Endocrine-related cancer最新文献

{"title":"Management of patients with small pancreatic neuroendocrine tumors from a biomarker and surgical perspective.","authors":"Anna Vera D Verschuur, Lin Chen, Els J Nieveen van Dijkum, Claudio Luchini, Thorvardur R Halfdanarson, Seung-Mo Hong, Aatur D Singhi, Lodewijk A A Brosens, Christopher M Heaphy","doi":"10.1530/ERC-24-0305","DOIUrl":"10.1530/ERC-24-0305","url":null,"abstract":"<p><p>Pancreatic neuroendocrine tumors (PanNETs) have an age-adjusted incidence of 1.5 per 100,000 people, with a notable rise in the incidence of small (≤2 cm) non-functional PanNETs (NF-PanNETs) in recent decades. While surgery is traditionally the preferred treatment for localized NF-PanNETs, active surveillance is now an accepted management strategy for tumors smaller than 2 cm due to their relatively benign behavior. However, this approach has not yet been fully integrated into routine clinical practice. There is considerable histopathological heterogeneity observed in NF-PanNETs, which results in significant variability in clinical presentation, behavior and treatment outcomes. Hence, tumor size alone does not provide sufficient certainty regarding a benign clinical course for decision-making. Although studies advocate for incorporating WHO grade into clinical prognostic assessments, this marker also has limitations. Several established tissue-based markers, such as ATRX and DAXX alterations, alternative lengthening of telomeres, and copy number variations, can be used for PanNET subtyping and correlate with metastatic risk. Combining these markers with traditional histopathological parameters may yield a more comprehensive and accurate prognostic assessment. This review discusses the advantages and limitations of current prognostication methods for small NF-PanNETs and highlights recently established prognostic markers, along with the requirements for their implementation into routine clinical practice. It also proposes practical solutions to address the challenges associated with the immediate integration of these biomarkers into routine care.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11997717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of prognostic factors in advanced pediatric ACC.","authors":"Maria Riedmeier, Shipra Agarwal, Sonir R R Antonini, Saniye Ekinci, Martin Fassnacht, Bonald Cavalcante Figueiredo, Christoph Härtel, Jagdish Prasad Meena, Stephen D Marks, Jessica Munarin, Soraya Puglisi, Gerdi Tuli, Bilgehan Yalcin, Paul G Schlegel, Armin Wiegering, Verena Wiegering","doi":"10.1530/ERC-24-0135","DOIUrl":"10.1530/ERC-24-0135","url":null,"abstract":"<p><p>Therapeutic options of advanced pediatric adrenocortical carcinoma (pACC) are limited, and achieving valuable risk stratification remains challenging. We refined the value of prognostic factors with an emphasis on resection status. Retrospective international data from 106 patients with advanced pACC from various collaborating centers of the international pACC working groups ENSAT-PACT, IC-PACT and/or from individual international collaboration diagnosed were collected. One hundred six patients aged 0.1-18.1 (median 7.6) years were diagnosed with pACC, with 42 tumor stage III and 64 stage IV, respectively. Eighty percent (85/106) of the tumors were hormone-producing, with a mean Ki67 index for both stage groups of 29%. Patient survival was 45% (48/106) with a mean follow-up of 17.7 months. Higher age, tumor stage IV and increased Ki67 index worsened the prognosis on overall survival. Resection status had an essential impact on survival, as the patients with R0 resection (n = 32) had a better overall survival (71% for stage III patients; 80% for stage IV patients) than patients with R1 (n = 24) (45% for stage III; 69% for stage IV), R2 (n = 33) (17% for stage III; 15% for stage IV) and Rx (n = 7) (0% for stage III; 17% for stage IV). Of the ten patients with tumor spillage, only a few (57% of stage III; 0% of stage IV patients) survived. The resection status has a significant impact on overall survival in pACC. Therefore, tumor surgery should only be undertaken by experienced surgeons proficient in adrenalectomy and oncology, ideally within specialized pediatric oncological centers with a multidisciplinary team setting.