Pten ihc as a predictor of mismatch repair status in breast cancerI T 1 0 2 0 1 8 0 0 0 0 1 0 7 3 0
PTEN analysis by immunohistochemistry (IHC) identifies 95%-100% of mismatch repair (MMR)-proficient (pMMR) breast cancers. These patients do not require further investigations for MMR and microsatellite instability (MSI).
The majority of breast cancers (⁓71%) are pMMR; the expression of the MMR proteins shows high levels of intra-tumor heterogeneity (⁓13%), these tumors being clinically pMMR; therefore, loss of the MMR proteins does not necessarily mean that the tumor is dMMR. The Food and Drug Administration (FDA) allows pembrolizumab (an immunotherapeutic agent blocking the PD1/PD-L1 axis) in al MMR-deficient (dMMR) tumors, regardless of their histology. To date no breast-specific tests are available for MMR status assessment, which is currently investigated through vastly heterogeneous locally-developed tests, such as IHC for the four MMR proteins (MLH1, MSH2, MSH6, and PMS2), or surrogate tests, such as MSI analyses. MMR IHC is not mirrored by MSI in breast cancers, the latter
analysis being insufficient in these patients. The expression of PTEN is homogeneous in breast cancer and is highly related to the MMR status.
Policlinico Hospital & Statale University researchers developed a laboratory protocol and diagnostic algorithm for the selection of breast cancer patients eligible for immunotherapy. This technology is breast-specific and uses a single monoclonal antibody clone against PTEN with definite dilution and antigen retrieval methods as first-line analysis. A scoring system has been specifically developed for breast cancer: if PTEN expression is retained, subsequent studies can be avoided in breast cancer patients’ selection for immunotherapy.
Patent pending in Italy.
- N. Fusco
- S. Bosari
- S. Ferrero Bogetto
- G. Lopez
- C. Corti