Characteristics of adrenocortical carcinoma associated with Lynch Syndrome.

CONTEXT Lynch syndrome (LS) is the most common inherited colorectal and endometrial cancer syndrome, caused by germline mutations in DNA mismatch repair (MMR) genes. It is also characterized by an increased risk of other tumours with lower prevalence, such as adrenal cortical carcinoma (ACC), an endocrine tumour with an incidence of < two cases/million individuals/year. Most ACC developed during childhood are associated with hereditary syndromes. In adults this association is not as well established as in children. Previous studies showed a 3.2% prevalence of LS among patients with ACC. EVIDENCE ADQUISITION The objective of this study is to determine the prevalence of ACC in a Spanish LS cohort and their molecular and histological characteristics. This retrospective study includes 634 patients from 220 LS families registered between 1999 and 2018. EVIDENCE SYNTHESIS During the follow-up three patients were diagnosed with ACC (0.47%), all were carriers of a MSH2 germline mutation. The three ACC patients presented loss of expression of MSH2 and MSH6 proteins. One tumour analysis showed loss of heterozygosity of the MSH2 wildtype allele. Our findings support previous data which considered ACC as a LS spectrum tumour. CONCLUSION MMR protein immunohistochemistry screening could be an efficient strategy to detect LS in patients with ACC.

[1]  E. Martinelli,et al.  Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  Aung Ko Win,et al.  Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database , 2019, Genetics in Medicine.

[3]  P. Møller,et al.  The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome , 2019, Genetics in Medicine.

[4]  Ravinder J. Singh,et al.  Adrenal Cortical Carcinoma Associated With Lynch Syndrome: A Case Report and Review of Literature , 2019, Journal of the Endocrine Society.

[5]  P. Keegan,et al.  FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors , 2019, Clinical Cancer Research.

[6]  Ahmet Zehir,et al.  Microsatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer. , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  Aung Ko Win,et al.  Cancer Risks for PMS2-Associated Lynch Syndrome. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  P. Salman,et al.  Evidence of response to pembrolizumab in a patient with Lynch syndrome-related metastatic colon cancer , 2018, OncoTargets and therapy.

[9]  T. Else,et al.  Adrenocortical carcinoma (ACC): When and why should we consider germline testing? , 2018, Presse medicale.

[10]  H. Cathro,et al.  Universal Lynch Syndrome Screening Should be Performed in All Upper Tract Urothelial Carcinomas , 2018, The American journal of surgical pathology.

[11]  J. Gilbert,et al.  Ectopic, retroperitoneal adrenocortical carcinoma in the setting of Lynch syndrome , 2018, Familial Cancer.

[12]  D. Evans,et al.  Association of Mismatch Repair Mutation With Age at Cancer Onset in Lynch Syndrome , 2017, JAMA oncology.

[13]  Ludmila V. Danilova,et al.  Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade , 2017, Science.

[14]  P. Møller,et al.  Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database , 2016, Gut.

[15]  Aung Ko Win,et al.  Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer , 2016, Cancer Epidemiology, Biomarkers & Prevention.

[16]  S. Nik-Zainal,et al.  Familial Adrenocortical Carcinoma in Association With Lynch Syndrome , 2016, The Journal of clinical endocrinology and metabolism.

[17]  C. Rodríguez-Galindo,et al.  5th International ACC Symposium: Hereditary Predisposition to Childhood ACC and the Associated Molecular Phenotype , 2016, Hormones and Cancer.

[18]  P. Møller,et al.  Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database , 2015, Gut.

[19]  Bert Vogelstein,et al.  PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. , 2015, The New England journal of medicine.

[20]  S. Ranganathan,et al.  Simultaneous Adrenocortical Carcinoma and Neuroblastoma in an Infant With a Novel Germline p53 Mutation. , 2015, Journal of pediatric hematology/oncology.

[21]  S. Gruber,et al.  Screening for germline mismatch repair mutations following diagnosis of sebaceous neoplasm. , 2014, JAMA dermatology.

[22]  R. Pai,et al.  Lynch Syndrome Screening Should Be Considered for All Patients With Newly Diagnosed Endometrial Cancer , 2014, The American journal of surgical pathology.

[23]  J. Church,et al.  Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer , 2014, The American Journal of Gastroenterology.

[24]  Rodney J Scott,et al.  Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database , 2013, Nature Genetics.

[25]  Larissa V Furtado,et al.  Adrenocortical carcinoma is a lynch syndrome-associated cancer. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  P. Møller,et al.  Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts , 2013, Gut.

[27]  S. Gruber,et al.  Prevalence of germline TP53 mutations in a prospective series of unselected patients with adrenocortical carcinoma. , 2013, The Journal of clinical endocrinology and metabolism.

[28]  J. Potter,et al.  Identification of Lynch syndrome among patients with colorectal cancer. , 2012, JAMA.

[29]  C. Sempoux,et al.  Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature. , 2012, Human pathology.

[30]  M. Fassnacht,et al.  TP53 germline mutations in adult patients with adrenocortical carcinoma. , 2012, The Journal of clinical endocrinology and metabolism.

[31]  A. Tabarin,et al.  Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'etude des Tumeurs Endocrines database. , 2012, European journal of endocrinology.

[32]  L. González,et al.  Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome , 2011, Familial Cancer.

[33]  Heather Hampel,et al.  Feasibility of screening for Lynch syndrome among patients with colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  Martin Fassnacht,et al.  Adrenocortical Carcinoma: Clinical Update , 2006 .

[35]  Electron Kebebew,et al.  Extent of Disease at Presentation and Outcome for Adrenocortical Carcinoma: Have We Made Progress? , 2006, World Journal of Surgery.

[36]  R. Broaddus,et al.  Unusual tumors associated with the hereditary nonpolyposis colorectal cancer syndrome , 2004, Modern Pathology.

[37]  A. Cats,et al.  Adrenocortical adenocarcinoma in an MSH2 carrier: coincidence or causal relation? , 2000, Human pathology.

[38]  P. Boyle,et al.  Cancer registration: principles and methods. Statistical methods for registries. , 1991, IARC scientific publications.