Helen Adderley1, Samuel Rack2, Brindley Hapuarachi1, Laura Feeney3, David Morgan4, Tracy Hussell4, Andrew J Wallace5, Guy Betts2, Clare Hodgson1, Kevin Harrington6, Robert Metcalf7. 1. The Christie NHS Foundation Trust, Manchester, United Kingdom. 2. Manchester University NHS Foundation Trust, Manchester, United Kingdom. 3. Queen's University Belfast, Belfast, United Kingdom. 4. The University of Manchester, Manchester, United Kingdom. 5. NW GLH, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 6. The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust National Institute of Health Research Biomedical Research Centre, London, United Kingdom. 7. The Christie NHS Foundation Trust, Manchester, United Kingdom. Electronic address: robert.metcalf1@nhs.net.
Abstract
OBJECTIVES: Despite wide excision and post-operative irradiation, loco-regional and/or metastatic recurrence is a significant clinical problem in salivary adenoid cystic carcinoma (SACC). Reliable biomarkers are required to tailor post-treatment surveillance to patients at highest risk of recurrence. We sought to determine the utility of TP53 and PIK3CA mutations as prognostic biomarkers in SACC. MATERIALS AND METHODS: DNA was extracted from archival tumour blocks of 145 SACC patients from 66 UK referral centres and sequenced for TP53 and PIK3CA mutations. Clinical, pathological and outcome data were analysed to determine the impact of the genomic alterations on disease recurrence and overall survival (OS). RESULTS: TP53 and PIK3CA mutations were identified in 8% (10/121 successful analyses) and 2% (3/121) of cases, respectively. There were too few PIK3CA mutations in this cohort for informative further analysis. TP53-mutated SACC had significantly shorter median OS (5.3 vs. 16.3 years, p = 0.019) and lower 10-year survival (48% vs. 81%) compared with TP53 wild-type ACC. Solid-pattern histopathology was more frequent in TP53-mutated SACC (50% vs. 15%, p = 0.27). CONCLUSION: TP53-mutated recurrent and metastatic SACC was associated with shorter OS, which was significant when combined with published genomic data sets. Stratifying by TP53 status, in addition to established clinical, pathological and genomic biomarkers, may usefully inform follow-up strategy.
OBJECTIVES: Despite wide excision and post-operative irradiation, loco-regional and/or metastatic recurrence is a significant clinical problem in salivary adenoid cystic carcinoma (SACC). Reliable biomarkers are required to tailor post-treatment surveillance to patients at highest risk of recurrence. We sought to determine the utility of TP53 and PIK3CA mutations as prognostic biomarkers in SACC. MATERIALS AND METHODS: DNA was extracted from archival tumour blocks of 145 SACC patients from 66 UK referral centres and sequenced for TP53 and PIK3CA mutations. Clinical, pathological and outcome data were analysed to determine the impact of the genomic alterations on disease recurrence and overall survival (OS). RESULTS:TP53 and PIK3CA mutations were identified in 8% (10/121 successful analyses) and 2% (3/121) of cases, respectively. There were too few PIK3CA mutations in this cohort for informative further analysis. TP53-mutated SACC had significantly shorter median OS (5.3 vs. 16.3 years, p = 0.019) and lower 10-year survival (48% vs. 81%) compared with TP53 wild-type ACC. Solid-pattern histopathology was more frequent in TP53-mutated SACC (50% vs. 15%, p = 0.27). CONCLUSION:TP53-mutated recurrent and metastatic SACC was associated with shorter OS, which was significant when combined with published genomic data sets. Stratifying by TP53 status, in addition to established clinical, pathological and genomic biomarkers, may usefully inform follow-up strategy.
Authors: Samuel Rack; Laura Feeney; Brindley Hapuarachi; Helen Adderley; Laura Woodhouse; Guy Betts; George J Burghel; Kevin J Harrington; Robert Metcalf Journal: Cancers (Basel) Date: 2022-02-23 Impact factor: 6.639