Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma)
TL;DR: The findings suggest that MT2A gene variation rs28366003 may be implicated in the etiology of sinonasal inverted papilloma in a Polish population.
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 < 0.001). Moreover, risk allele carriers demonstrated higher Krouse stage (pT1 vs. pT2-4) (OR = 19.32; 95 % CI, 2.30–173.53; p < 0.0001), diffuse tumor growth (OR = 4.58; 95 % CI, 1.70–12.11; p = 0.0008), bone destruction (OR = 4.13; 95 % CI, 1.50–11.60; p = 0.003), and higher incidence of tumor recurrences (OR = 5.11; 95 % CI, 1.68–15.20; p = 0.001). The findings suggest that MT2A gene variation rs28366003 may be implicated in the etiology of sinonasal inverted papilloma in a Polish population.
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TL;DR: A deeper understanding of the functional, biochemical and molecular characteristics of MT2A would be identified, in order to bring new opportunities for oxidative stress therapy.
Abstract: Mammalian metallothionein-2A (MT2A) has received considerable attention in recent years due to its crucial pathophysiological role in anti-oxidant, anti-apoptosis, detoxification and anti-inflammation. For many years, most studies evaluating the effects of MT2A have focused on reactive oxygen species (ROS), as second messengers that lead to oxidative stress injury of cells and tissues. Recent studies have highlighted that oxidative stress could activate mitogen-activated protein kinases (MAPKs), and MT2A, as a mediator of MAPKs, to regulate the pathogenesis of various diseases. However, the molecule mechanism of MT2A remains elusive. A deeper understanding of the functional, biochemical and molecular characteristics of MT2A would be identified, in order to bring new opportunities for oxidative stress therapy.
70 citations
TL;DR: A systematic review with meta-analysis confirmed that the potential malignancy of Schneiderian papilloma should not be underestimated and showed the paucity of studies investigating the molecular alterations which may be related with the malignant transformation of SNIP.
Abstract: Schneiderian papillomas are uncommon tumors which may develop within the nasal cavity and comprise three well-defined histological types: sinonasal inverted papilloma (SNIP), exophytic papilloma, and oncocytic papilloma. It is well known the rate of Schneiderian papilloma may also present a malignant degeneration and SNIP represents the most important subgroup in consideration of its frequency and malignant propensity. Although HPV infection is always considered the first event favoring the development of SNIP, however, it is not established as an eventual connection between viral actions and malignant transformation. In fact, different molecular mechanisms are suspected to play a crucial role in this process and, currently, many authors agree that only by improving our knowledge about these mechanisms it will be possible to achieve new and effective targeted therapies. So the aim of this study was firstly to systematically review the literature focusing on different biomarkers that could be implicated in the stages of SNIP malignant degeneration. Secondly, a systematic review with meta-analysis was performed to better define the incidence of sinonasal malignancies originating from Schneiderian papilloma (SNIP, exophytic papilloma, and oncocytic papilloma). Twenty-nine studies comprising a total of 3177 patients were statistically analyzed. Results showed a 9% (95% CI = 7–11) overall rate of malignant transformation from Schneiderian papilloma. In conclusion, this analysis confirmed that the potential malignancy of Schneiderian papilloma should not be underestimated. On the other hand, our review showed the paucity of studies investigating the molecular alterations which may be related with the malignant transformation of SNIP.
49 citations
TL;DR: An important issue is still the need for a biomarker indicative of inverted papilloma and its malignant transformation, and the procedures are still lacking in explicit and standardized postoperative management guidelines.
Abstract: Sinonasal inverted papilloma is a relatively rare disease; however, it is prevalent enough for every ENT practitioner to encounter it several times throughout medical routines. Despite the developments in experimental and clinical medicine as well as surgical techniques, our knowledge of this disease is still inadequate. With improved imaging and better diagnostic techniques, proper diagnosis and qualification for surgical approaches leave no doubt. Although the endoscopic approach seems to be the gold standard for such condition, some cases may additionally require an external approach. Regardless of the type of surgery, postoperative management is crucial for both healing and long-term follow-up. Unfortunately, the procedures are still lacking in explicit and standardized postoperative management guidelines. Moreover, an important issue is still the need for a biomarker indicative of inverted papilloma and its malignant transformation. Several particles, within the spotlight of the researchers, have been SCCA, Ki-67, Bcl-2, Wnt proteins, and many more. Nevertheless, the topic requires further investigations.
