Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Mod Pathol. 2022 Sep;35(9):1247-1253. doi: 10.1038/s41379-022-01060-4. Epub 2022 Mar 28.
We compared clinicopathologic and molecular features of esophageal squamous cell carcinoma (SCC) with basaloid features to conventional SCC using surgical resections of treatment naïve esophageal carcinomas and cases available from the TCGA database. Twenty-two cases of SCC with basaloid features were identified in the Mass General Brigham pathology archives, including 9 cases with pure basaloid morphology and 13 cases with mixed other features such as conventional well- or poorly differentiated areas or sarcomatoid areas. Thirty-eight cases of conventional SCC matched by tumor stage were used as controls. HPV infection status was tested by p16 immunohistochemistry and HPV mRNA ISH. Digital slides for 94 cases of esophageal SCC from TCGA found in the Genomic Data Commons (GDC) Data Portal were reviewed. Five cases of SCC with basaloid features were identified. Genomic profiles of SCC with basaloid features were compared to the rest of 89 SCCs without basaloid features. In addition, eight tumor sections from six patients selected from our cohort underwent in-house molecular profiling. Compared to conventional SCC, SCC with basaloid features were more frequently associated with diffuse or multifocal squamous dysplasia (p < 0.001). P16 IHC was positive in 2/13 cases, whereas HPV mRNA ISH was negative in 17/17 cases (including both p16-positive cases). SCC with basaloid features and conventional SCC from TCGA showed similar rates of TP53 mutations, CDKN2A/B deletions, and CCDN1 amplifications. TP53 variants were identified in all in-house samples that had sufficient coverage. Survival analyses between SCC with basaloid features versus conventional SCC (matched for tumor stage) did not reveal any statistically significant differences. In conclusion, esophageal SCC with basaloid features has similar survival and genomic alterations to those of conventional SCC, are more frequently associated with diffuse or multifocal dysplasia, and are not associated with HPV (high-risk strains) infection.
我们比较了经手术切除的未经治疗的食管癌和 TCGA 数据库中可用病例的具有基底样特征的食管鳞状细胞癌 (SCC) 与传统 SCC 的临床病理和分子特征。在麻省总医院病理档案中确定了 22 例具有基底样特征的 SCC，包括 9 例具有纯基底样形态和 13 例具有混合其他特征，如传统的高或低分化区域或肉瘤样区域。作为对照，选择了 38 例肿瘤分期匹配的传统 SCC。HPV 感染状态通过 p16 免疫组化和 HPV mRNA ISH 检测。审查了从 GDC 数据门户的 TCGA 发现的 94 例食管 SCC 的数字幻灯片。确定了 5 例具有基底样特征的 SCC。将具有基底样特征的 SCC 的基因组谱与其余 89 例无基底样特征的 SCC 进行比较。此外，从我们的队列中选择了六个患者的八个肿瘤切片进行了内部分子分析。与传统 SCC 相比，具有基底样特征的 SCC 更常与弥漫性或多灶性鳞状发育不良相关 (p<0.001)。13 例中有 2 例 p16 IHC 阳性，而 17 例 HPV mRNA ISH 均为阴性（包括 p16 阳性病例）。TCGA 中的具有基底样特征的 SCC 和传统 SCC 显示出相似的 TP53 突变、CDKN2A/B 缺失和 CCDN1 扩增率。在所有具有足够覆盖度的内部样本中都发现了 TP53 变体。具有基底样特征的 SCC 与传统 SCC（按肿瘤分期匹配）之间的生存分析未显示出任何统计学上的显著差异。总之，具有基底样特征的食管 SCC 与传统 SCC 的生存和基因组改变相似，更常与弥漫性或多灶性发育不良相关，并且与 HPV（高危株）感染无关。
Zotero 插件