Chae Young Shin, Bengul Gokbayrak, Valerie L Tao, Noorah Almadani, Eunice S Li, Rebecca Ho, Felix Kf Kommoss, Jutta Huvila, Derek Chiu, Samuel Leung, Basile Tessier-Cloutier, David G Huntsman, C Blake Gilks, Jessica N McAlpine, Lynn Hoang, Yemin Wang
Aims: Classification and risk stratification of endometrial carcinoma (EC) has transitioned from histopathological features to molecular classification, e.g. the ProMisE classifier, identifying four prognostic subtypes: POLE mutant (POLEmut) with almost no recurrence or disease-specific death events, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP), with intermediate outcome and p53 abnormal (p53abn) with poor outcomes. However, the applicability of molecular classification is unclear in rare but aggressive histotypes of EC, e.g. de-differentiated and undifferentiated endometrial cancers (DD/UDEC). Here, we aim to assembled a cohort of DD/UDEC from a single institution and analysed the prognostic significance of ProMisE molecular subtypes and the expression of SWItch/sucrose non-fermentable (SWI/SNF) chromatin remodelling complex members, previously implicated in the pathogenesis of DD/UDEC.
Methods and results: We accrued 88 DD/UDEC cases, assessed POLE status by Sanger sequencing and performed immunohistochemistry for p53, mismatch repair and SWI/SNF proteins on the tissue microarrays assembled. Assignment of molecular subtypes was possible in 80 tumours; POLE sequencing failed in the remaining eight cases. There were 12 (15%) POLEmut, 44 (55%) MMRd, 14 (17.5%) p53abn and 10 (12.5%) NSMP DD/UDEC. POLEmut DD/UDECs had excellent outcomes, but the other three molecular subtypes all had poor outcomes, with no significant differences among them. The loss of one or more SWI/SNF proteins [AT-rich interactive domain-containing protein 1A (ARID1A), ARID1B, SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), SMARCA2], observed in 66% (55 of 83) cases, was not of prognostic significance.
Conclusions: These results indicate that all molecular subtypes of DD/UDEC except POLEmut behave in an aggressive fashion. Further study is needed to determine whether these molecular alterations can be targeted with adjuvant therapy, in order to improve outcomes of patients with DD/UDEC.
{"title":"Prognostic values of molecular subtypes and SWI/SNF protein expression in de-differentiated/undifferentiated endometrial carcinoma.","authors":"Chae Young Shin, Bengul Gokbayrak, Valerie L Tao, Noorah Almadani, Eunice S Li, Rebecca Ho, Felix Kf Kommoss, Jutta Huvila, Derek Chiu, Samuel Leung, Basile Tessier-Cloutier, David G Huntsman, C Blake Gilks, Jessica N McAlpine, Lynn Hoang, Yemin Wang","doi":"10.1111/his.15411","DOIUrl":"https://doi.org/10.1111/his.15411","url":null,"abstract":"<p><strong>Aims: </strong>Classification and risk stratification of endometrial carcinoma (EC) has transitioned from histopathological features to molecular classification, e.g. the ProMisE classifier, identifying four prognostic subtypes: POLE mutant (POLEmut) with almost no recurrence or disease-specific death events, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP), with intermediate outcome and p53 abnormal (p53abn) with poor outcomes. However, the applicability of molecular classification is unclear in rare but aggressive histotypes of EC, e.g. de-differentiated and undifferentiated endometrial cancers (DD/UDEC). Here, we aim to assembled a cohort of DD/UDEC from a single institution and analysed the prognostic significance of ProMisE molecular subtypes and the expression of SWItch/sucrose non-fermentable (SWI/SNF) chromatin remodelling complex members, previously implicated in the pathogenesis of DD/UDEC.</p><p><strong>Methods and results: </strong>We accrued 88 DD/UDEC cases, assessed POLE status by Sanger sequencing and performed immunohistochemistry for p53, mismatch repair and SWI/SNF proteins on the tissue microarrays assembled. Assignment of molecular subtypes was possible in 80 tumours; POLE sequencing failed in the remaining eight cases. There were 12 (15%) POLEmut, 44 (55%) MMRd, 14 (17.5%) p53abn and 10 (12.5%) NSMP DD/UDEC. POLEmut DD/UDECs had excellent outcomes, but the other three molecular subtypes all had poor outcomes, with no significant differences among them. The loss of one or more SWI/SNF proteins [AT-rich interactive domain-containing protein 1A (ARID1A), ARID1B, SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), SMARCA2], observed in 66% (55 of 83) cases, was not of prognostic significance.</p><p><strong>Conclusions: </strong>These results indicate that all molecular subtypes of DD/UDEC except POLEmut behave in an aggressive fashion. Further study is needed to determine whether these molecular alterations can be targeted with adjuvant therapy, in order to improve outcomes of patients with DD/UDEC.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abrar Ashi, Aeshah A Awaji, Jacquelyn Bond, Colin A Johnson, Abeer M Shaaban, Sandra M Bell
Aims: Threonine and tyrosine kinase (TTK) is up-regulated in triple-negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment-naïve pre-treatment cores and paired pre- and post-NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.
