使用全幅数字成像技术对高级别浆液性卵巢癌进行组织病理学亚型分类。
Histopathological subtyping of high-grade serous ovarian cancer using whole slide imaging.
发表日期:2023 Feb 10
作者:
Chiho Miyagawa, Hidekatsu Nakai, Tomoyuki Otani, Ryusuke Murakami, Shiki Takamura, Hisamitsu Takaya, Kosuke Murakami, Masaki Mandai, Noriomi Matsumura
来源:
Journal of Gynecologic Oncology
摘要:
我们已经建立了4种组织病理学亚型来分类高级别浆膜性卵巢癌(HGSOC),并报告了间叶转化(MT)亚型比其他亚型具有更差的预后。在本研究中,我们修改了组织病理学亚型算法,以实现全幻灯片成像(WSI)中的高观察者一致性,并对MT类型的肿瘤生物学进行表征,以个体化治疗。
四位观察者使用The Cancer Genome Atlas数据中的HGSOC WSI进行了组织病理学分类。作为验证集,来自Kindai和京都大学的病例由4位观察者独立评价以确定一致性率。此外,还通过基因本体术语分析检查MT类型中高表达的基因。还进行了免疫组织化学研究以验证通路分析。
修改算法后,表明4种分类的kappa系数,指示观察者一致性,在两种分类(MT vs. non-MT)中都大于0.5(中等一致性)和大于0.7(实质一致性)。基因表达分析显示,与血管生成和免疫反应有关的基因本体术语富集于高度表达于MT类型中的基因。CD31阳性微血管密度在MT类型中比非MT类型更高,并观察到具有CD8 / CD103阳性免疫细胞高浸润的肿瘤组在MT类型中。
我们开发了一种算法来对HGSOC进行可重复的组织病理学亚型分类,并使用WSI。本研究的结果可用于HGSOC的个体化治疗,包括抗血管生成和免疫治疗。 © 2023.亚洲妇科肿瘤学会,韩国妇科肿瘤学会和日本妇科肿瘤学会。
We have established 4 histopathologic subtyping of high-grade serous ovarian cancer (HGSOC) and reported that the mesenchymal transition (MT) type has a worse prognosis than the other subtypes. In this study, we modified the histopathologic subtyping algorithm to achieve high interobserver agreement in whole slide imaging (WSI) and to characterize the tumor biology of MT type for treatment individualization.Four observers performed histopathological subtyping using WSI of HGSOC in The Cancer Genome Atlas data. As a validation set, cases from Kindai and Kyoto Universities were independently evaluated by the 4 observers to determine concordance rates. In addition, genes highly expressed in MT type were examined by gene ontology term analysis. Immunohistochemistry was also performed to validate the pathway analysis.After algorithm modification, the kappa coefficient, which indicates interobserver agreement, was greater than 0.5 (moderate agreement) for the 4 classifications and greater than 0.7 (substantial agreement) for the 2 classifications (MT vs. non-MT). Gene expression analysis showed that gene ontology terms related to angiogenesis and immune response were enriched in the genes highly expressed in the MT type. CD31 positive microvessel density was higher in the MT type compared to the non-MT type, and tumor groups with high infiltration of CD8/CD103 positive immune cells were observed in the MT type.We developed an algorithm for reproducible histopathologic subtyping classification of HGSOC using WSI. The results of this study may be useful for treatment individualization of HGSOC, including angiogenesis inhibitors and immunotherapy.© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.