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Clinicopathological study and molecular subtyping of muscle-invasive bladder cancer (MIBC) using dual immunohistochemical (IHC) markers.
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-24 DOI: 10.1186/s13000-025-01603-8
R Vaithegi, Kanthilatha Pai, Anuradha Calicut Kini Rao, Vidya Monappa, Swathi Prabhu, Nischitha Suvarna

Background: Muscle-invasive bladder carcinomas (MIBCs) exhibit significant heterogeneity, with diverse histopathological features associated with varied prognosis and therapeutic response. Although genomic profiling studies have identified several molecular subtypes of MIBC, two basic molecular subtypes are identified - luminal and basal, differing in biological behaviour and response to treatment. As molecular subtyping is complex, surrogate immunohistochemical (IHC) markers have been used to determine the molecular subtypes with good correlation to genomic profiling.

Methods: We analysed the clinicopathological features of 66 cases of MIBCs received over a 5-year study period. IHC expression was determined using GATA3 and CK5/6 to classify MIBC into luminal, basal and double-negative subtypes. The association between clinicopathologic variables and molecular subtypes were analysed using Chi-square test.

Results: The mean age at diagnosis of MIBC was 65.91 years with a male predominance. Based on IHC expression of GATA3 and CK5/6, MIBCs were classified into luminal, basal and double negative subtypes in 62.1%, 30.3% and 7.6% respectively. The luminal subtype occurred at an older age and showed predominantly conventional urothelial carcinoma with papillary morphology. Basal subtype occurred at earlier age, showed greater association with smoking and was more commonly associated with urothelial carcinoma with non -papillary morphology and exhibiting divergent differentiation as well as pure squamous cell carcinoma on histopathological examination. The double-negative subtype was found exclusively in males and exhibited a non-papillary morphology. Notably, all diagnosed neuroendocrine carcinomas were classified as double-negative type. While there was no statistically significant difference in tumour stage in cystectomy specimens between the molecular subtypes, lympho-vascular invasion and lymph node metastasis was more commonly associated with the basal type (p < 0.05) There was no significant difference in recurrence rates, metastasis and death between luminal and basal subtypes.

Conclusion: A simple two-antibody panel using GATA3 and CK5/6 could help in classifying MIBC into basic molecular subtypes of MIBC with distinctive histopathological features that can provide insights into the corresponding molecular subtype. Greater association of lymphovascular invasion and lymph nodal involvement in cystectomy specimens in basal type and distant metastasis in the double-negative subtype suggests a more aggressive clinical behaviour of these, necessitating more intensive treatment.

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引用次数: 0
Immunohistochemical expression of parathyroid hormone-related protein and ezrin in invasive breast carcinoma of no special type: a retrospective analysis. 非特殊类型浸润性乳腺癌中甲状旁腺激素相关蛋白和ezrin的免疫组化表达:回顾性分析。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-18 DOI: 10.1186/s13000-025-01598-2
Menna Allah Gamil Ali Shalaby, Marwa Mohammed Dawoud, Marwa Salah Gadallah, Asmaa Gaber Abdou

Background: Globally, breast cancer ranks among the most common malignancies and has a high mortality rate. Invasive breast carcinoma of no special type (IBC-NST) presents a heterogeneous group with variable prognosis. Identifying reliable biomarkers is crucial for improving treatment strategies and predicting outcomes. This study investigates the immunohistochemical expression of parathyroid hormone-related protein (PTHrP) and ezrin in IBC-NST and their correlation with clinicopathological features and overall survival.

Methods: This retrospective study analyzed 160 paraffin-embedded tissue samples, including 123 IBC-NST and 37 normal breast tissues, collected from patients treated at Menoufia University Hospital during the period from January 2018 to January 2022. Immunohistochemical staining for PTHrP and ezrin was performed, and expression levels were quantified using the H score.

Results: PTHrP expression was significantly higher in IBC-NST than in adjacent DCIS and normal tissues (p < 0.001). High PTHrP percent of expression was associated with metastasis (p = 0.009), bone metastasis (p = 0.012), and lymphovascular invasion (p = 0.037). Ezrin expression was also significantly elevated in IBC-NST, with higher H score values correlating with high tumor grade (p = 0.002), high N stage (p = 0.045), advanced AJCC stage grouping (p = 0.0043) and metastasis (p = 0.001). A significant positive correlation was observed between PTHrP and ezrin expression (rs = 0.341, p < 0.001). Kaplan-Meier analysis showed that high ezrin expression, in terms of intensity (p = 0.007) and H score (p = 0.002), was linked to poorer survival.

