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Paired related homeobox 1 (PRRX1) is an inducer of epithelial‐to‐mesenchymal transition (EMT) in different types of cancer cells. We detected low PRRX1 expression in nevus but increased levels in primary human melanoma and cell lines carrying the BRAFV600E mutation. High expression of PRRX1 correlates with invasiveness and enrichment of genes belonging to the EMT programme. Conversely, we found that loss of PRRX1 in metastatic samples is an independent prognostic predictor of poor survival for melanoma patients. Here, we show that stable depletion of PRRX1 improves the growth of melanoma xenografts and increases the number of distant spontaneous metastases, compared to controls. We provide evidence that loss of PRRX1 counteracts the EMT phenotype, impairing the expression of other EMT‐related transcription factors, causing dysregulation of the ERK and signal transducer and activator of transcription 3 (STAT3) signaling pathways, and abrogating the invasive and migratory properties of melanoma cells while triggering the up‐regulation of proliferative/melanocytic genes and the expression of the neural‐crest‐like markers nerve growth factor receptor (NGFR; also known as neurotrophin receptor p75NTR) and neural cell adhesion molecule L1 (L1CAM). Overall, our results indicate that loss of PRRX1 triggers a switch in the invasive programme, and cells de‐differentiate towards a neural crest stem cell (NCSC)‐like phenotype that accounts for the metastatic aggressiveness. [ABSTRACT FROM AUTHOR]

Satellitosis or in-transit metastasis (S-ITM) has clinical outcomes comparable to node-positivity in cutaneous squamous cell carcinoma (cSCC). There is a need to stratify the risk groups. To determine which prognostic factors of S-ITM confer an increased risk of relapse and cSCC-specific–death. A retrospective, multicenter cohort study. Patients with cSCC developing S-ITM were included. Multivariate competing risk analysis evaluated which factors were associated with relapse and specific death. Of a total of 111 patients with cSCC and S-ITM, 86 patients were included for analysis. An S-ITM size of ≥20 mm, >5 S-ITM lesions, and a primary tumor deep invasion was associated with an increased cumulative incidence of relapse (subhazard ratio [SHR]: 2.89 [95% CI, 1.44-5.83; P =.003], 2.32 [95% CI, 1.13-4.77; P =.021], and 2.863 [95% CI, 1.25-6.55; P =.013]), respectively. Several >5 S-ITM lesions were also associated with an increased probability of specific death (SHR: 3.48 [95% CI, 1.18-10.2; P =.023]). Retrospective study and heterogeneity of treatments. The size and the number of S-ITM lesions confer an increased risk of relapse and the number of S-ITM an increased risk of specific-death in patients with cSCC presenting with S-ITM. These results provide new prognostic information and can be considered in the staging guidelines. [ABSTRACT FROM AUTHOR]

Background: There is limited information on microsatellite survival outcomes in patients with melanoma.Objective: To evaluate survival outcomes in patients with microsatellites, assess their role within stage III stratification of the American Joint Committee on Cancer classification, and assess the results of sentinel lymph node biopsies in patients with microsatellites.Methods: A retrospective bicenter cohort study from 1998 to 2019 included patients with a diagnosis of invasive cutaneous melanoma.Results: Of a total of 5216 patients, 108 (2.1%) had microsatellites at initial staging. Survival analysis showed that microsatellites were an independent risk factor with decreased overall survival (OS), melanoma-specific survival (MSS), and disease-free survival, with hazard ratios of 1.57, 1.76, and 1.76, respectively. Stratified analysis in patients with stage III melanoma showed a 5-year OS of 35% (95% CI, 17.3%-73.4%) and a MSS of 45% (95% CI, 23.1-87.5) for patients with stage IIIB melanoma with microsatellites.Limitations: Retrospective design of the study.Conclusion: Microsatellites were associated with other adverse melanoma prognostic factors. A multivariate Cox regression analysis showed that they are an independent risk factor for worse OS, MSS, and disease-free survival. Patients with stage IIIB melanoma with microsatellites had worse OS and MSS, whereas patients with stage IIIC melanoma had worse OS but not MSS. [ABSTRACT FROM AUTHOR]

