xRead - Nasal Obstruction (September 2024) Full Articles

20426984, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.23262, Wiley Online Library on [02/01/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

52

KUANetal.

TABLE V.7 (Continued)

Clinical endpoints 1. OS 2. Mutation profile 1. OS 2. Mutation profile

Study

Year LOE Study design Study groups

Conclusion

Bossi et al. 102

TP53 mutations were positive in 47% (surgery group) versus 39% (induction chemotherapy + surgery group) 1. 77% adenocarcinomas were TP53 mutation-positive 2. Wood exposure was associated with mutation positivity 1. 32.7% tumors ( n = 18)were EGFR positive 2. EGFR overexpression was higher in patients working in the wood industry TP53 mutations were present in 44% of ITAC cases

2012 4

Retrospective case series

Single center database ( n = 74)

Holmila et al. 101

2010 4

Retrospective case series

358 SNM were

collected from three European national registries between 1989 and 2002 (Denmark, Finland, and France)

Franchi et al. 105

2008 4

Retrospective case series

Single hospital case series of 55 ITACs

1. OS 2. DFS 3. Mutation profile

Perrone et al. 100

2003 4

Retrospective case series

H-ras mutations was investigated in 21 consecutive and untreated ITACs cases

Mutation profile

Abbreviations: ACC, adenoid cystic carcinoma; DFS, disease-free survival; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; ITAC, intestinal type adenocarcinoma; ONB, olfactory neuroblastoma; OS, overall survival; RFS, recurrence-free survival; SCC, squamous cell carcinoma.

alterations that account for the tumor’s most frequent mutations. 110 ONB can expresses somatostatin receptor (SSTR), specifically SSTR-2 (82%) and SSTR-5 (7.5%). Since both show the highest affinity with somatostatin ana logues, they can be used for diagnosis, especially in metastatic disease, using octreotide ( 111 In-pentetreotide) SPECT/CT and, more recently, Gallium-68 ( 68 Ga) PET/CT. Advantages are restricted time of image acquisition, better resolution, and lower radiation dose. 99,111 Classe et al. investigated ONB by looking at its molecular features and found two major subtypes: basal and neural subtypes. 112 Basal ONB had a high presence of a mutation in the IDH2 gene. This IDH2 mutation was also seen in other types of cancer, where it was found to lead to DNA hypermethylation and a failure of differentiation into the neuronal lineage. 113,114 These findings provide insights into the molecular basis of ONB and suggest that the IDH2 mutation could play a role in the development of ONB. The basal type is generally more aggressive and has a higher likelihood of distant disease. The neural type ONB is characterized by distinct patho logical, transcriptomic, proteomic, and immune features and shows genome-wide reprogramming with loss of DNA methylation at the enhancers of axonal guidance genes. 112 The prevalence of IDH2 mutations, which have signifi

cant implications for therapy with IDH inhibitors, is not as high in the neural ONB subtype compared to the basal subtype. 115 It is generally considered to be a more benign type of ONB, with a better prognosis and a lower likelihood of spreading. 112 One notable feature of sinonasal mucosal melanomas is their low tumor mutational burden, which refers to the number of genetic mutations present in the cancer cells. The well-known mutated genes involved in cuta neous melanoma tumorigenesis have only a marginal role in mucosal melanoma, reporting variable frequencies of mutations, as follows: 7%–30% in NRAS , 0%–25% in c KIT , 8%–11% in TERT , 3%–10% in BRAF (only in one study, 36%), 7% in SF3B1 , and KRAS mutations reported only in anecdotal cases. 99,116,117 This low mutational bur den has implications for treatment, as some of the newer immunotherapy treatments for cancer, such as checkpoint inhibitors, rely on the presence of certain genetic muta tions to be effective. 118 Given the low tumor mutational burden in mucosal melanomas, the role of checkpoint inhibitors in their treatment remains less defined. While some studies have shown promising results with the use of checkpoint inhibitors in this type of melanoma, further research is needed to fully understand the efficacy and optimal use of these treatments in this patient population.