Conclusion: The study highlights the significant roles of PTHrP and ezrin in breast cancer progression. Elevated levels of these proteins are associated with more aggressive disease, suggesting their capability as prognostic indicators and treatment targets in breast cancer. Additional studies are required to investigate their interaction and collective influence on breast cancer metastasis and treatment.

背景:在全球范围内,乳腺癌是最常见的恶性肿瘤之一,死亡率很高。无特殊类型浸润性乳腺癌(IBC-NST)呈现异质性,预后各异。确定可靠的生物标志物对于改善治疗策略和预测结果至关重要。本研究探讨了IBC-NST中甲状旁腺激素相关蛋白(PTHrP)和ezrin的免疫组化表达及其与临床病理特征和总生存率的关系。方法:本回顾性研究分析了2018年1月至2022年1月在Menoufia大学医院治疗的患者的160例石蜡包埋组织样本,其中123例为IBC-NST, 37例为正常乳腺组织。对PTHrP和ezrin进行免疫组化染色,并用H评分定量表达水平。结果:PTHrP在IBC-NST中的表达明显高于邻近DCIS和正常组织(p结论:本研究强调了PTHrP和ezrin在乳腺癌进展中的重要作用。这些蛋白水平的升高与更具侵袭性的疾病有关,这表明它们可以作为乳腺癌的预后指标和治疗靶点。需要进一步的研究来调查它们对乳腺癌转移和治疗的相互作用和集体影响。
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引用次数: 0
TFE3-rearranged perivascular epithelioid cell tumors of the head and neck with rare fusion partners: clues to the differential diagnosis between benign and malignant tumors.
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-15 DOI: 10.1186/s13000-025-01602-9
Yuka Takahashi, Akihiko Yoshida, Seiichi Yoshimoto, Shigenobu Suzuki, Satsuki Kishikawa, Ayaka Mitsui, Eijitsu Ryo, Yuki Kojima, Kan Yonemori, Yasushi Yatabe, Taisuke Mori

Background: Perivascular epithelioid cell tumors (PEComas) rarely appear in the head and neck region. This case report describes two transcription factor E3 (TFE3)-rearranged PEComa cases, consisting of one in the orbit and one in the nasal cavity.

Case presentation: Both cases demonstrated sheet-like or focal nested architecture and comprised epithelioid cells with abundant clear to eosinophilic cytoplasm and vascular stroma. The first case exhibited partial pleomorphism, a small necrosis area, and slightly increased mitosis and was classified as malignant. The second case demonstrated mild atypia and no mitosis or necrosis and was categorized as benign. The nasal tumor was initially considered a TFE3-rearranged renal cell carcinoma metastasis. However, a subsequent renal tumor biopsy revealed angiomyolipoma. The RNA sequence revealed ZC3H4::TFE3 and PRCC::TFE3 fusions in the first and second cases, respectively.

Conclusion: The fusion partner gene ZC3H4 is uncommon, and this is the third reported PEComa case. The fusion partner gene PRCC is often reported in TFE3-rearranged renal cell carcinoma, and this PEComa case is the second reported in the head and neck region. The initially reported cases with the fusion partner genes ZC3H4 and PRCC were categorized as malignant. These cases were discussed with a literature review.

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引用次数: 0
Synchronous clonally related anaplastic large cell lymphoma and malignant histiocytosis. 同步克隆相关间变性大细胞淋巴瘤和恶性组织细胞增多症。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-14 DOI: 10.1186/s13000-025-01597-3
Mirvate Harb, Tom Abrassart, Laurent Dewispeleare, Pierre Sidon, Natacha Dirckx, Anne-Laure Trepant, Julie Castiaux, Pierre Heimann, Jean-Francois Emile, Hussein Farhat

Background: Synchronous malignant histiocytoses are rare conditions that occur concurrently with another hematologic neoplasm. Most reported cases are associated with B-cell lymphoproliferative disorders, while associations with T-cell hemopathies are less common. These two diseases may share mutations and/or cytogenetic anomalies, which can lead to malignant proliferations. In such cases, the term "secondary malignant histiocytosis" can be applied.

Case description: A 26-year-old patient was diagnosed with anaplastic lymphoma kinase negative anaplastic large cell lymphoma [ALK-ALCL] associated with synchronous malignant histiocytosis. Neoplastic cells were distinguished by the exclusivity of the rearrangement of TCR genes within the lymphoma cells, whereas mutations in the KRAS and TP53 genes affected mono-histiocytic cells. However, these two cells populations shared common chromosomal abnormalities. First line treatment protocol included Brentuximab vedotin, cyclophosphamide, doxorubicin, and methylprednisolone. Despite a partial clinical and biological response after cycle 1 of treatment, the patient was refractory at the end of cycle 2. Patient died in the intensive care unit from a multiple-organ failure related to lymphohistiocytic hemophagocytosis.

Conclusion: This case represents the first documented instance of synchronous malignant histiocytosis associated with anaplastic large cell lymphoma. Notably, the uniqueness of this case lies in the absence of TCR rearrangement in the histiocytic cells, despite the presence of shared chromosomal abnormalities with the lymphomatous cells indicating a common origin for both neoplastic proliferations. Considering the rarity of such occurrences, the use of histiocytosis targeted therapy alongside conventional lymphoma treatment warrants consideration in such a context.

背景:与其他血液肿瘤同时发生的恶性组织细胞增多症是罕见的。大多数报告的病例与b细胞淋巴增生性疾病有关,而与t细胞血液病的关联则不太常见。这两种疾病可能有共同的突变和/或细胞遗传学异常,这可能导致恶性增殖。在这种情况下,可以使用术语“继发性恶性组织细胞增多症”。病例描述:一位26岁的患者被诊断为间变性淋巴瘤激酶阴性间变性大细胞淋巴瘤[ALK-ALCL]并伴有同步恶性组织细胞增多症。肿瘤细胞的特点是淋巴瘤细胞中TCR基因重排的排他性,而KRAS和TP53基因的突变影响单组织细胞。然而,这两个细胞群有共同的染色体异常。一线治疗方案包括布伦妥昔单抗维多汀、环磷酰胺、阿霉素和甲基强的松龙。尽管在第1周期治疗后出现部分临床和生物学反应,但患者在第2周期结束时仍难治性。患者死于与淋巴组织细胞噬血细胞症相关的多器官衰竭。结论:本病例是第一例伴有间变性大细胞淋巴瘤的同步恶性组织细胞增多症。值得注意的是,该病例的独特之处在于组织细胞中没有TCR重排,尽管与淋巴瘤细胞存在共同的染色体异常,表明两种肿瘤增生有共同的起源。考虑到这种情况的罕见性,在这种情况下,组织细胞增多症靶向治疗与传统淋巴瘤治疗一起使用值得考虑。
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引用次数: 0
Exploring the heterogeneity of HER2 gene status and expression in non-positive breast cancer patients: insights from immunohistochemistry and fluorescence in situ hybridization. 探讨非阳性乳腺癌患者中HER2基因状态和表达的异质性:免疫组织化学和荧光原位杂交的见解
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-10 DOI: 10.1186/s13000-024-01594-y
Jingmin Zhong, Beibei Gao, Qingjie Wang, Jun He, Danjv Luo, Chen Zhang, Jun Fan, Xiu Nie

Breast cancer became the most prevalent malignancy among women, and HER2 expression status is critical for treatment decisions. With the emergence of ADC drugs, HER2 low-expressing patients who previously did not respond well to traditional anti-HER2 therapies may now benefit. In this study, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were applied to assess HER2 expression in 349 patients with HER2-non-positive breast cancer. Our analysis revealed that HER2-low tumors exhibited fewer grade III tumors (39.74% and 55.65%, respectively, P = 0.005) and higher positivity for estrogen receptor (ER, 88.89% vs. 61.74%, P < 0.001) and progesterone receptor (PR, 84.62% vs. 57.39%, P < 0.001) compared to HER2-ZERO tumors. Of the 349 cases, IHC was ultimately evaluated in 327, the antibodies demonstrated only 64.22% (95% CI: 58.76-69.42%) agreement between clone 4B5 and clone EP3. Pathologist 1, who had more extensive working experience, demonstrated higher consistency (94.19%) with the gold standard when using clone EP3, compared to Pathologist 2 (74.31%). FISH analysis revealed significant differences in HER2/CEP17 ratio and average HER2 copy numbers between HER2-ZERO and HER2-low tumors, but no clear cut-off value could be identified. Notably, HER2/CEP17 ratio mostly between 1 and 2, with HER2-ZERO tumors primarily ≤ 1.4, and average HER2 copy numbers were mostly ≥ 2 and < 4, with HER2-ZERO tumors primarily ≤ 2.5. Despite distinct clinicopathological features, FISH remains inadequate for distinguishing HER2-low from HER2-ZERO expression. Further studies are needed to improve HER2 assessment in this challenging subset of patients.

乳腺癌已成为女性中最常见的恶性肿瘤,HER2表达状况对治疗决策至关重要。随着ADC药物的出现,以前对传统抗HER2治疗反应不佳的HER2低表达患者现在可能受益。在这项研究中,应用免疫组织化学(IHC)和荧光原位杂交(FISH)技术评估了349例HER2非阳性乳腺癌患者的HER2表达。我们的分析显示HER2-low肿瘤中III级肿瘤较少(分别为39.74%和55.65%,P = 0.005),雌激素受体阳性较高(ER, 88.89%比61.74%,P = 0.005)
{"title":"Exploring the heterogeneity of HER2 gene status and expression in non-positive breast cancer patients: insights from immunohistochemistry and fluorescence in situ hybridization.","authors":"Jingmin Zhong, Beibei Gao, Qingjie Wang, Jun He, Danjv Luo, Chen Zhang, Jun Fan, Xiu Nie","doi":"10.1186/s13000-024-01594-y","DOIUrl":"10.1186/s13000-024-01594-y","url":null,"abstract":"<p><p>Breast cancer became the most prevalent malignancy among women, and HER2 expression status is critical for treatment decisions. With the emergence of ADC drugs, HER2 low-expressing patients who previously did not respond well to traditional anti-HER2 therapies may now benefit. In this study, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were applied to assess HER2 expression in 349 patients with HER2-non-positive breast cancer. Our analysis revealed that HER2-low tumors exhibited fewer grade III tumors (39.74% and 55.65%, respectively, P = 0.005) and higher positivity for estrogen receptor (ER, 88.89% vs. 61.74%, P < 0.001) and progesterone receptor (PR, 84.62% vs. 57.39%, P < 0.001) compared to HER2-ZERO tumors. Of the 349 cases, IHC was ultimately evaluated in 327, the antibodies demonstrated only 64.22% (95% CI: 58.76-69.42%) agreement between clone 4B5 and clone EP3. Pathologist 1, who had more extensive working experience, demonstrated higher consistency (94.19%) with the gold standard when using clone EP3, compared to Pathologist 2 (74.31%). FISH analysis revealed significant differences in HER2/CEP17 ratio and average HER2 copy numbers between HER2-ZERO and HER2-low tumors, but no clear cut-off value could be identified. Notably, HER2/CEP17 ratio mostly between 1 and 2, with HER2-ZERO tumors primarily ≤ 1.4, and average HER2 copy numbers were mostly ≥ 2 and < 4, with HER2-ZERO tumors primarily ≤ 2.5. Despite distinct clinicopathological features, FISH remains inadequate for distinguishing HER2-low from HER2-ZERO expression. Further studies are needed to improve HER2 assessment in this challenging subset of patients.</p>","PeriodicalId":11237,"journal":{"name":"Diagnostic Pathology","volume":"20 1","pages":"4"},"PeriodicalIF":2.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fasciolopsis buski infection of the biliary tract: a case report. 胆道布氏片形虫感染1例。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-10 DOI: 10.1186/s13000-025-01600-x
Shuai Luo, Xiaoxue Tian, Ting Xu, Jinjing Wang

Background: Fasciolopsis buski is a large fluke that parasitises the human small intestine, with its infection in the biliary tract being even rarer. Given its relatively rare occurrence in recent years, the clinical diagnosis of F. buski infections can pose certain challenges.

Case demonstration: A 59-year-old male patient with a history of consuming raw pig blood was admitted with recurrent upper abdominal pain for over 10 years. Hepatobiliary and pancreatic magnetic resonance cholangiopancreatography showed stenosis of the lower end of the common bile duct, dilatation of the intrahepatic and extrahepatic bile ducts above, and tortuous strips in the common bile duct, indicating parasitic infection. Histopathological examination further confirmed a diagnosis of parasitic infection with F. buski in the biliary tract. The patient was treated with praziquantel after surgery and did not exhibit recurrence during 6 months of follow-up.

Conclusions: Biliary tract infection with F. buski is a rare parasitic disease. This case report discusses an extremely rare case of F. buski infection of the biliary tract caused by consuming raw pig blood. The clinical features, common diagnostic methods, imaging and pathological features, differential diagnosis, treatment, and prognosis of this disease were reviewed to facilitate an improved understanding of this rare condition.

