Loading
PTEN is the brake on the PI3K/AKT growth pathway; when a tumour deletes or mutates it (seen as a lost stain or on sequencing) the pathway runs unopposed. In hormone-treated breast cancer PTEN loss is one of the three changes that qualify a woman for capivasertib, in prostate cancer it marks aggressive disease, and in endometrial cancer it is almost universal in the NSMP group.
What is measured: loss of the PTEN phosphatase, by deletion, mutation or silencing. How: immunohistochemistry (loss in tumour cells with retained staining in stroma, validated in prostate cancer), next-generation sequencing of tissue or plasma for mutations and homozygous deletion, FISH for 10q23; germline PTEN testing for Cowden syndrome (macrocephaly, hamartomas, breast, thyroid and endometrial cancer risk). Frequencies: 50 to 80 percent of endometrial cancers (NSMP and mismatch repair-deficient classes), about 40 percent of glioblastomas, 20 percent of localised and 40 to 50 percent of castration-resistant prostate cancers (often with TP53 and RB1 loss), 5 to 7 percent of hormone receptor-positive breast cancers (PIK3CA, AKT1 and PTEN together about half), and melanoma and triple-negative breast cancer. What a result changes: in HR-positive, HER2-negative breast cancer after endocrine progression, a PIK3CA, AKT1 or PTEN alteration qualifies for capivasertib with fulvestrant (CAPItello-291, progression-free survival 7.3 against 3.1 months in the altered group); in prostate cancer PTEN loss carries an adverse prognosis, ipatasertib with abiraterone improved radiographic progression-free survival in PTEN-loss tumours in IPATential150 without approval, and capivasertib with abiraterone reported a benefit in CAPItello-281; in endometrial cancer it underpins mTOR and PI3K inhibitor trials and everolimus with letrozole; a germline finding sets lifelong surveillance. Where it matters: HR-positive breast cancer, metastatic prostate cancer, NSMP endometrial cancer and chromophobe RCC.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Shares Inavolisib, Alpelisib, AKT, Capivasertib.
Shares PTEN alteration (sequencing) and PTEN loss (IHC), Inavolisib, Alpelisib, Capivasertib.
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, AKT, Capivasertib.
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, AKT, Immunohistochemistry (IHC).
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, AKT, PIK3CA / PI3K-alpha.
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, AKT, Immunohistochemistry (IHC).
Shares AKT, Capivasertib, HR-positive metastatic breast cancer after CDK4/6 inhibitors, PIK3CA / PI3K-alpha.
Shares Inavolisib, Alpelisib, HR-positive metastatic breast cancer after CDK4/6 inhibitors, HR-positive / HER2-negative breast cancer.