The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma

Helen Adderley; Samuel Rack; Brindley Hapuarachi; Laura Feeney; David Morgan; Tracy Hussell; Andrew J Wallace; Guy Betts; Clare Hodgson; Kevin Harrington; Robert Metcalf

doi:10.1016/j.oraloncology.2020.105095

The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma

Helen Adderley, Samuel Rack, Brindley Hapuarachi, Laura Feeney, David Morgan, Tracy Hussell, Andrew J Wallace, Guy Betts, Clare Hodgson, Kevin Harrington, Robert Metcalf^*

^*Corresponding author for this work

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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.

Original language	English
Article number	105095
Journal	Oral Oncology
Volume	113
Early online date	05 Dec 2020
DOIs	https://doi.org/10.1016/j.oraloncology.2020.105095
Publication status	Published - Feb 2021

Bibliographical note

Keywords

Biomarkers, Tumor/metabolism
Carcinoma, Adenoid Cystic/genetics
Class I Phosphatidylinositol 3-Kinases/metabolism
Female
Humans
Male
Salivary Gland Neoplasms/genetics
Tumor Suppressor Protein p53/metabolism

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The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma
Copyright 2020 the authors. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 1.55 MBLicence: CC BY-NC-ND

Cite this

@article{fbe5df421fd9487f97656a56c61aa31d,

title = "The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma",

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.",

keywords = "Biomarkers, Tumor/metabolism, Carcinoma, Adenoid Cystic/genetics, Class I Phosphatidylinositol 3-Kinases/metabolism, Female, Humans, Male, Salivary Gland Neoplasms/genetics, Tumor Suppressor Protein p53/metabolism",

author = "Helen Adderley and Samuel Rack and Brindley Hapuarachi and Laura Feeney and David Morgan and Tracy Hussell and Wallace, {Andrew J} and Guy Betts and Clare Hodgson and Kevin Harrington and Robert Metcalf",

year = "2021",

month = feb,

doi = "10.1016/j.oraloncology.2020.105095",

language = "English",

volume = "113",

journal = "Oral Oncology",

issn = "1368-8375",

publisher = "Elsevier Ltd",

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TY - JOUR

T1 - The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma

AU - Adderley, Helen

AU - Rack, Samuel

AU - Hapuarachi, Brindley

AU - Feeney, Laura

AU - Morgan, David

AU - Hussell, Tracy

AU - Wallace, Andrew J

AU - Betts, Guy

AU - Hodgson, Clare

AU - Harrington, Kevin

AU - Metcalf, Robert

PY - 2021/2

Y1 - 2021/2

N2 - 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.

AB - 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.

KW - Biomarkers, Tumor/metabolism

KW - Carcinoma, Adenoid Cystic/genetics

KW - Class I Phosphatidylinositol 3-Kinases/metabolism

KW - Female

KW - Humans

KW - Male

KW - Salivary Gland Neoplasms/genetics

KW - Tumor Suppressor Protein p53/metabolism

U2 - 10.1016/j.oraloncology.2020.105095

DO - 10.1016/j.oraloncology.2020.105095

M3 - Article

C2 - 33290961

SN - 1368-8375

VL - 113

JO - Oral Oncology

JF - Oral Oncology

M1 - 105095

ER -

The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma

Abstract

Bibliographical note

Keywords

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