背景:buski片形虫是一种寄生于人类小肠的大型吸虫,其在胆道的感染更为罕见。鉴于近年来其相对罕见的发生,临床诊断的布氏乳杆菌感染可以提出一定的挑战。病例论证:59岁男性患者,有食生猪血史,因复发性上腹痛10年以上入院。肝胆胰核磁共振胆管造影示胆总管下端狭窄,上方肝内、肝外胆管扩张,胆总管呈扭曲条状,提示寄生虫感染。组织病理学检查进一步证实了胆道寄生虫感染的诊断。患者术后给予吡喹酮治疗,随访6个月未出现复发。结论:胆道感染是一种罕见的寄生虫病。本病例报告讨论了一个极其罕见的病例布氏弧菌感染胆道引起食用生猪血。本文对本病的临床特点、常用诊断方法、影像学及病理特征、鉴别诊断、治疗及预后进行综述,以提高对本病的认识。
{"title":"Fasciolopsis buski infection of the biliary tract: a case report.","authors":"Shuai Luo, Xiaoxue Tian, Ting Xu, Jinjing Wang","doi":"10.1186/s13000-025-01600-x","DOIUrl":"10.1186/s13000-025-01600-x","url":null,"abstract":"<p><strong>Background: </strong>Fasciolopsis buski is a large fluke that parasitises the human small intestine, with its infection in the biliary tract being even rarer. Given its relatively rare occurrence in recent years, the clinical diagnosis of F. buski infections can pose certain challenges.</p><p><strong>Case demonstration: </strong>A 59-year-old male patient with a history of consuming raw pig blood was admitted with recurrent upper abdominal pain for over 10 years. Hepatobiliary and pancreatic magnetic resonance cholangiopancreatography showed stenosis of the lower end of the common bile duct, dilatation of the intrahepatic and extrahepatic bile ducts above, and tortuous strips in the common bile duct, indicating parasitic infection. Histopathological examination further confirmed a diagnosis of parasitic infection with F. buski in the biliary tract. The patient was treated with praziquantel after surgery and did not exhibit recurrence during 6 months of follow-up.</p><p><strong>Conclusions: </strong>Biliary tract infection with F. buski is a rare parasitic disease. This case report discusses an extremely rare case of F. buski infection of the biliary tract caused by consuming raw pig blood. The clinical features, common diagnostic methods, imaging and pathological features, differential diagnosis, treatment, and prognosis of this disease were reviewed to facilitate an improved understanding of this rare condition.</p>","PeriodicalId":11237,"journal":{"name":"Diagnostic Pathology","volume":"20 1","pages":"5"},"PeriodicalIF":2.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Complex immunohistochemical and molecular study on 5 cases of ovarian juvenile granulosa cell tumors reveals a consistent alteration in the PI3K/AKT/mTOR signaling pathway. 5例卵巢幼年颗粒细胞瘤的复杂免疫组织化学和分子研究显示PI3K/AKT/mTOR信号通路的一致改变。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-08 DOI: 10.1186/s13000-025-01599-1
Adam Šafanda, Nikola Hájková, Michaela Kendall Bártů, Marián Švajdler, Radoslav Matěj, Jitka Hausnerová, Tomáš Zima, Pavel Dundr, Kristýna Němejcová

Background: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT.

Methods: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated. Moreover, DNA next-generation sequencing (NGS) and PTEN methylation analysis was performed.

Result: We found the expression of calretinin, inhibin A, SF1, FOXL2, CD99, CKAE1/3, ER, PR, AR in all cases. WT1 was expressed in one case. Conversely, the expression of p16, OCT3/4, SALL4, GATA3, Napsin A, SATB2, MUC4, TTF1, and CAIX was completely negative. All tumors showed the wild-type pattern of p53 expression. Regarding predictive markers, all tumors were HER2 negative and did not express PD-L1. Mismatch repair proteins (MMR) showed no loss or restriction of expression, similarly to ARID1A, DPC4, BRG1, and INI1. The molecular analysis revealed AKT1 internal tandem duplication in two tumors. Two other cases exhibited mutations in TERT and EP400 and both developed recurrence. All AKT1-wild type tumors exhibited immunohistochemical loss of PTEN expression. However, no mutations, deletions (as assessed by CNV analysis), or promoter hypermethylation in the PTEN gene were detected.

Conclusion: The results of our study further support the hypothesis that the pathogenesis of JGCT may be driven by activation of the PIK3/AKT/mTOR pathway. These findings could potentially have future therapeutic implications, as treatment strategies targeting the PTEN/mTOR pathways are currently under investigation.

背景:卵巢少年颗粒细胞瘤(JGCT)是一种罕见的肿瘤,具有独特的临床病理和激素特征,主要影响年轻妇女和儿童。我们对5例JGCT进行了复杂的临床病理、免疫组织化学和分子分析。方法:采用32种标记物进行免疫组化检查,包括以前未研究过的标记物。此外,还进行了DNA下一代测序(NGS)和PTEN甲基化分析。结果:calretinin、inhibin A、SF1、FOXL2、CD99、CKAE1/3、ER、PR、AR在所有病例中均有表达。WT1在1例中表达。相反,p16、OCT3/4、SALL4、GATA3、Napsin A、SATB2、MUC4、TTF1、CAIX表达完全阴性。所有肿瘤均显示p53野生型表达。关于预测标志物,所有肿瘤均为HER2阴性,不表达PD-L1。与ARID1A、DPC4、BRG1和INI1类似,错配修复蛋白(MMR)的表达没有丢失或受限。分子分析显示两个肿瘤中存在AKT1内部串联重复。另外2例出现TERT和EP400突变,均出现复发。所有akt1野生型肿瘤均表现PTEN的免疫组化表达缺失。然而,在PTEN基因中没有检测到突变、缺失(通过CNV分析评估)或启动子超甲基化。结论:本研究结果进一步支持了JGCT发病机制可能由PIK3/AKT/mTOR通路激活驱动的假说。这些发现可能对未来的治疗有潜在的影响,因为针对PTEN/mTOR通路的治疗策略目前正在研究中。
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引用次数: 0
The immunohistochemical combination of low SGLT2 expression and high PRDX4 expression independently predicts shortened survival in patients undergoing surgical resection for hepatoblastoma. 低SGLT2表达和高PRDX4表达的免疫组化联合独立预测肝母细胞瘤手术切除患者的生存期缩短。
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-08 DOI: 10.1186/s13000-025-01596-4
Yao Liu, Jia Han, Akihiro Shioya, Yang-Xian Zhang, Vu Anh Dung, Takeru Oyama, Xin Guo, Qian Yang, Tohru Ito, Sohsuke Yamada

Background: Hepatoblastoma (HB) is the most common malignant solid tumor of the liver in children and is a fatal disease with a poor prognosis. Therefore, indicators that can be used for the early prediction of the HB prognosis are necessary. Sodium glucose cotransporter 2 (SGLT2) is a glucose transporter protein present in the proximal renal tubules. Studies have shown that SGLT2 is associated with the occurrence of tumors and is upregulated in various tumors. Peroxiredoxin 4 (PRDX4) is an antioxidant enzyme with a secretory function and is located in the cytoplasmic endoplasmic reticulum. Recent reports have suggested that it is closely related to the development and prognosis of various cancers. To some degree, this is highly suggestive of the interplay between SGLT2 and PRDX4.

Methods: In the present study, clinical data and post-surgical paraffin-embedded specimens from 75 HB patients were collected, and hematoxylin and eosin and immunohistochemical staining of SGLT2 and PRDX4 were used to analyze their expression and correlation with the clinicopathological features and prognosis.

Results: We found that low SGLT2 and high PRDX4 expression predicted a significantly shorter survival and worse clinical condition in HB patients. Furthermore, when low SGLT2 expression was combined with high PRDX4 expression, the event-free survival and overall survival were significantly reduced. Univariate and multivariate Cox proportional hazards analyses showed that low SGLT2 and high PRDX4 expression in HB were independent prognostic factors for the survival after surgical resection.

Conclusion: The immunohistochemical combination of low SGLT2 and high PRDX4 expression can independently predict a poor prognosis in HB patients.

