACKGROUND
Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness.


METHODS
In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method.


RESULTS
There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of necrosis and positive expression ratio of survivin and Bax were significantly higher in DCIS-Mi than in DCIS. In addition, apoptotic index, Ki-67 index, and positive Bcl-2 immunolabeling tended to be higher in DCIS-Mi than in DCIS. Multivariate analysis revealed that the presence of necrosis and positive survivin expression were independent factors associated with invasion.


CONCLUSIONS
Compared with DCIS, DCIS-Mi is characterized by a slightly elevated cell proliferation capacity and enhanced apoptosis within the intraductal lesion, both of which are thought to promote the formation of cell necrotic foci. Furthermore, the differential expression of survivin may serve in deciding the response to therapy and may have some prognostic significance.
Okumura
Yasuhiro
Y
Department of Breast and Endocrine Surgery, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan. sigeoku@yahoo.co.jp
Yamamoto
Yutaka
Y
Zhang
Zhenhuan
Z
Toyama
Tatsuya
T
Kawasoe
Teru
T
Ibusuki
Mutsuko
M
Honda
Yumi
Y
Iyama
Ken-ichi
K
Yamashita
Hiroko
H
Iwase
Hirotaka
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry* / Q000473:pathology*; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D018709:Statistics, Nonparametric
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone