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High-grade Serous Carcinoma Occurring in a Serous Cystadenoma on the Background of a Serous Tubal Intraepithelial Carcinoma (STIC)-like Lesion: A Case Report With Literature Review. 在浆液性输卵管上皮内瘤(STIC)样病变背景下发生于浆液性囊腺瘤的高级别浆液性癌:病例报告与文献综述。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-04-18 DOI: 10.1097/PGP.0000000000001018
Filipp Vladimirovich Novikov, Aleksandr Grigorevich Anufriev, Gennadii Dmitrievich Efremov

At present, the prevailing concept is that high-grade serous carcinoma (HGSC) arises from the fallopian tubes (FTs). We report an HGSC case occurring in a serous ovarian cyst against the background of a serous tubal intraepithelial carcinoma (STIC)-like lesion. We also provide a literature review that contains references to clinical cases of the occurrence of STIC-like lesions in the ovary and phylogenetic studies that do not always reveal obvious bonds between early dysplastic serous lesions and HGSC. The article discusses cases of association between HGSCs of serous borderline tumors (SBTs) and low-grade serous carcinomas (LGSCs) in the context of their possible histogenetic relationship. We propose a concept in which high-grade serous carcinogenesis, represented by the p53-signature-STIC-HGSC continuity, occurs in the serous epithelium of both the FT and other locations.

目前,流行的观点是高级别浆液性癌(HGSC)来源于输卵管。我们报告了一个发生在浆液性卵巢囊肿中的 HGSC 病例,其背景是浆液性输卵管上皮内癌(STIC)样病变。我们还提供了一篇文献综述,其中包括卵巢STIC样病变的临床病例和系统发育研究的参考文献,这些研究并不总能揭示早期浆液性病变发育不良与HGSC之间的明显联系。文章讨论了浆液性边界瘤(SBT)的 HGSC 与低级别浆液性癌(LGSC)之间可能存在的组织遗传学关系。我们提出了一种概念,即高级别浆液性癌发生于 FT 和其他部位的浆液性上皮,以 p53 标志-STIC-HGSC 连续性为代表。
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引用次数: 0
Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study. 结直肠癌/血管内皮生长因子信号通路中的内皮素-1/Deleted在胎盘早剥谱发病机制中的可能作用:病例对照研究。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-01-29 DOI: 10.1097/PGP.0000000000001017
Dalia M Badary, Huda Elsaied, Mahmoud R Abdel-Fadeil, Mohammed K Ali, Hisham Abou-Taleb, Heba M Iraqy

Summary: Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

摘要:Netrin-1 是一种上皮分泌的蛋白质,通过促进细胞母细胞增殖和胎盘血管发育,在胎盘形成过程中发挥关键作用。这些作用是通过几种受体介导的,包括大肠癌(DCC)受体。胎盘早剥谱系(PAS)是滋养细胞侵入子宫肌层的一种夸张现象。确切的病因尚不清楚,但据认为滋养细胞侵袭增加、蜕膜化缺陷和/或血管生成异常可能是其中的一个原因。我们的研究旨在探讨巨噬细胞诱导的网织蛋白-1/DCC/血管内皮生长因子(VEGF)信号传导在PAS发病机制中的作用。研究共纳入了 29 名 PAS 孕妇(作为病例)和 29 名正常妊娠孕妇(作为对照)。分娩时,收集并处理两组孕妇的胎盘组织,通过酶联免疫测定技术评估胎盘净蛋白-1的水平,并对组织DCC受体进行免疫组化分析。PAS病例的胎盘组织网织蛋白-1水平明显高于正常组,差异有统计学意义。与正常胎盘相比,PAS 病例中的 DCC 受体、血管内皮生长因子和巨噬细胞募集均明显过表达。巨噬细胞诱导的netrin-1/DCC/VEGF信号可能通过增强滋养细胞血管生成参与了PAS的发病机制。
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引用次数: 0
Clinical Significance of Tumor Immune Microenvironment in Endometrial Endometrioid Carcinoma, Grade 1 With DNA Mismatch Repair Protein Loss. 具有 DNA 错配修复蛋白缺失的 1 级子宫内膜样癌肿瘤免疫微环境的临床意义
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-01-22 DOI: 10.1097/PGP.0000000000001020
Kazuhisa Hachisuga, Minoru Kawakami, Hiroshi Tomonobe, Shoji Maenohara, Keisuke Kodama, Hiroshi Yagi, Masafumi Yasunaga, Ichiro Onoyama, Kazuo Asanoma, Hideaki Yahata, Yoshinao Oda, Kiyoko Kato

The administration of immune checkpoint inhibitors (ICIs) is increasing in endometrial cancer, especially in the mismatch repair (MMR)-deficient group. To prevent unnecessary immune-related adverse events, ICIs need to be administered to more appropriate patients. The tumor immune microenvironment has been reported to be a predictive marker of the efficacy of ICI therapies. This study evaluated CD8, FoxP3, CD68, PD-L1, and β-catenin expression in endometrial endometrioid carcinoma, grade 1 (G1) with DNA mismatch repair protein loss (MMR loss), and their association with clinicopathological features. We retrospectively analyzed tumor samples from 107 patients with endometrial endometrioid carcinoma, G1 (MMR-deficient group: n=67; MMR-proficient group: n=40). Overall, 47 cases of MLH1/PMS2 loss and 20 cases of MSH2/MSH6 loss were observed. The patients with low intraepithelial CD8 expression significantly more frequently exhibited deep myometrial invasion, and the elderly group (≥60 y) significantly more frequently showed low stromal CD8 expression. In addition, FoxP3-positive cell count and FoxP3/CD8+ ratio were significantly correlated with the International Federation of Obstetrics and Gynecology 2023 stage and lymph node metastasis. In the Kaplan-Meier analysis, the patients with low intraepithelial or stromal CD8 expression had shorter progression-free survival (PFS) than those with high intraepithelial or stromal CD8 expression, albeit not significantly. We clarified that the tumor immune microenvironment had an impact on clinicopathological features within the group with MMR loss, which is the main target for ICIs, limited to endometrioid carcinoma, G1. Further studies are needed, including on patients administered ICIs.

在子宫内膜癌中,尤其是在错配修复(MMR)缺陷组中,使用免疫检查点抑制剂(ICIs)的情况越来越多。为了防止不必要的免疫相关不良事件,需要对更合适的患者使用 ICIs。据报道,肿瘤免疫微环境是 ICI 疗效的预测指标。本研究评估了具有DNA错配修复蛋白缺失(MMR缺失)的1级(G1)子宫内膜样癌中CD8、FoxP3、CD68、PD-L1和β-catenin的表达及其与临床病理特征的关系。我们回顾性分析了107例G1级子宫内膜样癌患者的肿瘤样本(MMR缺失组:n=67;MMR良好组:n=40)。总计观察到 47 例 MLH1/PMS2 缺失和 20 例 MSH2/MSH6 缺失。上皮内 CD8 低表达的患者明显更多表现为子宫肌层深部浸润,老年组(≥60 岁)明显更多表现为基质 CD8 低表达。此外,FoxP3阳性细胞数和FoxP3/CD8+比值与国际妇产科联盟2023分期和淋巴结转移显著相关。在 Kaplan-Meier 分析中,上皮内或基质 CD8 低表达患者的无进展生存期(PFS)短于上皮内或基质 CD8 高表达患者,尽管差异不明显。我们明确了肿瘤免疫微环境对MMR缺失组临床病理特征的影响,而MMR缺失是ICIs的主要靶点,仅限于子宫内膜样癌G1。还需要进一步研究,包括对使用 ICIs 的患者进行研究。
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引用次数: 0
Molecular Surrogate Subtypes of Ovarian and Peritoneal Low-grade Serous Carcinoma. 卵巢癌和腹膜低级别浆液性癌的分子替代亚型
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-10 DOI: 10.1097/PGP.0000000000001043
Annalyn Da-Anoy, Eun Young Kang, Cheng Han Lee, Dane Cheasley, Marta Llaurado Fernandez, Mark S Carey, Anna Cameron, Martin Köbel

Low-grade serous carcinoma (LGSC) is an uncommon histotype of ovarian carcinoma, accounting for ~3% of cases. There is evidence that survival of peritoneal LGSC (pLGSC) is longer than that of ovarian LGSC (oLGSC). Key molecular alterations of LGSC have been established, including loss of CDKN2A and PR expression, MAPK pathway alterations, and loss of USP9X expression. We hypothesized that LGSC could be subclassified into clinically applicable molecular subtypes by a few surrogate tests similar to endometrioid carcinomas using a hierarchical decision tree based on the strength of the prognostic associations of the individual alterations. Our study included 71 LGSCs. Immunohistochemistry for CDKN2A, ER, PR, NF1, and USP9X and sequencing for KRAS , NRAS , and BRAF were performed. Our data showed the co-occurrence of key molecular alterations, and despite suggestive trends, hierarchical molecular subtyping did not provide significantly different stratification of patients according to survival in this cohort. We confirmed that patients diagnosed with pLGSC have a longer survival than high-stage oLGSC, with the intriguing observation that normal CDKN2A and PR status were associated with excellent survival in pLGSC. Therefore, CDKN2A and PR status might aid in the classification of indeterminate implants, where abnormal findings favor pLGSC over noninvasive implants. Molecular subtypes should be further evaluated in larger cohorts for their prognostic and potentially predictive value.

低级别浆液性癌(LGSC)是一种不常见的卵巢癌组织类型,约占病例的3%。有证据表明,腹膜低级别浆液性癌(pLGSC)的生存期长于卵巢低级别浆液性癌(oLGSC)。LGSC的关键分子改变已经确定,包括CDKN2A和PR表达缺失、MAPK通路改变和USP9X表达缺失。我们假设,可以通过一些类似于子宫内膜样癌的替代检测,根据单个改变的预后关联强度,使用分层决策树将 LGSC 亚分类为临床适用的分子亚型。我们的研究包括 71 例 LGSCs。对 CDKN2A、ER、PR、NF1 和 USP9X 进行了免疫组化,并对 KRAS、NRAS 和 BRAF 进行了测序。我们的数据显示了关键分子改变的共同发生,尽管有提示性趋势,但分子亚型的分层并不能根据患者的生存情况对其进行明显的分层。我们证实,确诊为 pLGSC 的患者比高期 oLGSC 患者的生存期更长,同时发现一个有趣的现象,即 CDKN2A 和 PR 正常与 pLGSC 患者的良好生存期相关。因此,CDKN2A和PR状态可能有助于对不确定的种植体进行分类,在不确定的种植体中,异常结果更倾向于pLGSC而非非浸润性种植体。分子亚型应在更大的队列中进一步评估其预后和潜在的预测价值。
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引用次数: 0
SOX17 Expression in Mesotheliomas and Benign Mesothelial Proliferations: Implications for Differential Diagnosis With Gynecologic Carcinomas. 间皮瘤和良性间皮增生中的 SOX17 表达:与妇科癌鉴别诊断的意义。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-31 DOI: 10.1097/PGP.0000000000001076
Natthawadee Laokulrath, Yin P Hung, Jaclyn C Watkins, Esther Oliva, Kyle M Devins

SOX17 has recently emerged as a novel immunohistochemical marker for cancers of endometrial and ovarian origin with improved specificity compared with the widely used Mullerian marker PAX8. However, evaluation of SOX17 in benign and malignant peritoneal mesothelial proliferations remains limited, and these may mimic gynecologic carcinomas, particularly on small biopsies. We evaluated SOX17 and PAX8 expression in 20 benign mesothelial lesions (5 adenomatoid tumors, 5 well-differentiated papillary mesothelial tumors, and 10 peritoneal inclusion cysts) and 16 epithelioid peritoneal mesotheliomas. The 17 female and 3 male patients with benign mesothelial lesions ranged from 20 to 80 yr (median: 56.5 yr), while the 9 females and 7 males with mesothelioma ranged from 47 to 85 yr (median: 57.5 yr). SOX17 was positive in 5 (25%) benign lesions (2 adenomatoid tumors, 3 peritoneal inclusion cysts) and 2 (13%) mesotheliomas, while PAX8 stained 8 (40%) benign lesions (1 adenomatoid tumor, 1 well-differentiated papillary mesothelial tumor, 6 peritoneal inclusion cysts), and 2 (13%) mesotheliomas. Results for the 2 stains showed incomplete concordance, with agreement in 15 (75%) benign proliferations and 14 (88%) mesotheliomas. Our findings suggest that SOX17 positivity alone is insufficient to confirm a diagnosis of gynecologic carcinoma over a mesothelial proliferation and pathologists should exercise caution when these entities are diagnostic considerations.

最近,SOX17 成为子宫内膜癌和卵巢癌的新型免疫组化标记物,与广泛使用的穆勒氏标记物 PAX8 相比,其特异性更高。然而,对良性和恶性腹膜间皮增生中 SOX17 的评估仍然有限,这些增生可能会模拟妇科癌,尤其是在小活检中。我们评估了 20 个良性间皮病变(5 个腺瘤、5 个分化良好的乳头状间皮瘤和 10 个腹膜包涵囊肿)和 16 个上皮样腹膜间皮瘤中 SOX17 和 PAX8 的表达。17名女性和3名男性良性间皮病变患者的年龄介于20至80岁之间(中位数:56.5岁),而9名女性和7名男性间皮瘤患者的年龄介于47至85岁之间(中位数:57.5岁)。5例(25%)良性病变(2例腺瘤、3例腹膜包涵囊肿)和2例(13%)间皮瘤的SOX17呈阳性,而8例(40%)良性病变(1例腺瘤、1例分化良好的乳头状间皮瘤、6例腹膜包涵囊肿)和2例(13%)间皮瘤的PAX8染色呈阳性。两种染色的结果显示不完全一致,15 例(75%)良性增生和 14 例(88%)间皮瘤的染色结果一致。我们的研究结果表明,单凭SOX17阳性不足以确诊为妇科癌而不是间皮增生,病理学家在诊断这些实体时应谨慎行事。
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引用次数: 0
Role of Immunohistochemical Analysis of p16 and p53 in Vulvar Carcinoma. 外阴癌中 p16 和 p53 免疫组化分析的作用
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-31 DOI: 10.1097/PGP.0000000000001077
Matthias Choschzick, Andre Gut, Ladina Hoesli, Cristina Stergiou

Tumor human papillomavirus (HPV) status is an important prognostic factor in vulvar cancer as indicated in the latest WHO classification of female genital tract tumors. Immunohistochemical detection of p16 is well established as a surrogate biomarker for tumor HPV association, including squamous cell carcinomas of the vulva. HPV-independent vulvar carcinomas are heterogeneous with 2 subcategories according to the TP53 mutation status. Therefore, the simultaneous use of p53 and p16 immunohistochemistry is recommended for accurate subclassification of vulvar squamous cell carcinomas. However, the role of molecular analytical tools, in particular RNA ISH and TP53 sequencing, is not so clear. This study aimed to investigate the performance of p53 and p16 immunohistochemistry for the diagnosis of vulvar carcinomas in comparison to TP53 mutation analysis and HPV RNA ISH. We analyzed 48 vulvar carcinomas in a tissue microarray format. Sensitivity and specificity for both methods, p16 (100% and 96%) and p53 (95% and 90%) immunohistochemistry for detection of HPV association as well as for TP53 mutations was high. Combining p16 and p53 immunohistochemistry we correctly classified all carcinomas in our series according to current WHO criteria. The sensitivity of HPV RNA ISH for the detection of HPV association was lower compared to p16 immunohistochemistry. Rare HPV-associated cases with TP53 mutation and HPV-independent tumors with p16 overexpression are discussed. In summary, the combined use of p16 and p53 immunohistochemistry for subclassification of vulvar carcinomas is justified in daily practice. Molecular tests should be restricted to rare cases with ambiguous clinicopathologic or immunohistochemical features.

根据世界卫生组织最新的女性生殖道肿瘤分类,肿瘤人乳头瘤病毒(HPV)状态是外阴癌的一个重要预后因素。免疫组化检测 p16 作为肿瘤 HPV 相关性(包括外阴鳞状细胞癌)的替代生物标志物已得到广泛认可。HPV独立型外阴癌具有异质性,根据TP53突变状态可分为两个亚类。因此,建议同时使用 p53 和 p16 免疫组化对外阴鳞状细胞癌进行准确的亚分类。然而,分子分析工具,特别是 RNA ISH 和 TP53 测序的作用还不是很明确。本研究旨在探讨 p53 和 p16 免疫组化与 TP53 突变分析和 HPV RNA ISH 相比,在外阴癌诊断中的作用。我们以组织芯片格式分析了48例外阴癌。两种方法的灵敏度和特异性都很高,p16(100% 和 96%)和 p53(95% 和 90%)免疫组化检测 HPV 相关性和 TP53 突变。根据目前的世界卫生组织标准,结合 p16 和 p53 免疫组化,我们对系列中的所有癌症进行了正确分类。与 p16 免疫组化相比,HPV RNA ISH 检测 HPV 相关性的灵敏度较低。本文还讨论了罕见的TP53突变的HPV相关病例和p16过表达的HPV非依赖性肿瘤。总之,在日常实践中,联合使用 p16 和 p53 免疫组化对外阴癌进行亚分类是合理的。分子检测应仅限于临床病理或免疫组化特征不明确的罕见病例。
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引用次数: 0
Adenomatoid Tumor Mimicking Peritoneal Carcinomatosis: A Case Report. 模仿腹膜癌肿的腺瘤样肿瘤:病例报告
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-31 DOI: 10.1097/PGP.0000000000001079
Uiree Jo

An adenomatoid tumor (AT) is a benign lesion, which is commonly located in the genital tract of both sexes. We present a case of a 66-yr-old woman with the unusual characteristics of an AT mimicking peritoneal carcinomatosis. The tumor was detected incidentally by ultrasound examination, and an ensuing imaging study raised suspicion of ovarian cancer with peritoneal carcinomatosis. From the pathologic diagnosis of frozen specimens, clear cell carcinoma was noted and the patient subsequently underwent cytoreductive surgery. An 8.5-cm-sized mass was observed on the uterine serosa, extending into the myometrium. In addition, multi-cystic nodular lesions were identified in the omentum, appendiceal and small bowel serosa, and the peritoneum. After histologic and extensive immunohistochemical examinations, the final diagnosis was AT. Recognition of the diverse presentations of AT is crucial for accurate diagnosis and appropriate treatment, as these tumors can involve multiple sites and mimic peritoneal carcinomatosis, potentially leading to a misdiagnosis of malignancy.

腺瘤(AT)是一种良性病变,常见于男女生殖道。我们介绍了一例 66 岁女性的病例,她的腺瘤具有模仿腹膜癌的不寻常特征。该肿瘤是在超声检查中偶然发现的,随后的影像学检查让人怀疑是卵巢癌伴腹膜癌转移。冰冻标本的病理诊断结果显示为透明细胞癌,患者随后接受了细胞切除手术。在子宫浆膜上发现了一个 8.5 厘米大小的肿块,并延伸至子宫肌层。此外,还在网膜、阑尾和小肠浆膜以及腹膜上发现了多囊结节病变。经过组织学和大量免疫组化检查,最终诊断为腹腔积液。认识到腹膜癌的多种表现形式对于准确诊断和适当治疗至关重要,因为这些肿瘤可累及多个部位并可模仿腹膜癌,从而可能导致恶性肿瘤的误诊。
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引用次数: 0
Molecular and Clinicopathologic Characterization of HER2-overexpressed Squamous Cell Carcinoma of the Cervix. 表达 HER2 的宫颈鳞状细胞癌的分子和临床病理学特征。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-31 DOI: 10.1097/PGP.0000000000001068
Rachelle P Mendoza, Madhurya Ramineni, Kristina Doytcheva, Elmer C Gabutan, Raavi Gupta, Cole Miller, Donghyuk Choi, Anusha Vemuri, Renee Briese, Lisa Brannon, Anum Shahid, Kristin Petras, Minhaz Ud Dean, Carrie Fitzpatrick, Jeremy Segal, Peng Wang, Ricardo R Lastra

HER2 amplification in cervical cancer has been associated with worse clinical prognosis and a potential favorable response to HER2 inhibitors. Immunohistochemistry for the HER2 receptor is a universally accepted surrogate test for HER2 amplification, but no standardized scoring system currently exists for cervical carcinomas. In this study, we investigated HER2 overexpression in cervical squamous cell carcinoma and correlated it with HER2 amplification using fluorescence in situ hybridization (FISH) and molecular methods. Seventy-two cases of human papillomavirus-associated cervical cancer were retrospectively reviewed, and at least 2 representative tumor sections were stained for HER2. HER2 scoring was performed using the 2018 American Society of Clinical Oncology/College of American Pathologist breast cancer criteria, and cases with equivocal (2+) to positive (3+) expression were analyzed for HER2 amplification using FISH and next-generation sequencing. The average patient age was 50 yrs (range: 27-85 yr), with most patients being African American (73.6%) and diagnosed at FIGO stage I (65.3%). Nineteen (26.4%) had equivocal HER2 expression and 4 (5.5%) showed positive expression. Three of the 4 cases with positive expression had enough tumors for FISH, and all 3 were amplified. Three cases with equivocal expression showed HER2 polysomy on FISH, and none showed HER2 amplification. Late clinical stage, high tumor grade, and regional lymph node metastasis were significantly correlated with HER2 overexpression and HER2 amplification. Next-generation sequencing of the 3 HER2-amplified tumors showed amplification of various genes, including CD274, JAK2, BIRC3, and ERBB2, and a PIK3CA missense mutation. In summary, HER2 immunohistochemistry is a reliable predictive marker of HER2 amplification in cervical cancer.

宫颈癌中的 HER2 扩增与较差的临床预后和对 HER2 抑制剂的潜在有利反应有关。HER2 受体免疫组化是公认的 HER2 扩增替代检测方法,但目前还没有针对宫颈癌的标准化评分系统。在这项研究中,我们使用荧光原位杂交(FISH)和分子方法研究了宫颈鳞状细胞癌中的 HER2 过表达,并将其与 HER2 扩增联系起来。对72例人乳头状瘤病毒相关宫颈癌病例进行了回顾性研究,并对至少2个具有代表性的肿瘤切片进行了HER2染色。采用2018年美国临床肿瘤学会/美国病理学家学会乳腺癌标准进行HER2评分,对表达不明确(2+)至阳性(3+)的病例采用FISH和下一代测序分析HER2扩增。患者平均年龄为 50 岁(范围:27-85 岁),大多数患者为非裔美国人(73.6%),确诊时处于 FIGO I 期(65.3%)。19例(26.4%)HER2表达不明确,4例(5.5%)呈阳性表达。4例阳性表达病例中,有3例的肿瘤足以进行FISH检查,且3例均有扩增。3例表达不明确的病例在FISH中显示出HER2多体,但没有一例显示出HER2扩增。临床分期晚、肿瘤分级高和区域淋巴结转移与HER2过表达和HER2扩增显著相关。对3个HER2扩增肿瘤进行的新一代测序显示,包括CD274、JAK2、BIRC3和ERBB2在内的多个基因发生了扩增,PIK3CA也发生了错义突变。总之,HER2 免疫组化是宫颈癌 HER2 扩增的可靠预测指标。
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引用次数: 0
High-grade Endometrial Carcinomas With Solid Basaloid Morphology and Geographic Necrosis Lacking Definitive Pilomatrix-like Features: Clinicopathologic Characteristics Including Aggressive Behavior and Novel Molecular Events. 高分化子宫内膜癌(High-grade Endometrial Carcinomas with Solid Basaloid Morphology and Geographic Necrosis Lacking Definitive Pilomatrix-like Features):包括侵袭行为和新分子事件在内的临床病理特征。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-31 DOI: 10.1097/PGP.0000000000001081
David K Carlson, Cheyenne Painter, Sarah E Gradecki, Kari L Ring, Eli S Williams, Anne M Mills

High-grade endometrioid carcinomas occasionally demonstrate solid basaloid morphology with geographic necrosis (SB-GN). This pattern is among the defining features of pilomatrix-like high-grade endometrioid carcinoma (PiMHEC), a recently proposed tumor type which is additionally characterized by the presence of shadow cells, abnormal beta-catenin/CTNNB1 mutations, strong CDX2 expression, and poor outcomes. Clinicopathologic overlap between PiMHEC and other high-grade endometrial cancers with SB-GN has not been established. We screened 300 endometrial carcinomas on tissue microarray for SB-GN histology and performed a detailed whole-section morphologic review, immunohistochemical analysis, and next-generation sequencing on all cases bearing this pattern. Four (1.3%) demonstrated SB-GN. All 3 with clinical follow-up had extremely aggressive behavior despite being MMR-deficient; in contrast, only 27% of other MMR-deficient high-grade carcinomas recurred. One SB-GN case met most of the previously outlined diagnostic criteria for PiMHEC including abnormal beta-catenin/CTNNB1 (p.S37P variant) and strong CDX2 expression; notably, however, shadow cells were absent. This case also demonstrated a KRAS p.A59T pathogenic variant. The other 3 cases also lacked shadow cells; the 2 with sequencing data bore no CTNNB1 abnormalities but showed likely oncogenic variants involving the pilomatrixoma-associated gene FGFR2. All 3 cases with molecular results also bore somatic Notch pathway (NOTCH1/NOTCH2/NOTCH3) variants. The single case treated with immunotherapy showed complete and sustained response with regression of bone metastases despite abnormal beta-catenin/CTNNB1, which has been associated with immunotherapeutic resistance. These data suggest that the SB-GN pattern may connote a poor prognosis even in the absence of overt pilomatrix-like differentiation, and that novel molecular events may have implications for the treatment of these tumors.

高分化子宫内膜样癌偶尔会出现实性基底细胞形态,并伴有地理坏死(SB-GN)。这种形态是柔膜样高级别子宫内膜样癌(PiMHEC)的特征之一,PiMHEC是最近提出的一种肿瘤类型,其特征还包括阴影细胞的存在、异常β-catenin/CTNNB1突变、CDX2的强表达和不良预后。PiMHEC 与其他伴有 SB-GN 的高级别子宫内膜癌之间的临床病理重叠尚未确定。我们通过组织芯片筛查了 300 例 SB-GN 组织学的子宫内膜癌,并对所有具有这种模式的病例进行了详细的全切片形态学检查、免疫组化分析和新一代测序。其中有 4 例(1.3%)表现为 SB-GN。尽管缺乏 MMR,但有临床随访的 3 例病例都具有极强的侵袭性;相比之下,其他缺乏 MMR 的高级别癌中只有 27% 复发。其中一个 SB-GN 病例符合之前概述的 PiMHEC 的大部分诊断标准,包括异常的 beta-catenin/CTNNB1(p.S37P 变异)和 CDX2 的强表达;但值得注意的是,该病例没有阴影细胞。该病例还显示出 KRAS p.A59T 致病变异。另外 3 个病例也没有阴影细胞;有测序数据的 2 个病例没有 CTNNB1 异常,但显示可能有涉及皮瘤相关基因 FGFR2 的致癌变异。所有3个有分子检测结果的病例都有体细胞Notch通路(NOTCH1/NOTCH2/NOTCH3)变异。尽管β-catenin/CTNNB1异常与免疫治疗耐药有关,但接受免疫治疗的单个病例显示出完全和持续的应答,骨转移灶消退。这些数据表明,SB-GN模式可能意味着预后不良,即使没有明显的皮瘤样分化,而且新的分子事件可能对这些肿瘤的治疗有影响。
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引用次数: 0
Lamin A and Emerin Protein Expression Remains Consistently Low and Nuclear Size is Unchanged in Normal Endometrium, Precancerous Lesions, and Endometrioid Carcinoma. 在正常子宫内膜、癌前病变和子宫内膜样癌中,Lamin A 和 Emerin 蛋白的表达量始终很低,核大小也没有变化。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-31 DOI: 10.1097/PGP.0000000000001080
Yoshimi Nishijima, Naoki Inoue, Akira Iwase, Hayato Ikota, Sayaka Kobayashi, Hideaki Yokoo, Masanao Saio

