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. 2022 Apr 8;12:805613. doi: 10.3389/fonc.2022.805613

Table 1.

POLE: recommendations and comments from the working group.

Recommendations
A) No surrogate for POLE mutation still exists but the targeted sequencing for the common mutations in this gene could be used rather than whole genome or panel testing (mutation analysis of the exonuclease domain of POLE exons 9, 11, 13, and 14).
Comments
The mutational analysis of the exonuclease domain of POLE should be considered in the following cases:

  • - EEC G3 and other high-grade histologies (UEC/DEC, clear cell, carcinosarcoma)

  • - rare histotypes (neuroendocrine tumors)

  • - abundance in TIL and/or peritumoral lymphocytes

  • - mixed cases

  • - ambiguous morphologies

  • - ambiguous immunophenotype (possible multiple classifiers)

  • - subclonal p53 at IHC

Mutational analysis should be carried out only in selected experienced centers.
Minimal requirement is the adequate assessment of the 5 more frequent occurring POLE hotspot variants. Unknown variants or VUS should be discussed at the Tumor Board.