Background: Many patients with low-stage cutaneous melanoma will experience tumor recurrence, metastasis, or death, and many higher staged patients will not.Objective: To develop an algorithm by integrating the 31-gene expression profile test with clinicopathologic data for an optimized, personalized risk of recurrence (integrated 31 risk of recurrence [i31-ROR]) or death and use i31-ROR in conjunction with a previously validated algorithm for precise sentinel lymph node positivity risk estimates (i31-SLNB) for optimized treatment plan decisions.Methods: Cox regression models for ROR were developed (n = 1581) and independently validated (n = 523) on a cohort with stage I-III melanoma. Using National Comprehensive Cancer Network cut points, i31-ROR performance was evaluated using the midpoint survival rates between patients with stage IIA and stage IIB disease as a risk threshold.Results: Patients with a low-risk i31-ROR result had significantly higher 5-year recurrence-free survival (91% vs 45%, P < .001), distant metastasis-free survival (95% vs 53%, P < .001), and melanoma-specific survival (98% vs 73%, P < .001) than patients with a high-risk i31-ROR result. A combined i31-SLNB/ROR analysis identified 44% of patients who could forego sentinel lymph node biopsy while maintaining high survival rates (>98%) or were restratified as being at a higher or lower risk of recurrence or death.Limitations: Multicenter, retrospective study.Conclusion: Integrating clinicopathologic features with the 31-GEP optimizes patient risk stratification compared to clinicopathologic features alone. [ABSTRACT FROM AUTHOR]

There is no consensus on the imaging tests that should be performed at the initial staging of melanoma patients. To evaluate the diagnostic accuracy of 4 imaging studies for the initial staging of melanoma patients. Cross-sectional study with prospectively collected data, from January 2011 to April 2017, including patients with clinical stage T2b to T4b according to 2009 American Joint Committee on Cancer, without evidence of metastasis. Initial staging of 308 patients detected 16.6% of metastases and 5.8% false-positive results, overall. Regional lymph node ultrasonography showed a metastasis detection rate (MDR) of 12.8%, false-positive rate of 0.8%, and accuracy of 96.0%. Computed tomography (CT) and positron emission tomography-CT had the highest detection rates at stage T4b: MDR, 13.3%; false-positive rate, 8.9%; accuracy, 91.1%; and MDR, 6.9%; false-positive rate, 0%; and accuracy, 93.1%, respectively. Brain magnetic resonance imaging showed a MDR of 2.0% in T4b. Single-center study. Performing ultrasound scans for assessing lymph node metastasis in patients with American Joint Committee on Cancer T2b stage and above is advisable. In patients with stage T4b, CT or positron emission tomography-CT are suitable for the detection of metastasis. Brain magnetic resonance imaging at T4b deserves further discussion, considering the ultimate clinical benefit in management and therapeutic options for asymptomatic patients. [ABSTRACT FROM AUTHOR]

Background: There is no international consensus on optimal follow-up schedules and which supplementary tests should be used after resection of a primary melanoma.Objective: We sought to analyze the performance of the follow-up components and identify procedures that detect melanoma metastasis earlier.Methods: This was a prospective cohort from 290 consecutive patients given a diagnosis of stage IIB, IIC, and III melanoma. Patients were followed up with an intensive protocol based on imaging studies (computed tomography of the chest, abdomen, and pelvis, and brain magnetic resonance imaging), periodic laboratory tests, regular physical examinations, and patient self-examinations.Results: A total of 2382 clinical examinations and 3069 imaging tests were performed. The patients completed 899.8 person-years of follow-up, with a median of 2.5 years. In all, 115 recurrences in 290 patients were recorded, of which computed tomography detected 48.3%; brain magnetic resonance imaging, 7.6%; laboratory test, 2.5%; physician, 23.7%; and patient, 17.8%.Limitations: Patients with stage III melanoma were not systematically classified into subgroups and overall survival was not evaluated.Conclusion: We observed that this intensive monitoring is appropriate for early detection of recurrence in stage IIB, IIC, and III melanoma. Prompt diagnosis of metastasis and the recent development of new therapeutic targets may improve overall survival. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the imaging tests that should be performed at the initial staging of melanoma patients.Objective: To evaluate the diagnostic accuracy of 4 imaging studies for the initial staging of melanoma patients.Methods: Cross-sectional study with prospectively collected data, from January 2011 to April 2017, including patients with clinical stage T2b to T4b according to 2009 American Joint Committee on Cancer, without evidence of metastasis.Results: Initial staging of 308 patients detected 16.6% of metastases and 5.8% false-positive results, overall. Regional lymph node ultrasonography showed a metastasis detection rate (MDR) of 12.8%, false-positive rate of 0.8%, and accuracy of 96.0%. Computed tomography (CT) and positron emission tomography-CT had the highest detection rates at stage T4b: MDR, 13.3%; false-positive rate, 8.9%; accuracy, 91.1%; and MDR, 6.9%; false-positive rate, 0%; and accuracy, 93.1%, respectively. Brain magnetic resonance imaging showed a MDR of 2.0% in T4b.Limitations: Single-center study.Conclusion: Performing ultrasound scans for assessing lymph node metastasis in patients with American Joint Committee on Cancer T2b stage and above is advisable. In patients with stage T4b, CT or positron emission tomography-CT are suitable for the detection of metastasis. Brain magnetic resonance imaging at T4b deserves further discussion, considering the ultimate clinical benefit in management and therapeutic options for asymptomatic patients. [ABSTRACT FROM AUTHOR]