Phenotype–genotype correlation: Challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses

Frattini, Milo; Perrone, Francesco; Suardi, Simona; Balestra, Debora; Caramuta, Stefano; Colombo, Federica; Licitra, Lisa; Cantù, Giulio; Pilotti, Silvana

doi:10.1002/hed.20433

Cited by 37 publications

(40 citation statements)

References 22 publications

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“…Our data are consistent with previous studies demonstrating that ITACs share genetic similarities with microsatellite stable colorectal cancers [32,33]. Until now, the involvement of APC in ITACs has been poorly examined.…”

Section: Discussionsupporting

confidence: 93%

“…Until now, the involvement of APC in ITACs has been poorly examined. To our knowledge, a single mutational study of the gene has been performed, reporting only missense mutations, which might not affect the APC protein activity [32]. In this study, we demonstrated a concurrent hypermethylation and allelic loss of APC that determined lack of protein expression in the neuroendocrine component.…”

Section: Discussionmentioning

confidence: 63%

“…This result was not unexpected because, in several studies, a lower frequency of KRAS mutations has been reported in ITACs compared with colorectal carcinomas [17]. There is less information about BRAF mutation, which was not found in any of the 18 cases investigated in a recent published series [32].…”

Section: Discussionmentioning

confidence: 65%

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Mixed Exocrine-Neuroendocrine Carcinoma of the Nasal Cavity: Clinico-Pathologic and Molecular Study of a Case and Review of the Literature

Rosa¹,

Furlan

Franzi

et al. 2012

Head and Neck Pathol

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Sinonasal intestinal-type adenocarcinomas (ITACs) are rare neoplasms histologically resembling intestinal adenocarcinomas. Although a neuroendocrine differentiation in ITACs has been described, true mixed exocrine-neuroendocrine carcinomas, neoplasms in which each component represents at least 30 % of the lesion, are extremely rare and their molecular alterations are largely unknown. We describe herein the clinico-pathologic features, the methylation profile, chromosomal gains and losses, and mutation analysis of KRAS, BRAF and p53 in a nasal mixed exocrine-neuroendocrine carcinoma resected in a 79-year-old man. The tumor was composed of an ITAC and a poorly differentiated neuroendocrine carcinoma. Both exocrine and neuroendocrine components were CK8, CK20, CDX2 and p53 positive, and CK7 and TTF1 negative. The neuroendocrine component also showed immunoreactivity for chromogranin A, synaptophysin, serotonin and glicentin. Gains and losses were found at following chromosome regions: 17p13 (TP53), 14q24 (MLH3), 19q13 (KLK3), 5q21 (APC), 7q21 (CDK6), 9q34 (DAPK1), 12p13 (TNFRSF 1A, CDKN1B), 13q12 (BRCA2), 17p13.3 (HIC1), 18q21 (BCL2), and 22q12 (TIMP3). Aberrant methylation was detected only in the neuroendocrine component and involved APC and DAPK1 genes. No mutation of KRAS (exons 2-4), BRAF (exon 15), and p53 (exons 4-10) was found in both components. The results suggest a monoclonal origin of the tumor from a pluripotent cell undergoing a biphenotypic differentiation and that the neuroendocrine differentiation may be from an exocrine to an endocrine pathway. We have also reviewed the literature on sinonasal mixed exocrine-neuroendocrine carcinomas to give to the reader a comprehensive overview of these very rare tumor types.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 63%

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Mixed Exocrine-Neuroendocrine Carcinoma of the Nasal Cavity: Clinico-Pathologic and Molecular Study of a Case and Review of the Literature

Rosa¹,

Furlan

Franzi

et al. 2012

Head and Neck Pathol

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“…11 Further attempts to find genetic alterations as described in colorectal adenocarcinoma concerned APC, b-catenin, and various mismatch repair genes gave negative results. 10,15,17 These results indicate that ITAC and colorectal adenocarcinoma have different genetic pathways of development and progression.…”

mentioning

confidence: 90%

Genome‐wide analysis of genetic changes in intestinal‐type sinonasal adenocarcinoma

et al. 2009

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“…2,3,5 Little is known about genetic alterations in human sinonasal cancer, published findings being based on a relatively limited number of cases and mostly involving adenocarcinoma tumors; the adenocarcinomas have often been those from an ethmoidal location or classified as of intestinal type. In these studies, high frequencies of DNA copy number changes as detected by comparative genomic hybridization have been detected, 17,18 whereas mutation rates reported for the KRAS gene [19][20][21][22][23][24] and the TP53 tumor suppressor gene have been lower. 23,[25][26][27] This study sought to clarify whether mutational mechanisms are involved in sinonasal carcinogenesis and their relation to wood-dust exposure.…”

mentioning

confidence: 99%

Mutations in TP53 tumor suppressor gene in wood dust‐related sinonasal cancer

Holmila

Bornholdt

Heikkilä

et al. 2010

Intl Journal of Cancer

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The causal role of work-related exposure to wood dust in the development of sinonasal cancer has long been established by numerous epidemiologic studies. To study molecular changes in these tumors, we analyzed TP53 gene mutations in 358 sinonasal cancer cases with or without occupational exposure to wood dust, using capillary electrophoresis single-strand conformation polymorphism analysis and direct sequencing. A significant association between wood-dust exposure and adenocarcinoma histology was observed [adjusted odds ratio (OR) 12.6, 95% confidence interval (CI), 5.0-31.6]. TP53 mutations occurred in all histologies, with an overall frequency of 77%. TP53 mutation positive status was most common in adenocarcinoma (OR 2.0, 95% CI, 1.1-3.7; compared with squamous cell carcinoma), and mutation positivity showed an overall, nonsignificant association with wood-dust exposure (OR 1.6, 95% CI, 0.8-3.1). Risk of TP53 mutation was significantly increased in association with duration (!24 years, OR 5.1, 95% CI, 1.5-17.1), average level (>2 mg/m 3 ; OR 3.6, 95% CI, 1.2-10.8) and cumulative level (!30 mg/m 3 3 years; OR 3.5, 95% CI, 1.2-10.7) of wood-dust exposure; adjustment for formaldehyde affected the ORs only slightly. Smoking did not influence the occurrence of TP53 mutation; however, it was associated with multiple mutations (p 5 0.03). As far as we are aware, this is the first study to demonstrate a high prevalence of TP53 mutation-positive cases in a large collection of sinonasal cancers with data on occupational exposure. Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer.

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Phenotype–genotype correlation: Challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses

Cited by 37 publications

References 22 publications

Mixed Exocrine-Neuroendocrine Carcinoma of the Nasal Cavity: Clinico-Pathologic and Molecular Study of a Case and Review of the Literature

Mixed Exocrine-Neuroendocrine Carcinoma of the Nasal Cavity: Clinico-Pathologic and Molecular Study of a Case and Review of the Literature

Genome‐wide analysis of genetic changes in intestinal‐type sinonasal adenocarcinoma

Mutations in TP53 tumor suppressor gene in wood dust‐related sinonasal cancer

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