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Clinical validation of a prognostic 11-gene expression profiling score in prospectively collected FFPE tissue of patients with AJCC v8 stage II cutaneous melanoma.

前瞻性收集AJCC v8 ⅱ 期皮肤黑色素瘤患者FFPE组织中预后 11 基因表达谱评分的临床验证。

  • 影响因子:6.15
  • DOI:10.1016/j.ejca.2019.10.027
  • 作者列表:"Amaral TMS","Hoffmann MC","Sinnberg T","Niessner H","Sülberg H","Eigentler TK","Garbe C
  • 发表时间:2020-01-01

BACKGROUND:Adjuvant therapies have been approved for patients with AJCC (American Joint Committee on Cancer) stage III and stage IV cutaneous melanoma (CM) after complete resection. These therapies might also be indicated for patients with high-risk stage II CM. MATERIAL AND METHODS:We included patients diagnosed with stage II melanoma between 2000 and 2016 and for which primary tumour tissue was available. The prognostic value of the 11-gene expression profiling score (GEPS) was evaluated as a dichotomized parameter (GEPS ≤0 vs. >0). Endpoints of the analysis were melanoma specific survival (MSS), distant metastasis-free survival (DMFS) and relapse-free survival (RFS). RESULTS:GEPS was determined in 245 patients ranging between -0.7 and 3.53. A total of 111 females and 134 males were included; the median follow-up was 41 months. Kaplan Meier analyses showed statistically significant survival differences between patients with high GEPS (n = 154) and low GEPS (n = 91) for MSS (p = 0.018), DMFS (p = 0.005) and RFS (p = 0.009). The 5-year and 10-year MSS was 92% in the low-GEPS and 82% and 67% in the high-GEPS group, respectively. Multivariate Cox regression analysis showed independent significance for MSS of GEPS (HR = 1.55; p = 0.006), tumor thickness (HR = 1.21; p < 0.001) and age (HR1.05; p = 0.002). CONCLUSION:GEPS was validated as independent prognostic factor for MSS in stage II CM and could be used for therapeutic decisions when systemic therapies become available in stage II CM.


背景: AJCC (美国癌症联合委员会) III期和IV期皮肤黑色素瘤 (CM) 患者完全切除后的辅助治疗已被批准。这些治疗也可能适用于高危II期CM患者。 材料和方法: 我们纳入了 2000 年至 2016 年间诊断为II期黑色素瘤且可获得原发肿瘤组织的患者。将 11 基因表达谱评分 (GEPS) 的预后价值评价为二分参数 (GEPS ≤ 0 vs. >0)。分析的终点是黑色素瘤特异性生存期 (MSS) 、无远处转移生存期 (DMFS) 和无复发生存期 (RFS)。 结果: 在 245 例患者中测定了GEPS,范围在-0.7 和 3.53 之间。共纳入 111 例女性和 134 例男性; 中位随访时间为 41 个月。Kaplan Meier分析显示MSS (p = 154) 、DMFS (p = 0.018) 的高GEPS (n = 0.005) 和低GEPS (n = 91) 患者之间的生存差异有统计学意义和RFS (p = 0.009)。低GEPS组 5 年和 10 年MSS分别为 92%,高GEPS组分别为 82% 和 67%。多因素Cox回归分析显示,GEPS的MSS (HR = 1.55; p = 0.006) 、肿瘤厚度 (HR = 1.21; p < 0.001) 和年龄 (HR1.05; p = 0.002)。 结论: GEPS被验证为II期CM MSS的独立预后因素,可用于II期CM全身治疗时的治疗决策。



作者列表:["Zhang B","Li L","Zhang N","Zhao M","Liu Y","Wei L","Ma L","Xu Z"]

METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.

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作者列表:["Pham CT","Juhasz M","Sung CT","Mesinkovska NA"]

METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.

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作者列表:["Lang UE","Love NR","Cheung C","McCalmont TH","Kim J"]

METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.

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