Evaluation of Ki67 expression across distinct categories of breast cancer specimens: a population-based study of matched surgical specimens, core needle biopsies and tissue microarrays.
BACKGROUND
Tumor cell proliferation in breast cancer is strongly prognostic and may also predict response to chemotherapy. However, there is no consensus on counting areas or cut-off values for patient stratification. Our aim was to assess the matched level of proliferation by Ki67 when using different tissue categories (whole sections, WS; core needle biopsies, CNB; tissue microarrays, TMA), and the corresponding prognostic value.


METHODS
We examined a retrospective, population-based series of breast cancer (n = 534) from the Norwegian Breast Cancer Screening Program. The percentage of Ki67 positive nuclei was evaluated by visual counting on WS (n = 534), CNB (n = 154) and TMA (n = 459).


RESULTS
The median percentage of Ki67 expression was 18% on WS (hot-spot areas), 13% on CNB, and 7% on TMA, and this difference was statistically significant in paired cases. Increased Ki67 expression by all evaluation methods was associated with aggressive tumor features (large tumor diameter, high histologic grade, ER negativity) and reduced patient survival.


CONCLUSIONS
There is a significant difference in tumor cell proliferation by Ki67 across different sample categories. Ki67 is prognostic over a wide range of cut-off points and for different sample types, although Ki67 results derived from TMA sections are lower compared with those obtained using specimens from a clinical setting. Our findings indicate that specimen specific cut-off values should be applied for practical use.
Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Gøril
G
Knutsvik
Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Ingunn M
IM
Stefansson
Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Sura
S
Aziz
Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Jarle
J
Arnes
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Johan
J
Eide
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Karin
K
Collett
Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
Lars A
LA
Akslen
D000368:Aged; D062005:Biopsy, Large-Core Needle; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D046888:Tissue Array Analysis
D019394:Ki-67 Antigen