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Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma).

ABSTRACT: Inverted papillomas are a unique group of locally aggressive benign epithelial neoplasms in the nasal cavity and paranasal sinuses arising from the Schneiderian mucosa. Metallothioneins are sulfhydryl-rich heavy metal-binding proteins required for metal toxicity protection and regulation of biological mechanisms including proliferation and invasion. The goal of this study was to identify three SNPs at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3'UTR region of the MT2A gene with IP risk and with tumor invasiveness according to Krouse staging. Genotyping was performed using the PCR restriction fragment length polymorphism technique in 130 genetically unrelated IP individuals, and 418 randomly selected healthy volunteers. The presence of the rs28366003 SNP was significantly related to the risk of IP within the present population-based case-control study. Compared to homozygous common allele carriers, heterozygosity and homozygosity for the G variant had a significantly increased risk of IP (adjusted odds ratio [OR]?=?7.71, 95% confidence interval [CI]: 4.01-14.91, p(dominant)?

SUBMITTER: Starska K

PROVIDER: S-EPMC4672009 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma).

Starska Katarzyna K Bryś Magdalena M Forma Ewa E Olszewski Jurek J Pietkiewicz Piotr P Lewy-Trenda Iwona I Stasikowska-Kanicka Olga O Danilewicz Marian M Krześlak Anna A

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20150603 11

Inverted papillomas are a unique group of locally aggressive benign epithelial neoplasms in the nasal cavity and paranasal sinuses arising from the Schneiderian mucosa. Metallothioneins are sulfhydryl-rich heavy metal-binding proteins required for metal toxicity protection and regulation of biological mechanisms including proliferation and invasion. The goal of this study was to identify three SNPs at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 ...[more]

PMID: 26036762

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Project description:There have been a few case reports and one small series of low grade papillary sinonasal (Schneiderian) carcinomas (LGPSC) which mimic papillomas but have overtly invasive growth and which occasionally metastasize. We describe the morphologic, clinical, immunohistochemical, and molecular features of five patients with LGPSC compared with eight cases each of inverted papilloma (IP) and conventional nonkeratinizing squamous cell carcinoma (SCC) with papillary growth. All LGPSC were nested with predominantly pushing invasion, no stromal reaction, and frequent surface papillary growth. All consisted of one cell type only, with polygonal cells with round nuclei, no (or limited) cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate. One patient had slightly more infiltrative bone invasion, another lymphovascular, perineural, and skeletal muscle invasion, and a third nodal metastasis after 17 years. By comparison, IPs had bland cytology, neutrophilic microabscesses, mixed immature squamous, goblet cell, and respiratory epithelium, and extremely low mitotic activity. Nonkeratinizing SCCs had basaloid-appearing cells with nuclear pleomorphism, brisk mitotic activity, and apoptosis. All LGPSC were p63 positive. Mitotic activity and Ki67 indices were significantly higher for LGPSCs than IPs and significantly lower than NKSCCs, while p53 immunohistochemistry in LGPSC was identical to nonkeratinizing SCC and higher than for IP. Sequencing showed all five tumors to harbor a MUC6 mutation, one tumor to harbor CDKN2A and PIK3R1 mutations, and one tumor to harbor a NOTCH1 mutation. All LGPSC lacked EGFR and KRAS mutations and lacked copy number variations of any main cancer genes. At a median follow up of 12 months, two LGPSC recurred locally, and one patient died after massive local recurrences and nodal metastases. LGPSC is a distinct, de novo sinonasal carcinoma that can be differentiated from papillomas by morphology and selected immunohistochemistry.

Dataset Information

Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma).

Publications

Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma).

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