Methods and results: Transcriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis. TTK protein expression was evaluated using immunohistochemistry staining, employing receiver operating characteristic curve analysis to determine an optimal TTK expression cut-off point. The association between TTK expression, clinicopathological parameters and survival outcomes was examined. Additionally, MCPH1 protein expression was assessed in a pilot study. Analysis revealed a significantly elevated TTK mRNA expression in BC tissue compared to normal breast tissue, with high TTK mRNA levels predicting reduced overall survival. Notably, TTK protein expression increased significantly post-NACT in a paired cohort. Conversely, decreased TTK protein expression pre-NACT was correlated with improved overall survival.
Conclusions: High TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1-deficient cancer cells.
{"title":"Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting.","authors":"Abrar Ashi, Aeshah A Awaji, Jacquelyn Bond, Colin A Johnson, Abeer M Shaaban, Sandra M Bell","doi":"10.1111/his.15399","DOIUrl":"https://doi.org/10.1111/his.15399","url":null,"abstract":"<p><strong>Aims: </strong>Threonine and tyrosine kinase (TTK) is up-regulated in triple-negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment-naïve pre-treatment cores and paired pre- and post-NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.</p><p><strong>Methods and results: </strong>Transcriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis. TTK protein expression was evaluated using immunohistochemistry staining, employing receiver operating characteristic curve analysis to determine an optimal TTK expression cut-off point. The association between TTK expression, clinicopathological parameters and survival outcomes was examined. Additionally, MCPH1 protein expression was assessed in a pilot study. Analysis revealed a significantly elevated TTK mRNA expression in BC tissue compared to normal breast tissue, with high TTK mRNA levels predicting reduced overall survival. Notably, TTK protein expression increased significantly post-NACT in a paired cohort. Conversely, decreased TTK protein expression pre-NACT was correlated with improved overall survival.</p><p><strong>Conclusions: </strong>High TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1-deficient cancer cells.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenwen Zhang, Yiling Song, Haiyan Shi, Bingjian Lu
Aims: Our study aimed to further confirm the clinical significance of the tumour budding activity and cell nest size-based (TBNS) grading scheme in cervical squamous cell carcinomas (SCC).
Methods and results: We applied the TBNS system to assess the prognostic value in an institutional cohort of well-annotated cervical SCC consisting of 312 consecutive cases with surgical resection, no neoadjuvant chemotherapy and higher than stage pT1a. We found that high budding activity, single cell and TBNS grade 3 were more frequently associated with a decreased overall survival (OS) time and disease-free survival (DFS) time (P < 0.001) and several other clinicopathological factors, including lymphovascular space invasion, lymph node metastasis, advanced Federation of Gynecology and Obstetrics (FIGO) stage and deep invasion of the cervical wall (> 2/3) (P < 0.05). On multivariate analysis, TBNS grade 3 was an adverse indicator for OS and DFS independently of age, invasion of the cervical wall and FIGO stage (P < 0.05). By comparison, the conventional three-tiered grading system was not associated with OS and DFS in cervical SCC (P > 0.05).