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation-based score in pediatric adrenocortical carcinoma.","authors":"Maria Riedmeier, Jan Idkowiak, Heidi Frey, Sonir R R Antonini, Gabriela Fernandes Luiz Canali, Carl Friedrich Classen, Nerea Domínguez-Pinilla, Martin Fassnacht, Steffen Fuchs, Christoph Härtel, Dominika Janús, Ronald de Krijger, Tezer Kutluk, Ngoc Lan Bui, Jagdish Prasad Meena, Mouna Mezoued, Jessica Munarin, Max M van Noesel, Nihal Özdemir Köse, Simon H Pearce, Thomas Perwein, Soraya Puglisi, Jaydira Del Rivero, Paul G Schlegel, Irene Schmid, Gerdi Tuli, Justyna Walenciak, Bilgehan Yalcin, Verena Wiegering","doi":"10.1530/ERC-24-0244","DOIUrl":"10.1530/ERC-24-0244","url":null,"abstract":"<p><p>Inflammation-based scores have been demonstrated to be independent prognostic factors in predicting outcomes in adult adrenocortical carcinoma (ACC). We aimed to investigate the prognostic role of these scores in pediatric adrenocortical carcinoma (pACC) patients. An international multicenter analysis was conducted on a pediatric cohort from 21 ACC centers. Pretreatment inflammation-based scoring parameters, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and serum albumin, as well as clinical parameters, were analyzed. The primary endpoint was 10-year overall survival (OS). One hundred twenty-nine pediatric patients (50.4% females, mean age 87 months) across all tumor stages with a median follow-up of 36 months were included. 107/108 patients underwent primary surgery, and 62/106 received systemic treatment at the time of diagnosis. Of 102 patients, 27 died from disease. In the univariable analysis, NLR ≥5 (HR 8.0, 95% CI 3.4-19.1), MLR ≥0.28 (HR 4.2, 95% CI 1.7-10.4), PLR ≥190 (HR 4.5, 95% CI 2.0-10.4) and dNLR ≥1.44 (HR 5.9, 95% CI 2.3-15.5), as well as clinical parameters age ≥4 years (HR 5.5, 95% CI 1.9-15.8), tumor stage IV (HR 5.7, 95% CI 2.7-11.9) and incomplete resection status (HR 8.0, 95% CI 3.6-17.7) were significantly associated with reduced 10-year OS. After multivariable adjustment, only tumor stage IV (HR 336.7, 95% CI 5.8-19,518.1) and MLR ≥0.28 (HR 247.1, 95% CI = 3.1-19,907.5) were significantly associated with an unfavorable outcome. Inflammation-based scores tend to have prognostic value in pACC and could serve as prognostic tools after further validation in future studies with sufficient case numbers.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12002726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited value of genetic profiling in guiding radioiodine therapy for metastatic differentiated thyroid cancer.","authors":"Ziyan He, Congcong Wang, Chang Liu, Ke Zhang, Junyao Wang, Xufu Wang, Yifan Zhang, Libo Chen","doi":"10.1530/ERC-24-0298","DOIUrl":"10.1530/ERC-24-0298","url":null,"abstract":"<p><p>Assessing the 131I-avidity of metastatic differentiated thyroid cancer (mDTC) is pivotal to characterizing the nature of disease and optimizing the therapeutic strategy. In this prospective study, the predictive value of genetic profiling of 18 selected thyroid cancer-relevant genes for 131I-avidity and the response to radioiodine therapy (RT) was studied in comparison with those of diagnostic 131I scan. During univariate analysis, BRAF status (odds ratio, (OR) = 12.47, 95% confidence interval (CI): 5.03-30.89, P < 0.001) and TNM-M stage (P = 0.029) were found to be associated with 131I-avidity, but multivariate analysis identified BRAF V600E as the sole independent factor associated with the non-131I-avidity (OR = 12.98, 95% CI: 3.77-44.73, P < 0.001). The predictive values of BRAF wild-type for 131I-avidity and BRAF V600E for non-131I-avidity were 84.6 and 69.4%, respectively, both lower than those of diagnostic 131I scan (positive predictive value of 100%, P = 0.031; negative predictive value of 81.1%, P = 0.219). The predictive value of BRAF V600E for non-131I-avidity was not significantly improved when combined with TERT promoter mutation (76.9 vs 69.4%, P = 0.736). Moreover, the predictive value of BRAF V600E for biochemical non-response was 70.8% (17/24), while no correlation was found between BRAF status and structural response. In contrast, a negative diagnostic 131I scan was significantly associated with both biochemical and structural non-responses, with predictive values of 81 and 100%, respectively. The current study demonstrated that genetic profiling is of limited value in guiding RT for mDTC, while a diagnostic 131I scan proved superior in this respect.