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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Is the frequency of mitoses and PCNA positive cells in tissues affected by delay in fixation? Lessons for accurate tumor grading.

Using uniform systematic random sampling, we tested whether a drop in mitoses and PCNA (proliferation cell nuclear antigen) positive cells following a delay in tissue fixation of up to five hours, would be unequivocally discernible at the well perfused periphery from 11 aggressive rat adenocarcinomas. No statistically significant difference (0.05 < P < 0.10; 95% Cl (-13.3, 1.3)) was found. We attributed this finding to the high proliferative heterogeneity of rapidly growing solid tumors because: (1) vascular perfusion is heterogeneous as rapidly proliferating epithelial tumors tend to outgrow their blood supply; (2) the ratio of perfused/ non-perfused tumor volumes may change as a solid tumor grows, altering to the same extent the ratio of proliferative vs. non proliferative regions in the tumor; and (3) the duration of mitoses is not constant. The consequences for accurate tumor grading are discussed.[1]

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