Conclusions: Our study further confirms that the TBNS grading scheme is robust in prognostic assessment in cervical SCC that outperforms the conventional three-tiered grading system. It is applicable to add TBNS grade into routine diagnostic practice.
{"title":"Further confirmation of a highly prognostic grading scheme based upon tumour budding and cell cluster size in cervical squamous cell carcinoma.","authors":"Wenwen Zhang, Yiling Song, Haiyan Shi, Bingjian Lu","doi":"10.1111/his.15404","DOIUrl":"https://doi.org/10.1111/his.15404","url":null,"abstract":"<p><strong>Aims: </strong>Our study aimed to further confirm the clinical significance of the tumour budding activity and cell nest size-based (TBNS) grading scheme in cervical squamous cell carcinomas (SCC).</p><p><strong>Methods and results: </strong>We applied the TBNS system to assess the prognostic value in an institutional cohort of well-annotated cervical SCC consisting of 312 consecutive cases with surgical resection, no neoadjuvant chemotherapy and higher than stage pT1a. We found that high budding activity, single cell and TBNS grade 3 were more frequently associated with a decreased overall survival (OS) time and disease-free survival (DFS) time (P < 0.001) and several other clinicopathological factors, including lymphovascular space invasion, lymph node metastasis, advanced Federation of Gynecology and Obstetrics (FIGO) stage and deep invasion of the cervical wall (> 2/3) (P < 0.05). On multivariate analysis, TBNS grade 3 was an adverse indicator for OS and DFS independently of age, invasion of the cervical wall and FIGO stage (P < 0.05). By comparison, the conventional three-tiered grading system was not associated with OS and DFS in cervical SCC (P > 0.05).</p><p><strong>Conclusions: </strong>Our study further confirms that the TBNS grading scheme is robust in prognostic assessment in cervical SCC that outperforms the conventional three-tiered grading system. It is applicable to add TBNS grade into routine diagnostic practice.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aims: The hepatic perivascular epithelioid cell tumour (PEComa), including angiomyolipoma, exhibits diverse morphology and clinical behaviour; however, its prognostic features remain undefined. This study aimed to investigate its histological features and prognostic factors.
Methods and results: In total, 132 patients were included. Clinical data and histopathological slides were assessed along with the p53 and Ki-67 immunohistochemistry. Targeted next-generation sequencing was performed in three cases. Based on the histologic subtypes, 7 (10%), 36 (51%), 13 (18%), and 15 (21%) patients were classified as inflammatory angiomyolipoma, conventional angiomyolipoma, epithelioid angiomyolipoma, and PEComa not otherwise specified (NOS), respectively, among 71 patients who underwent surgical resection. We proposed the risk prediction criteria after defining primary tumour size ≥7 cm, infiltrative border, mitotic rate >1/10 mm2, necrosis, vascular invasion, and PEComa NOS as worrisome features, as follows: high-risk: ≥3 worrisome features; intermediate-risk: 1-2 features; low-risk: none of the features. Applying these criteria, 4 (6%), 31 (44%), and 36 (51%) patients were classified into high-, intermediate-, and low-risk groups, respectively. One patient each in the high-risk (25%) and intermediate-risk (3%) groups developed peritoneal metastases and intrahepatic recurrence, respectively, whereas none in the low-risk group showed disease progression. A literature review of clinically malignant hepatic PEComa family tumours was conducted, and upon application of our criteria, 62% (16/26) of the patients were classified as high-risk and 35% (9/26) as intermediate- or high-risk.
Conclusion: Our risk prediction criteria can effectively predict the clinical outcomes in primary hepatic PEComa.