27 citations
22 Feb 2017
TL;DR: The results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.
Abstract: Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.
25 citations
Cites background from "Metallothionein 2A core promoter re..."
...Rs28366003 locates in the core promoter region, while rs10636 polymorphism is in the 3’UTR region of the MT2A gene [17]....
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...And, the researchers found that MT1/MT2 may play an important role in tumors via several crucial mechanisms including modulating p53 zinc-dependent activity, inhibiting NF-κB signaling, and regulating the PIK3/AKT and Rb/E2F pathways [15-17]....
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TL;DR: A growing body of evidence suggests that molecular alteration in SIP, including human papilloma virus infections, single nucleotide polymorphisms of key genes, deregulation of signaling pathways and immunological changes, may lead to SIP occurrence and malignant transformation.
Abstract: Sinonasal inverted papilloma (SIP) is a benign tumor of the nasal cavity and sinus. SIP is characterized by aggressive malignant transformation and a high rate of recurrence. Inadequate removal of the tumor during surgery is one of the most significant contributors to SIP recurrence. A growing body of evidence suggests that molecular alteration in SIP, including human papilloma virus infections, single nucleotide polymorphisms of key genes, deregulation of signaling pathways and immunological changes, may lead to SIP occurrence and malignant transformation. However, the extent to which these molecular mechanisms contribute to SIP pathology and transformation remains unclear due to limited research. Further studies are warranted to elucidate the primary dependent factors that contribute to SIP etiology. The present article reviewed risk factors of progression and recurrence of SIP, including outdoor and industrial occupational exposure, smoking, septal deviation, SIP location, recurrent cases, stage of SIP-associated squamous cell carcinoma and choice of surgical method.
20 citations
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...central nervous system, and thyroid cancers [10, 25, 44]....
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TL;DR: World Health Organization Collaborating Center for International Histological Classification of Tu-mors, Armed Forces Institute of Pathology, Wash-ington, DC.
Abstract: World Health Organization Collaborating Centerfor International Histological Classification of Tu-mors, Armed Forces Institute of Pathology, Wash-ington, DC.Address for reprints: Leslie H. Sobin, M.D., ArmedForces Institute of Pathology, Alaska Avenue and14th Street, Building 54, Room 3009, Washington,DC 20306-6000.Received March 23, 2000; accepted March 23,2000.
2,578 citations
Book•
01 Sep 2005
TL;DR: 1. Nasal cavity and paranasal sinuses, Hypopharynx, larynx and trachea, and paraganglionic systems.
Abstract: 1. Nasal cavity and paranasal sinuses 2. Nasopharynx 3. Hypopharynx, larynx and trachea 4. Oral cavity and oropharynx 5. Salivary glands 6. Odontogenetic tumours 7. Ear 8. Paraganglionic systems
1,974 citations
TL;DR: This study develops a uniformly applied staging system representing the extent of disease in inverted papillomas of the nose and sinuses that could be easily applied in outcomes research.
Abstract: Objectives Inverted papillomas of the nose and sinuses are uncommon neoplasms. In the past decade there has been a trend toward the use of endoscopic surgical techniques in the management of these tumors, in contrast to the extensive open procedures recommended previously. This trend has not been without controversy, given the association of inverted papillomas with malignancy. It has been difficult to compare surgical approaches to these neoplasms, because of the absence of a uniformly applied staging system representing the extent of disease. It was the purpose of this study to develop such a system that could be easily applied in outcomes research.
Study Design This study involved an integrated literature review and a synthesis of findings from a number of studies.
Methods Previous and current clinical studies examining the treatment of inverted papilloma were reviewed. Findings were organized, and a staging system was framed based on this review.
Results A simple, easily applied staging system was developed based on the extent of tumor involvement noted on endoscopic examination of the nasal cavity and computed tomography (CT) scan evaluation.
Conclusions Stage I disease is limited to the nasal cavity alone. Stage II disease is limited to the ethmoid sinuses and medial and superior portions of the maxillary sinuses. Stage III disease involves the lateral or inferior aspects of the maxillary sinuses or extension into the frontal or sphenoid sinuses. Stage IV disease involves tumor spread outside the confines of the nose and sinuses, as well as any malignancy.
341 citations