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ob/ob obese mice promote tumorigenesis of endometrial cancer associated with Pten deficiency.","authors":"Keun Cheon Kim, Amanda Hull, Eric Johannsen, Mark I Hunter, Tae Hoon Kim, Jae-Wook Jeong","doi":"10.1530/ERC-24-0228","DOIUrl":"10.1530/ERC-24-0228","url":null,"abstract":"<p><p>Obesity refers to the condition of being overweight due to abnormal fat accumulation and is highly associated with the development of various cancers. Endometrial cancer is the most diagnosed gynecologic cancer. Obesity is a strong risk factor for endometrial cancer. However, the etiological and pathophysiological effects of obesity on endometrial cancer have not been fully understood. To determine the effect of obesity on tumorigenesis in endometrial cancer, we examined the effect of obesity on tumorigenesis using genetically engineered mouse models, including an obesity model (ob/ob), an endometrial cancer model (Pgrcre/+Ptenf/f ; Ptend/d ), and an endometrial cancer with obesity model (Pgrcre/+Ptenf/fob/ob; Ptend/dob/ob). Histopathological analysis was performed on the uteri of the three groups during tumorigenesis. From 1.5 months of age, the body and uterine weight of Ptend/dob/ob mice were significantly higher than those of the Ptend/d mice. Ptend/dob/ob mice had higher tumor grade with myometrial invasion at 1.5 and 2 months than Ptend/d mice. The levels of phospho-histone H3, a proliferation marker and phospho-STAT3 were significantly increased in the endometrial cancer of Ptend/dob/ob mice compared to Ptend/d mice. Our results suggest that obesity accelerates the progression of endometrial cancer associated with Pten mutation.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCL2 expression predicts clinical outcomes and regulates E-cadherin and angiogenesis in pituitary tumours.","authors":"Ana Luísa Silva, Sayka Barry, Mariana Lopes-Pinto, Rita Joaquim, Catarina Miranda, Fábio Reis, Micaella Miranda, Paulo Matos, Oniz Suleyman, Tiago Oliveira, Dolores López-Presa, Gonçalo Borrecho, Francisco Tortosa, Claúdia C Faria, Márta Korbonits, Pedro Marques","doi":"10.1530/ERC-24-0293","DOIUrl":"10.1530/ERC-24-0293","url":null,"abstract":"<p><p>The crosstalk between tumour cells and microenvironment components in pituitary neuroendocrine tumours (PitNETs), including chemokines, may impact tumour behaviour and clinical outcomes. CCL2 was previously identified as a key chemokine in PitNETs, but its role remains unknown. We aimed to study the role of CCL2 in defining the phenotype and clinical outcomes of PitNETs and in regulating macrophage chemotaxis, epithelial-to-mesenchymal transition (EMT) and angiogenesis. We studied CCL2 and E-cadherin expression, macrophages (CD68 and CD163) and vessels (CD31) in samples from 86 PitNET patients. Higher CCL2 mRNA expression was found in patients who required multimodal and multiple treatments and had active disease at the last follow-up. Higher CCL2 immunoreactivity was observed in patients with larger PitNETs. Among somatotroph tumours, CCL2 mRNA expression correlated with serum IGF-1 at the last follow-up. CCL2 mRNA expression levels correlated negatively with CDH1 expression and with E-cadherin complete membranous staining. In vitro, CCL2 downregulated E-cadherin expression in GH3 cells but did not affect cell morphology or migration. CCL2 expression correlated with the number of vessels, vessel perimeter and vessel area in PitNETs but not with PitNET-infiltrating macrophages. Our data suggest that CCL2 may lead to (or is at least a predictive marker of) poorer clinical outcomes and more difficult-to-treat PitNETs, potentially through its regulatory effects on different tumour-related mechanisms beyond immune cell chemotaxis, including in the activation of the EMT pathway and modulation of angiogenesis in PitNETs. Further studies are needed to corroborate our findings and to validate CCL2 as a potential predictive marker and therapeutic target in PitNETs.