The Journal of Bone and Joint Surgery, Vol 67, Issue 3 404-413, Copyright © 1985 by Journal of Bone and Joint Surgery, Inc
Grading of bone tumors by analysis of nuclear DNA content using flow cytometry
HJ Mankin, JF Connor, AL Schiller, N Perlmutter, A Alho and M McGuire
We studied 217 consecutive tumors of bone by flow cytometric analysis of
nuclear DNA concentration after staining with propidium iodide. A diagnosis
and histological grade (benign, low-grade, or high-grade sarcoma) were
assigned to each tumor on the basis of staging data (with the exception of
the forty-six giant-cell tumors, which, although indistinguishable
histologically, were divided according to the flow cytometric pattern into
two distinct groups), and we quantitatively studied the flow cytometry data
to assess the percentages of cells in diploidy, tetraploidy, or aneuploidy.
When compared, the mean values for the flow cytometric data for the three
grades showed significant differences. Criteria were established for the
three classes of tumors: for benign tumors, less than 11 per cent
tetraploidy and no aneuploidy; for low-grade sarcomas, more than 11 per
cent and less than 17 per cent tetraploidy, and no aneuploidy; and for
high-grade tumors, either more than 17 per cent tetraploidy or aneuploidy.
Tests for compliance for all groups of tumors (excluding the forty-six
giant-cell tumors)--benign, low grade, or high grade--were significant for
most of the benign lesions (with the exception of chondroblastoma and
fibrous dysplasia) and for the high-grade sarcomas (with the exception of
round-cell tumors). The low-grade sarcomas did far less well, based
principally on the failure of the low-grade chondrosarcomas, chordomas, and
adamantinomas to comply with the criteria. An attempt to assess the value
of the system as a predictor of metastases showed that a low percentage of
diploid cells (less than 75 per cent) and the presence of an aneuploid peak
correlated statistically with the development of metastatic disease, but
the usefulness of this observation could not be fully assessed because of
multiple variables, associated principally with treatment.
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