{"title":"Risk prediction criteria for the primary hepatic perivascular epithelioid cell tumour family, including angiomyolipoma: analysis of 132 cases with a literature review.","authors":"Youngeun Yoo, Jihun Kim, In Hye Song","doi":"10.1111/his.15405","DOIUrl":"https://doi.org/10.1111/his.15405","url":null,"abstract":"<p><strong>Aims: </strong>The hepatic perivascular epithelioid cell tumour (PEComa), including angiomyolipoma, exhibits diverse morphology and clinical behaviour; however, its prognostic features remain undefined. This study aimed to investigate its histological features and prognostic factors.</p><p><strong>Methods and results: </strong>In total, 132 patients were included. Clinical data and histopathological slides were assessed along with the p53 and Ki-67 immunohistochemistry. Targeted next-generation sequencing was performed in three cases. Based on the histologic subtypes, 7 (10%), 36 (51%), 13 (18%), and 15 (21%) patients were classified as inflammatory angiomyolipoma, conventional angiomyolipoma, epithelioid angiomyolipoma, and PEComa not otherwise specified (NOS), respectively, among 71 patients who underwent surgical resection. We proposed the risk prediction criteria after defining primary tumour size ≥7 cm, infiltrative border, mitotic rate >1/10 mm<sup>2</sup>, necrosis, vascular invasion, and PEComa NOS as worrisome features, as follows: high-risk: ≥3 worrisome features; intermediate-risk: 1-2 features; low-risk: none of the features. Applying these criteria, 4 (6%), 31 (44%), and 36 (51%) patients were classified into high-, intermediate-, and low-risk groups, respectively. One patient each in the high-risk (25%) and intermediate-risk (3%) groups developed peritoneal metastases and intrahepatic recurrence, respectively, whereas none in the low-risk group showed disease progression. A literature review of clinically malignant hepatic PEComa family tumours was conducted, and upon application of our criteria, 62% (16/26) of the patients were classified as high-risk and 35% (9/26) as intermediate- or high-risk.</p><p><strong>Conclusion: </strong>Our risk prediction criteria can effectively predict the clinical outcomes in primary hepatic PEComa.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aaron Auerbach, John J Schmieg, Mary Klassen, Ann Nelson, Nadine S Aguilera
The resurgence of measles, syphilis, and HIV presents a significant threat to global health, especially in the wake of the COVID-19 pandemic. These three infections involve lymph nodes and have unique pathologic findings in lymph nodes. We explore the pathological and clinical characteristics of these infections, focusing on their involvement of lymph nodes and their pathologic diagnosis in lymph node specimens. For HIV, lymph nodes are sites of viral replication and reservoirs, and the disease demonstrates multiple patterns within lymph nodes. The recent increase in measles, due in part to declining vaccination rates, signals the need for pathologists to be able to identify the characteristic Warthin-Finkeldey cells present in lymph node specimens. Syphilis, a reemerging sexually transmitted infection, often presents with lymphadenopathy and can mimic other conditions, complicating clinical diagnosis. By revisiting well-established findings and presenting new insights into the histopathological changes within lymphoid tissues, this review provides essential knowledge for pathologists and clinicians to improve diagnostic accuracy and treatment outcomes.
{"title":"HIV, measles, and syphilis: histopathologic characteristics of lymphatic system involvement of three reemerging infectious diseases.","authors":"Aaron Auerbach, John J Schmieg, Mary Klassen, Ann Nelson, Nadine S Aguilera","doi":"10.1111/his.15408","DOIUrl":"https://doi.org/10.1111/his.15408","url":null,"abstract":"<p><p>The resurgence of measles, syphilis, and HIV presents a significant threat to global health, especially in the wake of the COVID-19 pandemic. These three infections involve lymph nodes and have unique pathologic findings in lymph nodes. We explore the pathological and clinical characteristics of these infections, focusing on their involvement of lymph nodes and their pathologic diagnosis in lymph node specimens. For HIV, lymph nodes are sites of viral replication and reservoirs, and the disease demonstrates multiple patterns within lymph nodes. The recent increase in measles, due in part to declining vaccination rates, signals the need for pathologists to be able to identify the characteristic Warthin-Finkeldey cells present in lymph node specimens. Syphilis, a reemerging sexually transmitted infection, often presents with lymphadenopathy and can mimic other conditions, complicating clinical diagnosis. By revisiting well-established findings and presenting new insights into the histopathological changes within lymphoid tissues, this review provides essential knowledge for pathologists and clinicians to improve diagnostic accuracy and treatment outcomes.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maximilian N Kinzler, Steffen Gretser, Falko Schulze, Katrin Bankov, Nada Abedin, Wolf O Bechstein, Fabian Finkelmeier, Stefan Zeuzem, Henning Reis, Peter J. Wild, Dirk Walter