Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas.
Author(s): Lehr HA, Rochat C, Schaper C, Nobile A, Shanouda S, Vijgen S, Gauthier A, Obermann E, Leuba S, Schmidt M, C CR, Delaloye JF, Simiantonaki N, Schaefer SC
Publication: Mod Pathol, 2013, Vol. 26, Page 336-42
PubMed ID: 23041831 PubMed Review Paper? No
Purpose of Paper
This paper compared mitotic figure counts and percentage of MIB-1 immunostained tumor cells in matched biopsy and resection specimens from 52 breast carcinomas.
Conclusion of Paper
Mitotic figure counts were increased 3-fold in H-and-E stained resection specimens compared to biopsy specimens of tumors from 52 invasive ductal carcinoma patients. However, there was no correlation between biopsy size and mitotic figure counts and the percentage of post-metaphase mitotic figures was higher in biopsies, leading the authors to conclude differences in counts were due to continued cell cycle activity during formalin penetration of the surgical specimen. The discrepancy in mitotic figure counts resulted in only 60% concordance in SBR grading between biopsy and resection specimens from the same tumor. Immunostaining of tumor cells for MIB-1, a pan-cell-cycle-specific marker, was comparable between biopsy and resection specimens.
Studies
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Study Purpose
This study compared mitotic figure counts and percentage of MIB-1 immunostained tumor cells in matched biopsy and resected breast carcinoma specimens. Mitotic figure counts were performed by two observers on ten high power fields of 52 paired resection and biopsy specimens obtained from the same tumor. Quantification of MIB-1 was performed on each slide by visual estimation of 3-5 fields by 2 observers, hand counts of color print-outs from screen shots of virtual slides and analysis software of the screen shots from virtual slides. Biopsy slides were scanned and the size of biopsy cores was measured by image analysis.
Summary of Findings:
Mitotic figure counts were increased 3.4-fold in resection specimens (0 – 250 figures/field) compared to matched biopsies (0 – 64 figures/field) of the same tumors with a 3-fold increase when normalized by percentage of tumor cells vs stroma and non-neoplastic cells. Consequently, there was only 60% concordance in SBR grading based solely on mitotic figure counts between biopsy and resection specimens with 27% of cases (14 of 52) being of a higher grade and 10% of cases (5 of 52) a lower grade in the resection specimen than the biopsy specimen. Sub-classification of the mitotic figures showed a reduction in the percentage of post-metaphase (anaphase and telophase) figures from 7% in biopsies to 3% in resection specimens. The authors attribute these differences to the rate of formalin fixation which allows the continued cell cycle activity in resection specimens until resources dwindle, but arrests the process more quickly in biopsy specimens. There was no statistically significant difference in MIB-1 quantifications in any of the three methods between biopsies and resection specimens (20% vs 22% for visually estimated data, 22% vs 22% for counted data, and 14% vs 14% for image analysis, respectively); however, the ratio of MIB-1 over mitotic figures was significantly reduced in resection specimens (P<0.02). Image analysis revealed no statistical correlation between mitotic figure counts and biopsy size.
Biospecimens
Preservative Types
- Formalin
Diagnoses:
- Neoplastic - Carcinoma
Platform:
Analyte Technology Platform Cell count/volume H-and-E microscopy Protein Immunohistochemistry Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Method of tissue acquisition Mastectomy
Surgical resection
Biopsy
Biospecimen Aliquots and Components Aliquot size/volume Biopsies of 2.5 to 104 mm2
Immunohistochemistry Specific Data handling Estimated
Counted
Automated analysis