背景:肝母细胞瘤(HB)是儿童肝脏最常见的恶性实体瘤,是一种预后不良的致命疾病。因此,能够用于早期预测HB预后的指标是必要的。钠葡萄糖共转运蛋白2 (SGLT2)是存在于近端肾小管中的葡萄糖转运蛋白。研究表明,SGLT2与肿瘤的发生有关,在多种肿瘤中表达上调。过氧化氧还蛋白4 (PRDX4)是一种具有分泌功能的抗氧化酶,位于细胞质内质网中。最近的报道表明,它与各种癌症的发展和预后密切相关。在某种程度上,这高度暗示了SGLT2和PRDX4之间的相互作用。方法:本研究收集75例HB患者的临床资料及术后石蜡包埋标本,采用苏木精、伊红及免疫组化染色分析SGLT2、PRDX4的表达及其与临床病理特征及预后的相关性。结果:我们发现,低SGLT2和高PRDX4表达预示着HB患者的生存期明显缩短,临床状况更差。此外,当SGLT2低表达与PRDX4高表达结合时,无事件生存期和总生存期均显著降低。单因素和多因素Cox比例风险分析显示,HB中SGLT2低表达和PRDX4高表达是手术切除后生存的独立预后因素。结论:低SGLT2和高PRDX4表达的免疫组化联合可独立预测HB患者的不良预后。
{"title":"The immunohistochemical combination of low SGLT2 expression and high PRDX4 expression independently predicts shortened survival in patients undergoing surgical resection for hepatoblastoma.","authors":"Yao Liu, Jia Han, Akihiro Shioya, Yang-Xian Zhang, Vu Anh Dung, Takeru Oyama, Xin Guo, Qian Yang, Tohru Ito, Sohsuke Yamada","doi":"10.1186/s13000-025-01596-4","DOIUrl":"https://doi.org/10.1186/s13000-025-01596-4","url":null,"abstract":"<p><strong>Background: </strong>Hepatoblastoma (HB) is the most common malignant solid tumor of the liver in children and is a fatal disease with a poor prognosis. Therefore, indicators that can be used for the early prediction of the HB prognosis are necessary. Sodium glucose cotransporter 2 (SGLT2) is a glucose transporter protein present in the proximal renal tubules. Studies have shown that SGLT2 is associated with the occurrence of tumors and is upregulated in various tumors. Peroxiredoxin 4 (PRDX4) is an antioxidant enzyme with a secretory function and is located in the cytoplasmic endoplasmic reticulum. Recent reports have suggested that it is closely related to the development and prognosis of various cancers. To some degree, this is highly suggestive of the interplay between SGLT2 and PRDX4.</p><p><strong>Methods: </strong>In the present study, clinical data and post-surgical paraffin-embedded specimens from 75 HB patients were collected, and hematoxylin and eosin and immunohistochemical staining of SGLT2 and PRDX4 were used to analyze their expression and correlation with the clinicopathological features and prognosis.</p><p><strong>Results: </strong>We found that low SGLT2 and high PRDX4 expression predicted a significantly shorter survival and worse clinical condition in HB patients. Furthermore, when low SGLT2 expression was combined with high PRDX4 expression, the event-free survival and overall survival were significantly reduced. Univariate and multivariate Cox proportional hazards analyses showed that low SGLT2 and high PRDX4 expression in HB were independent prognostic factors for the survival after surgical resection.</p><p><strong>Conclusion: </strong>The immunohistochemical combination of low SGLT2 and high PRDX4 expression can independently predict a poor prognosis in HB patients.</p>","PeriodicalId":11237,"journal":{"name":"Diagnostic Pathology","volume":"20 1","pages":"2"},"PeriodicalIF":2.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gene expression and immunohistochemistry analysis of ADAMTS-1 and its substrates in odontogenic keratocyst.
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2025-01-07 DOI: 10.1186/s13000-024-01576-0
Osvaldo Rodrigues de Souza Neto, Antonia Taiane Lopes de Moraes, Hellen Thais Fuzii, Antonio Guilherme Maneschy Faria, Vanessa Morais Freitas, Maria Sueli da Silva Kataoka, Sérgio de Melo Alves, João de Jesus Viana Pinheiro

Background: Considering the significant participation of the microenvironment in the local aggressiveness of odontogenic keratocysts, this study aims to evaluate the expression of ADAMTS-1 and its substrates, versican, aggrecan and brevican in this locally invasive odontogenic cyst.

Methods: Immunohistochemistry and polymerase chain reaction (PCR) were conducted on 30 cases of odontogenic keratocysts (OKCs) and 20 dental follicles (DFs).

Results: The immunohistochemical expression of these proteins was predominantly cytoplasmic and granular across all samples. In epithelial tissue, the immunoexpression of aggrecan and versican was higher in OKC (p < 0.05) compared to DF. Comparing the expression of proteins between the OKC epithelium and the cystic capsule, it was observed that all molecules were more expressed in the epithelium (p < 0.001). RT-PCR confirmed the expression of ADAMTS-1 and proteoglycans in all samples.

Conclusion: ADAMTS-1, aggrecan, brevican, and versican were expressed in all samples with a granular and cytoplasmic pattern. RT-PCR confirmed their presence in both OKC and DF, but only aggrecan and versican exhibited significantly higher levels in OKC (p < 0.05). Protein expression was notably greater in the epithelial component of OKC. These findings underscore the potential role of these proteins in the biological behavior of OKC.