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, genetic, radiological characteristics and management of mediastinal paragangliomas: a literature review and case series.","authors":"Mark Quinn, Yasmine Kemkem, Gemma White, Phil Touska, Dimitra Christodoulou, Audrey Jacques, Louise Breen, Barbara McGowan, Mamta Joshi, Fahim Ul Hassan, Karen Harrison-Phipps, Johnathan G Hubbard, Rupert Obholzer, Louise Izatt, Paul Carroll, Anand Velusamy","doi":"10.1530/ERC-24-0279","DOIUrl":"10.1530/ERC-24-0279","url":null,"abstract":"<p><p>Paragangliomas (PGLs) are neuroendocrine tumours (NETs) that arise from neural crest-derived cells. Up to 40% of cases occur due to the presence of a pathogenic germline variant (PGV) in a known gene. Mediastinal PGLs are rare but are being diagnosed with increasing frequency. Treatment generally involves surgery but is complicated in mediastinal PGLs due to their anatomy. Here, we will perform a literature review and discuss our experience with 18 such cases. Cases were identified via the Guy's and St Thomas' NHS Foundation Trust NET multidisciplinary team database. Tumours ranged in size from 0.6 × 0.6 to 6.8 × 4.9 cm. 72.2% were associated with a PGV of SDHB or SDHD. 22.2% developed metastatic disease, but it was only possible to attribute 50% of these to a mediastinal primary. 68Ga-DOTATATE PET CT demonstrated 100% sensitivity. The literature review identified 233 cases. A PGV was reported in 81% of cases, with metastatic disease in approximately 39.2%. It was not possible to confirm that all cases of metastatic disease were secondary to a mediastinal primary. Our experience confirms the high rate of mediastinal PGLs arising in the presence of a PGV. The lower rate of metastatic disease in our cohort (11.1%) likely represents earlier diagnosis thanks to the application of screening protocols and the increased sensitivity of 68Ga-DOTATATE PET CT. With this increased sensitivity, we have diagnosed small mediastinal PGLs that were not evident on alternative imaging modalities. In the absence of growth or catecholamine secretion, the need to intervene on these is unclear.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased cancer risk in a cohort of patients with acromegaly in Israel.","authors":"Hadar Duskin-Bitan, Alon Perez, Doron Netzer, Arnon D Cohen, Doron Comaneshter, Tanya Beckenstein, Shlomit Yaron, Zaina Adnan, Yaron Rudman, Hiba Masri Iraqi, Ilan Shimon","doi":"10.1530/ERC-24-0087","DOIUrl":"10.1530/ERC-24-0087","url":null,"abstract":"<p><p>The association between acromegaly and cancer had been assessed mainly in population studies with inconsistent results. The objective of this study was to investigate the risk of cancer in a large cohort of patients with acromegaly compared with matched controls. The comprehensive computerized database of the largest healthcare provider organization in Israel was searched for patients diagnosed with acromegaly in 2000-2021. All diagnoses were qualitatively validated. Patients were individually matched 1:5 with a control group for age, sex and socioeconomic status. Clinical and outcome data were collected from medical files. The final cohort consisted of 470 patients (54% male) with acromegaly and 2,330 control subjects. The mean age at diagnosis was 53 years, and the mean duration of follow-up after diagnosis was 10.4 years. The prevalence of solid malignancies was 21.3% in the acromegaly group and 14.8% in the control group (OR 1.6, 95% CI 1.2-2.0). Patients with acromegaly had a higher rate of thyroid cancer (2.8 vs 0.6%; OR 5.1, CI 2.3-11.0) and a tendency for a higher risk of colorectal cancer (3.6 vs 2.8%; OR 1.3, CI 0.7-2.2), prostate cancer (2.8 vs 1.7%; OR 1.6, CI 0.8-3.1) and renal cancer (1.5 vs 0.8%; OR 1.8, CI 0.8-4.4), but not hematological malignancies. They also had a higher mortality rate (21.3 vs 15.7%; OR 1.5, CI 1.1-1.9). In conclusion, the higher prevalence of malignant solid tumors in patients with acromegaly compared with control subjects suggests that periodic screening for early detection of solid cancers may be considered in this patient population.