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Comparative Study
. 2010 Aug;57(2):212-9.
doi: 10.1111/j.1365-2559.2010.03620.x.

Histological grading of breast cancer on needle core biopsy: the role of immunohistochemical assessment of proliferation

T'ng Chang Kwok  1 , Emad A Rakha, Andrew H S Lee, Matthew Grainge, Andrew R Green, Ian O Ellis, Desmond G Powe
Affiliations
Free PMC article
Comparative Study

Histological grading of breast cancer on needle core biopsy: the role of immunohistochemical assessment of proliferation

T'ng Chang Kwok et al. Histopathology. 2010 Aug.
Free PMC article

Abstract

Aims: Histological grade assessed on needle core biopsy (NCB) moderately concurs with the grade in the surgical excision specimen (SES) (kappa-values between 0.35 and 0.65). A major cause of the discrepancy is underestimation of mitoses in the NCB specimen. The aim was to determine the best method of assessing proliferation on NCB.

Methods and results: Proliferative activity of 101 invasive carcinomas of the breast on NCB and SES was assessed using mitotic counts on routine haematoxylin and eosin (H&E) sections and immunohistochemical markers Mib-1 and phosphorylated histone H3 (PPH3). H&E mitotic count in SES was considered as the gold standard. H&E mitotic count was found to be underestimated on NCB when compared with that in SES (P < 0.001), but no significant difference was detected between NCB and SES regarding Mib-1 (P = 0.13) or PPH3 (P = 0.073). Using receiver-operating characteristic curve, Mib-1 on NCB was found to agree with the gold standard significantly better than routine H&E on NCB.

Conclusions: Immunohistochemical markers in NCB showed better concordance with H&E mitotic count in SES (gold standard) than routine H&E mitotic count in NCB. Further refinement of cut-offs and scoring methods is needed.

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Figures

Figure 1
Figure 1
Photomicrographs showing PPH3 stained bona fide (A) and non-mitotic figures (B) (P, Prophase; M, Metaphase; A, Anaphase; T, Telophase; Tri, Tripolar mitotic figure; F, fine granular staining; N, intact nuclear membrane).
Figure 2
Figure 2
Photomicrographs showing a wide variation in intensity of Mib-1 nuclear staining pattern in a case with moderate (A) and high (B) Mib-1 growth fraction.
Figure 3
Figure 3
Scatter plots with line of equality showing intra-observer reproducibility of Mib-1 (A) and PPH3 (B) scoring. (MF, Mitotic figures; HPF, high power field).
Figure 4
Figure 4
Scatter plots with line of equality showing H&E mitotic count (A), Mib-1 growth fraction (B) and PPH3 mitotic count (C) in needle core biopsy and surgical excision specimens for the 101 cases in the study.
Figure 5
Figure 5
ROC analysis assessing concordance between NCB proliferation measures (H&E, Mib-1 and PPH3) with the gold standard of H&E mitosis grade in surgical excision specimens (SES) using a cut-off of H&E mitosis grade in SES of 1 (A) and 3 (B).
See this image and copyright information in PMC

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