Juvenile nasopharyngeal angiofibroma in familial adenomatous polyposis: a new extracolonic manifestation.

R Valanzano MD^a, MC Curia PhD^b, M Fedi MD^a, G Aceto PhD^b, S Veschi PhD^b, L De Lellis PhD^a, F Tonelli MD^a

^aUniversity of Florence, Florence, Italy, ^bDipartimento di Oncologia e Neuroscienze – Sezione di Patologia Molecolare- Università “Gabriele D’Annunzio”, Chieti, Italy

Aim: Juvenile Nasopharingeal Angiofibroma (JNA) is a rare vascular neoplasm that affects predominantly male adolescents. An association between JNA and Familial Adenomatous Polyposis (FAP) has been reported and mutations or allelic loss of the adenomatous polyposis coli (APC) gene have therefore considered implied in the pathogenesis of JNA [Giardiello FM et al. Gastroenterology 1993;105:1550-2. Ferouz AS et al. Otolaryngol Head Neck Surg 1995;113(4):435-9]. However, no somatic mutations of APC gene have been jet detected in JNA tissue [Abraham SC, et al. Am J Pathol 2001;158:1073-8. Guertl B et al. Hum Pathol 2000;31:1411-3]. Methods: We observed a JNA in a 24-years-old man with FAP and germ-line APC mutation at codon 1309 (exon 15). The patient was already submitted to restorative proctocolectomy and resection of abdominal wall desmoid tumor. For the JNA he underwent a radical transphenoidal tumor resection. In vitro synthesized protein (IVSP) technique followed by heteroduplex analysis on agarose minigel (HAAM) to discriminate alleles, was performed on JNA and desmoid samples. Results:. We detected a 5bp deletion at codon 1061 at the APC gene in DNA sample from JNA tissue. The truncating mutation, was detected both in JNA and desmoid tumor. Conclusions: this findings are the first demonstration of a genetic association between FAP and JNA and between a germline mutation at codon 1309 and somatic mutation at codon 1061. Moreover, the somatic mutation was found in the zone 1020-1169 that affects the β-catenin binding domain. High frequency of ß-catenin somatic mutations in stromal cells of sporadic JNAs have been recently described (Abraham SC, et al. Am J Pathol 2001;158:1073-8). These observations suggest that JNAs may arise through alterations of the APC/ß-catenin pathway.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 892 (Genetic predisposition - Part II).