Table 2. Expression of biomarkers in type 1 and type 2 endometrial cancer.

Target	Function	Change	Type 1, percentage	Type 2, percentage	Outcome	Potential targeted therapy
HER-2/ neu	Oncogene	Enhanced expression	Rare	18–80	Poor prognosis, aggressive tumor 57	HER2 inhibitors (afatinib 58 a, trastuzumab 37, and lapatinib 59 a)
ER and PR	Transcription factor	Enhanced expression	70–73	19–24	Improved overall survival 60	Tamoxifen, megestrol acetate 38, medroxyprogesterone acetate 61, letrozole 49, 51
p53	Tumor suppressor	Mutation	5–10	80–90	Poor prognosis 62	Anti-VEGF (bevacizumab) 63– 66
PIK3CA	Oncogene	Mutation	26–90 53	26–36	No association with survival, except exon 9 charge-changing mutations associated with worse survival 67	mTOR inhibitor 68, 69 (everolimus and temsirolimus 70) ± letrozole 49, 51
PTEN	Tumor suppressor	Mutation, deletion, methylation	35–55	0–11	Poor prognosis 71– 73	mTOR inhibitor 68, 69 (everolimus 74 and temsirolimus a), evaluating combination with olaparib ( ClinicalTrials.gov Identifier: NCT02208375)
EZH2	Transcription factor	Enhanced expression	16	36	Poor prognosis, aggressive tumor 75	EZH2 inhibitor a (EPZ-6438, ClinicalTrials.gov Identifier: NCT01897571)
K-ras	Oncogene	Mutation	13–26	0–10	Poor prognosis 76	MEK inhibitor 77, 78 a (trametinib, cobimetinib, and selumetinib b), GOG-2290 evaluating trametinib ± Akt inhibitor
MLH1	DNA repair	Methylation	20–35	0–10	No association with survival 79	Checkpoint inhibitor: Pembrolizumab 52, 80
PD-L1	Ligand for PD-1, immune checkpoint receptor on tumor-infiltrating lymphocytes	Expression on tumor cells	14–48 79, 81	33 82	Trend toward improved survival 83	Checkpoint inhibitor: Pembrolizumab 84
MSI	Downstream evidence of deficient DNA mismatch repair system	Polymerase chain reaction amplification of specific microsatellite repeats	33–40 79	2 53	No association with survival 79	Checkpoint inhibitor: Pembrolizumab 52, 80

First five columns adapted from Engelsen et al. ⁸⁵. ^aActionability shown in other cancer types ⁸⁶. ^bLow response rates (6%) shown in k-ras unselected population with selumetinib as single agent ⁸⁷. ER, estrogen receptor; EZH2, enhancer of zeste homolog 2; HER-2/neu, human epidermal growth factor receptor 2, protoconcogene Neu; K-ras, Kirsten RAt sarcoma virus; MLH1, MutL homolog 1; MSI, microsatellite instability; mTOR, mammalian target of rapamycin; PD-1, programmed death 1; PD-L1, programmed death ligand 1; PIK3CA, phosphatidylinositol 3-kinase catalytic subunit; PR, progesterone receptor; PTEN, phosphatase and tensin homolog; VEGF, vascular endothelial growth factor.