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mannose enhances anti-tumor effect of PLX4032 in anaplastic thyroid cancer.","authors":"Zhuolin Li, Liumei Song, Yuanxing Yang, Yang Zhao, Sharui Ma","doi":"10.1530/ERC-24-0209","DOIUrl":"10.1530/ERC-24-0209","url":null,"abstract":"<p><p>Anaplastic thyroid cancer represents the most aggressive form of thyroid cancer and harbors BRAF mutations in over 40% of cases. Vemurafenib (PLX4032), a BRAF kinase inhibitor, shows promise in BRAFV600E-positive advanced thyroid cancer but may promote resistance in anaplastic cases. This study investigates whether mannose, known to selectively inhibit thyroid cancer, enhances PLX4032 efficacy. To evaluate whether mannose could enhance the response of anaplastic thyroid cancer cells to vemurafenib, we employed several in vitro assays, including MTT, colony formation, flow cytometry, migration and invasion assays. In addition, we performed in vivo assays using mouse models with subcutaneous xenografts. Our findings demonstrated that vemurafenib and mannose synergistically inhibit anaplastic thyroid cancer cell proliferation. The combined treatment significantly impeded anaplastic thyroid cancer cell migration and invasion while promoting apoptosis. In vivo studies corroborated these observations. The underlying mechanism by which mannose potentiates the antitumor effects of vemurafenib was explored using the Seahorse XFe96 Analyzer to measure glycolysis parameters and Western blotting to assess the expression of associated proteins. Mechanistically, vemurafenib reduced the expression of ZIP10, which in turn decreased the enzyme activity of phosphomannose isomerase. This suppression of ZIP10 enhanced mannose-mediated inhibition of glycolysis and thus its antitumor effect, as confirmed by rescue experiments with ZIP10 overexpression. The resulting decrease in glycolysis led to lower ATP levels, which are essential for the phosphorylation of ERK and AKT. Therefore, the combination of vemurafenib and mannose inhibited the levels of pERK and pAKT, thereby improving the effectiveness of PLX4032 in treating anaplastic thyroid cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype of pheochromocytoma and paraganglioma by germline mutation: a Korean multicenter study.","authors":"Min Jeong Park, Seung Shin Park, Bon Hyang Lee, Jin Sun Jang, Won Woong Kim, Su Jin Kim, Yu-Mi Lee, Kyu Eun Lee, Tae-Yon Sung, Moon-Woo Seong, Woochang Lee, Jung-Min Koh, Jung Hee Kim, Seung Hun Lee","doi":"10.1530/ERC-24-0269","DOIUrl":"10.1530/ERC-24-0269","url":null,"abstract":"<p><p>Recent advances in genetic testing have challenged the traditional genotype-phenotype correlation in pheochromocytomas and paragangliomas (PPGL). We aimed to characterize the genotype-phenotype correlations in PPGL in a large Korean cohort and compare our findings with those from other countries. We retrospectively analyzed 627 patients with PPGL from two centers who underwent genetic testing for germline pathogenic variants (PVs) from 2000 to 2023 to examine the prevalence of clusters and their correlation with specific phenotypes. Moreover, we systematically reviewed 44 studies that investigated the frequency of germline PVs based on geographical differences. Germline PVs were identified in 29.7% of patients (n = 186). The prevalence of cluster 1A, 1B and 2 PVs was 10.6% (n = 67), 8.0% (n = 50) and 11.1% (n = 69), respectively. Cluster 1 patients were presented with more aggressive features, including younger age at diagnosis (39 years), higher rates of extra-adrenal (44.4%), and metastatic (27.8%) tumors, than did the wild-type and cluster 2 groups (P < 0.001). Cluster 1A patients had significantly higher metastasis rates than cluster 1B patients (38.8 vs 12.5%; P < 0.001). The cluster 2 group showed a high recurrence risk but rarely developed metastases. The cluster 1-to-cluster 2 ratio among Koreans (1.7) was lower than that among Europeans (2.9) and North Americans (3.3). This study underscores the genetic and clinical heterogeneity of PPGL among Korean patients based on genetic clusters and highlights geographic variations in PVs. These findings have significant implications for risk stratification, surveillance and management strategies for patients with PPGL.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}