探讨子宫癌肉瘤中的生物标志物和预后因素：对 L1CAM、CDX2、p53 和 MSI 状态的深入了解。
Exploring biomarkers and prognostic factors in uterine carcinosarcoma: An insight into L1CAM, CDX2, p53, and MSI status.
机构信息
Division of Clinical Research and Technological Development, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
Division of Pathology, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
出版信息
PLoS One. 2023 May 18;18(5):e0285447. doi: 10.1371/journal.pone.0285447. eCollection 2023.
BACKGROUND
Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers.
METHODS AND FINDINGS
The internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively).
CONCLUSION
The strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival.
背景
子宫癌肉瘤（UCS）是一种罕见的癌症，由高级癌性和肉瘤性成分混合组成。UCS 的临床病理预后因素已得到充分确立，但在这种罕见疾病中研究生物标志物影响的研究很少。本研究的目的是使用免疫组织化学特征评估四种标志物的一组突出生物标志物在子宫癌肉瘤（UCS）中的流行程度和预后影响。
方法和发现
仔细探索了巴西一个机构的内部数据库，以选择 2012 年 1 月至 2017 年 12 月期间接受手术和术后卡铂和紫杉醇化疗的 UCS 女性患者。使用免疫组织化学评估包含 UCS 样本的组织微阵列的 L1CAM、CDX2、p53 和微卫星不稳定性标志物。共纳入 57 例患者。平均年龄为 65.3 岁（标准差 7.0）。L1CAM 阴性（评分 0，无染色）者 27 例（47.4%）。在 L1CAM 阳性者中，10 例（17.5%）为弱阳性（评分 1，<10%），6 例（10.5%）为中度阳性（评分 2，10-50%），14 例（24.6%）为强阳性 L1CAM 染色（评分 3，≧50%）。3 例（5.3%）发生 dMMR。15 例（26.3%）肿瘤中 p53 异常表达。3 例（5.3%）患者 CDX2 阳性。研究人群的 3 年无进展生存率（PFS）为 21.2%（95%CI：11.7-38.1），3 年总生存率（OS）为 29.4%（95%CI：18.1-47.6）。多变量分析显示，存在转移和 CDX2 阳性与较差的 PFS（p<0.001 和 p=0.002）和 OS（p<0.001 和 p=0.009）显著相关。
结论
CDX2 对预后的强烈影响需要进一步研究。生物学或分子变异性可能会影响其他标志物对生存影响的评估。
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