Aggressive adreno-cortical carcinoma (ACC) associated with two rectal tumors (adenocarcinoma and neuro-endocrine) and somatic Kras mutation without microsatellite instability: is there a link?

Clara Leroy; Christine DoCao; Wassila Karrouz; Guillou Anne-Claire Le; Alexandra Derveaux; Marie-Pierre Buisine; R Perbet; Emmanuelle Leteurtre; Robert Caiazzo; Francois Pattou; Marie-Christine Vantyghem

doi:10.1530/endoabs.32.P557

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Endocrine Abstracts (2013) 32 P557 | DOI: 10.1530/endoabs.32.P557

ECE2013 Poster Presentations Endocrine tumours and neoplasia (66 abstracts)

Aggressive adreno-cortical carcinoma (ACC) associated with two rectal tumors (adenocarcinoma and neuro-endocrine) and somatic Kras mutation without microsatellite instability: is there a link?

Clara Leroy ¹ , Christine DoCao ¹ , Wassila Karrouz ¹ , Anne-Claire Le Guillou ¹ , Alexandra Derveaux ¹ , Marie-Pierre Buisine ² , R Perbet ³ , Emmanuelle Leteurtre ³ , Robert Caiazzo ^4, , Francois Pattou ^4, & Marie-Christine Vantyghem ^1,

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¹Endocrinology Department – CHRU, Lille, France; ²Oncogenetic Department – CHRU, Lille, France; ³Anatomopathology Department – CHRU, Lille, France; ⁴Endocrine Surgery Department – CHRU, Lille, France; ⁵U859 – INSERM – Lille 2 University, Lille, France.

Aggressive adreno-cortical carcinoma (ACC) is a rare, aggressive malignancy, with poorly understood molecular pathogenesis. As a result, therapeutic options are currently limited, surgery being currently the lone curative modality. Most cases of ACC are sporadic, although some familial cancer syndromes (Li–Fraumeni, Beckwith–Wiedemann, MEN1, Carney complex, congenital adrenal hyperplasia, etc.) are associated with an increased incidence of ACC. The genes involved in these syndromes, the adrenocorticotropic hormone-cAMP-protein-kinase-A and the β-catenin gene (CTNNB1), which lead to constitutive activation of Wnt signaling, are also implicated in ACC tumorigenesis. Understanding these pathways should lead to targeted therapy such as IGF, mTOR, steroidogenic factor-1, and MDR1 antagonists. Besides, rare cases of ACC are associated with colon cancer, sometimes associated with APC gene mutation and Lynch syndromes. We report a new case.

A partially deaf 43-year-old woman, with a narrow face, was diagnosed with ACC in reason of a painful 12 cm heterogeneous adrenal mass, secreting cortisol and androgens with angio-invasion impeding surgical resection. PET-FDG showed adrenal, lumbar and rectal uptake. Rectal biopsies showed a well-differentiated adenocarcinoma and a moderately-differentiated neuro-endocrine tumour. Rapidly occurring liver metastasis were in favour of poorly-differentiated ACC. The patient’s father had died from colonic perforation and her son had ulcerative colitis. Kras gene analysis on the colorectal carcinoma showed a somatic mutation (exon 2,V12G), but no microsatellite instability (phenotype MSS), rebutting Lynch syndrome. Kras and TP53 analysis in blood and liver metastasis are under investigation.

In conclusion, i) the association of two colorectal cancers with aggressive ACC is a particular challenge to define the priority of treatment between these two tumours; ii) the somatic Kras mutation inducing activation of the Ras/Raf/MEK/ERK pathway occurs in 40% of colorectal cancer but its role in ACC remains unknown. The involvement of Kras mutations in ACC could lead to new therapies such as Kras or PIK3 kinase inhibitors.