TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma

Campos, M.; Macedo, Sofia; Fernandes, Margarida Sá; Pestana, Ana; Pardal, Joana; Batısta, Rui; Vinagre, João; Sanches, Arthur Carniato; Baptista, Armando; Lopes, José Manuel; Soares, Paula

doi:10.1016/j.jaad.2018.08.032

Cited by 33 publications

(29 citation statements)

References 31 publications

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“…In addition, certain molecular biomarkers, including tumor protein 53, cyclin-dependent kinase inhibitor 2A, telomerase reverse transcriptase gene (TERT) and programmed cell death ligand 1 (PD-L1) have been considered as potential factors involved in cSCC progression. In particular, TERT promoter mutations and increased PD-L1 expression have been considered as molecular risk factors for cSCC recurrence (7)(8)(9). However, these predictive risk factors are inadequate to properly assess the recurrence risk of cSCC with high reproducibility and reliability (5,6).…”

Section: Axin2 and Snail Expression Predict The Risk Of Recurrence Inmentioning

confidence: 99%

AXIN2 and SNAIL expression predict the risk of recurrence in cutaneous squamous cell carcinoma after Mohs micrographic surgery

et al. 2020

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Recurrence is a common complication observed during cutaneous squamous cell carcinoma (cSCC) treatment; however, biomarkers for predicting recurrence in cSCC remain unknown. The present study aimed to investigate the predictive value of axis inhibition protein 2 (AXIN2) and SNAIL expression in cSCC recurrence. AXIN2 and SNAIL expression was evaluated using immunohistochemistry in 111 cSCC tissue samples obtained from 18 patients who presented recurrence (recurrence interval, 1-91 months) and 93 patients who did not experience recurrence following Mohs micrographic surgery (MMS) during the follow-up period (156 months). Nomogram construction was performed using patients' clinicopathological characteristics and AXIN2 and SNAIL protein expression. The results demonstrated that high AXIN2 (histoscore >100) and SNAIL (histoscore >100) expression was detected in 35 and 44 cSCC tissues, respectively. Furthermore, the expression levels of AXIN2 and SNAIL were significantly associated in patients with cSCC (P=0.001). AXIN2 and SNAIL expression levels were significantly associated with tumor size (P=0.021 and P=0.044, respectively) and recurrence of cSCC (P=0.017 and P=0.042, respectively). In addition, the results of the Kaplan-Meier curve analysis revealed that recurrence-free survival was significantly associated with tumor size (P=0.025), differentiation status (P<0.001), AXIN2 expression (P=0.001) and SNAIL expression (P=0.001). Furthermore, the results of the multivariate analysis demonstrated that age (P=0.043), AXIN2 expression (P=0.001) and SNAIL expression (P=0.045) were independent risk factors for cSCC recurrence in the present cohort. A nomogram for predicting the 1-, 2-, 3-, and 5-year recurrence-free survival was developed for patients with cSCC by including independent risk factors with a concordance index of 0.75. The results suggested that high AXIN2 and SNAIL expression may be considered as potential risk factors for cSCC recurrence. This nomogram may therefore be useful to assess the probability of recurrence in patients with cSCC following MMS.

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Section: Axin2 and Snail Expression Predict The Risk Of Recurrence Inmentioning

confidence: 99%

AXIN2 and SNAIL expression predict the risk of recurrence in cutaneous squamous cell carcinoma after Mohs micrographic surgery

et al. 2020

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“…Only clinicopathological prognostic markers have been reported in cSCC for recurrence (tumor thickness > 2 mm and >6 mm, invasion beyond subcutaneous fat, perineural invasion, tumor size > 2 cm, and poor differentiation and location in the temple) and metastasis (tumor thickness > 2 mm and >6 mm, invasion beyond subcutaneous fat, perineural invasion, tumor size > 2 cm, poor differentiation, immunosuppression, and location in the temple, lip, and ear) [ 11 ]. We recently reported the association of TERT promoter mutations with worse prognosis (recurrence and metastasis) but we admit that its putative prognostic significance still needs to be established in larger series [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas

Campos

Macedo

Fernandes

et al. 2020

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TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients’ risk stratification.

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“…Statistics show that C228T is somewhat more prevalent than the C250T mutation [ Table 1] in a wide range of cancer types, including various subtypes of CNS cancers, urogenital cancers, melanoma and thyroid cancer [25,26,[28][29][30][31][32][33][34][35][36][37] . Overall, it is widely accepted that glioma, melanoma, bladder cancer and HCC are among those commonlyaffected by TERT promoter mutations [25,28,38] .…”

Section: Tert Promoter Mutations In Several Cancersmentioning

confidence: 99%

Telomerase reverse transcriptase promoter mutations in hepatocellular carcinogenesis

Ma¹,

Yang²,

Li³

et al. 2019

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Through several studies exploiting next-generation sequencing, we are obtaining a clearer picture of the complex genetic and molecular landscape of hepatocellular carcinoma (HCC). Consistent with the findings of other cancer types, telomerase reverse transcriptase (TERT) promoter mutations have been frequently reported in HCC. C228T and C250T are two major types of hot spot mutations in the TERT promoter region. Besides, in hepatitis B virus (HBV)-related HCC cases, the TERT promoter is recurrently interrupted by integration of HBV DNA. TERT promoter mutations are thought to be an early event in HCC carcinogenesis, and they are significantly associated with disease progression. In this review, we provide an updated overview of the somatic mutations in the TERT promoter region and discuss their possible roles in the development of HCC.

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TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma

Cited by 33 publications

References 31 publications

AXIN2 and SNAIL expression predict the risk of recurrence in cutaneous squamous cell carcinoma after Mohs micrographic surgery

AXIN2 and SNAIL expression predict the risk of recurrence in cutaneous squamous cell carcinoma after Mohs micrographic surgery

Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas

Telomerase reverse transcriptase promoter mutations in hepatocellular carcinogenesis

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