{"title":"Gene expression and immunohistochemistry analysis of ADAMTS-1 and its substrates in odontogenic keratocyst.","authors":"Osvaldo Rodrigues de Souza Neto, Antonia Taiane Lopes de Moraes, Hellen Thais Fuzii, Antonio Guilherme Maneschy Faria, Vanessa Morais Freitas, Maria Sueli da Silva Kataoka, Sérgio de Melo Alves, João de Jesus Viana Pinheiro","doi":"10.1186/s13000-024-01576-0","DOIUrl":"https://doi.org/10.1186/s13000-024-01576-0","url":null,"abstract":"<p><strong>Background: </strong>Considering the significant participation of the microenvironment in the local aggressiveness of odontogenic keratocysts, this study aims to evaluate the expression of ADAMTS-1 and its substrates, versican, aggrecan and brevican in this locally invasive odontogenic cyst.</p><p><strong>Methods: </strong>Immunohistochemistry and polymerase chain reaction (PCR) were conducted on 30 cases of odontogenic keratocysts (OKCs) and 20 dental follicles (DFs).</p><p><strong>Results: </strong>The immunohistochemical expression of these proteins was predominantly cytoplasmic and granular across all samples. In epithelial tissue, the immunoexpression of aggrecan and versican was higher in OKC (p < 0.05) compared to DF. Comparing the expression of proteins between the OKC epithelium and the cystic capsule, it was observed that all molecules were more expressed in the epithelium (p < 0.001). RT-PCR confirmed the expression of ADAMTS-1 and proteoglycans in all samples.</p><p><strong>Conclusion: </strong>ADAMTS-1, aggrecan, brevican, and versican were expressed in all samples with a granular and cytoplasmic pattern. RT-PCR confirmed their presence in both OKC and DF, but only aggrecan and versican exhibited significantly higher levels in OKC (p < 0.05). Protein expression was notably greater in the epithelial component of OKC. These findings underscore the potential role of these proteins in the biological behavior of OKC.</p>","PeriodicalId":11237,"journal":{"name":"Diagnostic Pathology","volume":"20 1","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
(1, 3)-beta-D-Glucan in bronchoalveolar lavage fluid: a useful biomarker in diagnosis of invasive pulmonary infection caused by Hormographiella aspergillata? 支气管肺泡灌洗液中的(1,3)- β - d -葡聚糖:诊断曲霉乳杆菌引起的侵袭性肺部感染的有用生物标志物?
IF 2.4 3区 医学 Q2 PATHOLOGY Pub Date : 2024-12-28 DOI: 10.1186/s13000-024-01589-9
Haiyan Ye, Jinhui He, Jing Huang, Patrick Chu, Junru Liu, Rosana Wing-Shan Poon, Fanfan Xing, Simon Kam-Fai Lo, Ricky Wing-Tong Lau, Jasper Fuk-Woo Chan, Susanna Kar-Pui Lau, Kelvin Hei-Yeung Chiu

Hormographiella aspergillata is a rare hyaline mold causing invasive fungal infection in humans, until the frequent use of antifungal prophylaxis in immunocompromised hosts. Due to the high mortality of H. aspergillata infection, early recognition and treatment are crucial. Previous case reports suggested that serum (1,3)-beta-D-Glucan (BG) is one of the diagnostic aids for H. aspergillata infection. Here we report for the first time a case of pulmonary H. aspergillata infection with a negative serum BG but positive bronchoalveolar lavage fluid (BAL) BG. This may suggest that BAL BG is a useful and additional microbiological marker for prompt identification of this fatal invasive fungal infection (IFI). But it should be interpreted together with the clinical presentation, imaging, and other laboratory results.

曲霉红曲霉是一种罕见的透明霉菌引起侵袭性真菌感染的人,直到经常使用抗真菌预防免疫功能低下的宿主。由于曲霉菌感染的高死亡率,早期识别和治疗至关重要。以往的病例报告表明,血清(1,3)- β - d -葡聚糖(BG)是曲霉感染的诊断辅助工具之一。在这里,我们报告了第一例肺部曲霉菌感染阴性血清BG但阳性支气管肺泡灌洗液(BAL) BG。这可能表明BAL BG是一种有用的微生物标志物,可以快速识别这种致命的侵袭性真菌感染(IFI)。但它应与临床表现、影像学和其他实验室结果一起解释。
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Diagnostic Pathology
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