Atezolizumab in combination with nab-paclitaxel has been introduced for the treatment of locally advanced or recurrent triple negative breast cancer (TNBC). Patient selection relies on the use of immunohistochemistry using a specific monoclonal PD-L1 antibody (clone SP142) in a tightly controlled companion diagnostic test (CDx) with a defined interpretative algorithm. Currently there are no standardized recommendations for selecting the optimal tissue to be tested and there is limited data to support decision making, raising the possibility that tissue selection may bias test results. We compared PD-L1 SP142 assessment in a collection of 73 TNBC cases with matched core biopsies and excision samples. There was good correlation between PD-L1-positive core biopsy and subsequent excision, but we found considerable discrepancy between PD-L1 negative core biopsy and matched excision, with a third of cases found negative on core biopsies converting to positive upon examination of the excision tissue. In view of these findings, we developed a workflow for the clinical testing of TNBC for PD-L1 and implemented it in a central referral laboratory. We present audit data from the clinical PD-L1 testing relating to 2 years of activities, indicating that implementation of this workflow results in positivity rates in our population of TNBC similar to those of IMpassion130 clinical trial. We also developed an online atlas with a precise numerical annotation to aid pathologists in the interpretation of PD-L1 scoring in TNBC.
Colorectal cancer (CRC) has many subtypes with different prognoses and response to treatment. Patients must be characterized to access the most appropriate treatment and improve outcomes. An increasing number of biomarkers are required for characterization but are not in routine use. We investigated whether CRC can be stratified routinely within a small district general hospital to inform clinical decision making at local multidisciplinary team meeting/tumor board level. We evaluated mismatch repair (MMR) and EGFR signaling pathways using predominantly in-house immunohistochemical (IHC) tests (MSH2, MSH6, MLH1, PMS2, BRAF-V600E, Her2, PTEN, cMET) as well as send away PCR/NGS tests (NRAS, KRAS, and BRAF). We demonstrated that many of the tests required for personalized treatment of CRC can be done locally and timely. Send away tests need to be requested shortly after cut-up and this needs to be firmly established in the tissue pathways for the results to be considered at multidisciplinary team meeting/tumor board. We have shown that MMR IHC combined with BRAFV600E IHC is practical and easy to perform in a small district general hospital, has full concordance with DNA-based tests and satisfies the latest NICE requirements for the identification of potential Lynch syndrome patients. We provide a framework for the interpretation and presentation of test results. It is a practical classification that clinical pathologists can use to communicate effectively with the clinical team. It is broadly based on molecular subtyping, firmly focused on treatment decisions and dependent on the panel of molecular tests currently available.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
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