Michalova Kvetoslava, Strakova-Peterikova Andrea, Ondic Ondrej, Vanecek Tomas, Michal Michael, Hejhalova Nikola, Holub Petr, Slavik Petr, Hluchy Adam, Gettse Polina, Daum Ondrej, Svajdler Marian, Michal Michal, Presl Jiri
Department of Pathology, Faculty of Medicine in Plzen, University Hospital Plzen, Charles University, Plzen, Czech Republic.
Biopticka Laboratory, Ltd, Plzen, Czech Republic.
Virchows Arch. 2024 Dec 15. doi: 10.1007/s00428-024-03996-1.
Molecular classification of endometrial carcinomas (EC) divides these neoplasms into four distinct subgroups based on their molecular background. Given its clinical significance, genetic examination is becoming integral to the diagnostic process. This study aims to share our experience with the molecular classification of EC using immunohistochemistry (IHC) and next-generation sequencing (NGS). We included all ECs diagnosed at two institutions from 2020 to the present. All cases were prospectively examined by IHC for MMR proteins and p53, followed by NGS using a customized panel covering 18 genes, based on which ECs were classified into four molecular subgroups: POLE mutated, hypermutated (MMR deficient), no specific molecular profile (NSMP), and TP53 mutated. The cohort comprised 270 molecularly classified ECs: 18 (6.6%) POLE mutated, 85 (31.5%) hypermutated, 137 (50.7%) NSMP, and 30 (11.1%) TP53 mutated. Twelve cases (4.4%) were classified as 'multiple classifier' EC. Notably, most of these cases with available follow-up (6/9) behaved aggressively. Within the POLEmut EC group, 3/4 cases had advanced tumors, including one patient who died of the disease. Similarly, in the MMRd/TP53mut group, 3/5 patients with available follow-up had metastatic disease, leading to death of the patient in 1 case. ECs of NSMP showed multiple genetic alterations, with the most common mutations being PTEN (44% within the group of NSMP), followed by PIK3CA (30%), ARID1A (21%), and KRAS (9%). Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.
子宫内膜癌（EC）的分子分类根据其分子背景将这些肿瘤分为四个不同的亚组。鉴于其临床意义，基因检测正成为诊断过程中不可或缺的一部分。本研究旨在分享我们使用免疫组织化学（IHC）和二代测序（NGS）对EC进行分子分类的经验。我们纳入了2020年至今在两家机构诊断的所有EC病例。所有病例均先通过IHC对MMR蛋白和p53进行前瞻性检测，然后使用覆盖18个基因的定制panel进行NGS检测，据此将EC分为四个分子亚组：POLE突变型、高突变型（MMR缺陷型）、无特定分子特征（NSMP）型和TP53突变型。该队列包括270例经分子分类的EC：18例（6.6%）为POLE突变型，85例（31.5%）为高突变型，137例（50.7%）为NSMP型，30例（11.1%）为TP53突变型。12例（4.4%）病例被分类为“多重分类器”EC。值得注意的是，这些有可用随访信息的病例中，大多数（6/9）表现为侵袭性。在POLEmut EC组中，3/4的病例为晚期肿瘤，其中1例患者死于该疾病。同样，在MMRd/TP53mut组中，有可用随访信息的3/5患者发生了转移性疾病，导致1例患者死亡。NSMP型EC显示出多种基因改变，最常见的突变是PTEN（在NSMP组中占44%），其次是PIK3CA（30%）、ARID1A（21%）和KRAS（9%）。我们的研究结果表明，将免疫组织化学与NGS相结合可以对EC进行更可靠的分类，包括“多重分类器”病例，根据我们的观察，这些病例往往表现出侵袭性行为。此外，我们的数据突出了NSMP型EC复杂的基因背景，这有助于对该组内的肿瘤进行进一步分层，并可能有助于选择患者进行专门的临床试验。
