Original Stage I's with high KI-67 that progressed?

[Hopeful]

Here is an excerpt from an article on Measuring Proliferation in Breast Cancer:

The Ki67 labelling index is now widely used as the measure of proliferation. Ki67 is a protein expressed in the nucleus during the cell cycle [22]. Cells express the antigen during G1, S, G2 and M phases, but not during G0. The original antibodies raised against Ki67 required fresh or frozen tumour specimens. Cells that showed specific nuclear staining were scored as positive and the Ki67 labelling index was expressed as the percentage of the total number of tumour cells that stain positive; this equates to the growth fraction of the tumour. Higher grade cancers have higher Ki67 indices – one study found mean scores of 9% in grade I tumours, 14% in grade II and 26% in grade III [23]. The Ki67 index correlates significantly with estimates of the mitotic index [24] and SPF by flow cytometry [13,25,26], although some of the published correlation coefficients are modest (r = 0.42 [13], r = 0.22 [26]). Various studies have shown correlations between Ki67 and disease-free and overall survival, with an increased risk of recurrence in tumours with a high Ki67 [27-33]. Pierga and colleagues [34] performed a multivariate analysis and showed the Ki67-determined growth fraction to be an independent prognostic factor (p = 0.03) along with nodal status, age and adjuvant treatment received.

Hope this is useful.

Hopeful

[CLTann]

Thank you very much Hopeful for explaining and citing reference on the Ki67 index. One more question: if Ki67 correlates well with the grading system, would the grading score be just as good a measure for the proliferation status?


Thanks.

[Hopeful]

CLTann,

The grading system is actually an average of three different dimensions of the tumor: cell divison or proliferation, cell structure, and nuclear grade. Each of these elements gets a score from 1 to 3. Theoretically, you could have a tumor that was scored highly on the two non-proliferation elements, yet was very slowly dividing. In that case, the Ki-67 probably would not correlate well with the grade. The text from the article I posted reflects that, as a general rule, the higher the grade, the more proliferative the tumor, which seems logical. Whether grade alone can be seen as a surrogate for proliferation is probably pushing the envelope a bit. For example, my own pathology has an aggressive element (Her2 3+ by IHC) but relatively low proliferation (Ki-67 11%), and the pathogist assigned a grade II based on the three elements. The feature that was scored the highest on my report was neither the proliferation nor the nuclear grade, but the cell structure - apparently my tumor cells were highly undifferentiated, meaning that if they were able to take up residence in a "new neigborhood," so to speak, they would have little problem blending in. What I take from the entire Ki-67 discussion is that there is no single element that we can point to that will lead to a definitive answer - there are just a million pieces to a jigsaw puzzle, and no one knows how they all come together yet.

Hopeful