Nuclear laminar or inner nuclear membrane proteins, including lamin A, B1, and B2 and emerin, are involved in maintaining nuclear morphology. However, their expression patterns vary among tumors and remain incompletely understood. Endometrioid carcinoma (EC) exhibits mild nuclear atypia, although the underlying reasons have not been thoroughly explored. In this study, we quantitatively analyzed emerin and lamin A, B1, and B2 expression levels in normal endometrium (NE), precancerous lesions, and EC using computer-assisted image analysis to assess the proteins' roles in nuclear morphologic change during tumorigenesis. From NE to EC, nuclear size remained unchanged, and lamin A and emerin were consistently expressed at low levels, whereas lamin B1 and B2 expression gradually decreased. Given the association between lamin A and emerin as well as their roles in nuclear morphology, these results indicate that their consistent low expression may underlie the preservation of nuclear size and shape in EC relative to NE. Conversely, lamin B1 and B2 are implicated in tumor progression rather than nuclear morphology maintenance. As lamin A and emerin are expressed in many organs and tumors, the consistently low expression of these proteins from NE to EC highlights a notable feature of the endometrium and endometrial carcinogenesis.

核片层或核内膜蛋白,包括片层 A、B1 和 B2 以及应急蛋白,参与维持核形态。然而,它们在不同肿瘤中的表达模式各不相同,至今仍不完全清楚。子宫内膜样癌(EC)表现出轻度核不典型性,但其根本原因尚未得到深入探讨。在这项研究中,我们利用计算机辅助图像分析技术定量分析了正常子宫内膜(NE)、癌前病变和EC中emerin和层粘连蛋白A、B1和B2的表达水平,以评估这些蛋白在肿瘤发生过程中核形态变化中的作用。从NE到EC,核大小保持不变,层粘连蛋白A和emerin持续低水平表达,而层粘连蛋白B1和B2的表达则逐渐下降。鉴于片层A和胚乳素之间的联系以及它们在核形态中的作用,这些结果表明,它们持续低水平表达可能是相对于NE而言,EC中核大小和形状得以保留的原因。相反,片层蛋白 B1 和 B2 与肿瘤进展而非核形态维持有关。由于层粘连蛋白 A 和emerin 在许多器官和肿瘤中都有表达,因此这些蛋白从 NE 到 EC 的持续低表达突显了子宫内膜和子宫内膜癌变的一个显著特点。
{"title":"Lamin A and Emerin Protein Expression Remains Consistently Low and Nuclear Size is Unchanged in Normal Endometrium, Precancerous Lesions, and Endometrioid Carcinoma.","authors":"Yoshimi Nishijima, Naoki Inoue, Akira Iwase, Hayato Ikota, Sayaka Kobayashi, Hideaki Yokoo, Masanao Saio","doi":"10.1097/PGP.0000000000001080","DOIUrl":"10.1097/PGP.0000000000001080","url":null,"abstract":"<p><p>Nuclear laminar or inner nuclear membrane proteins, including lamin A, B1, and B2 and emerin, are involved in maintaining nuclear morphology. However, their expression patterns vary among tumors and remain incompletely understood. Endometrioid carcinoma (EC) exhibits mild nuclear atypia, although the underlying reasons have not been thoroughly explored. In this study, we quantitatively analyzed emerin and lamin A, B1, and B2 expression levels in normal endometrium (NE), precancerous lesions, and EC using computer-assisted image analysis to assess the proteins' roles in nuclear morphologic change during tumorigenesis. From NE to EC, nuclear size remained unchanged, and lamin A and emerin were consistently expressed at low levels, whereas lamin B1 and B2 expression gradually decreased. Given the association between lamin A and emerin as well as their roles in nuclear morphology, these results indicate that their consistent low expression may underlie the preservation of nuclear size and shape in EC relative to NE. Conversely, lamin B1 and B2 are implicated in tumor progression rather than nuclear morphology maintenance. As lamin A and emerin are expressed in many organs and tumors, the consistently low expression of these proteins from NE to EC highlights a notable feature of the endometrium and endometrial carcinogenesis.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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International Journal of Gynecological Pathology
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