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1.
Saudi Med J ; 45(6): 560-564, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38830650

ABSTRACT

OBJECTIVES: To analyze the immunohistochemical staining pattern of mismatch repair (MMR) proteins and p53 in endometrial carcinoma cases, including different subtypes and stages, to gain insights into their role in the pathogenesis and clinical behaviour of this malignancy. METHODS: In this study, we investigate the association between MMR deficiency, p53 mutational status, and clinical outcomes in various subtypes of endometrial carcinoma. The immunohistochemical staining pattern of MMR proteins in 96 cases of endometrial carcinoma have been analyzed, including 72 endometrioid, 14 papillary serous, 5 clear cell, and 5 mixed Müllerian tumor. RESULTS: The results showed that 36 cases were MMR deficient, with the majority being of endometrioid subtype. The p53 immunostain showed a mutational pattern in a subset of cases, with a documented dismal prognosis. However, aforementioned stains failed to predict synchronous or metachronous cancers in 5 patients. CONCLUSION: These findings highlight the importance of MMR and p53 immunohistochemical staining in the classification, and prognosis of endometrial carcinoma.


Subject(s)
DNA Mismatch Repair , Endometrial Neoplasms , Immunohistochemistry , Tumor Suppressor Protein p53 , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/genetics , Tumor Suppressor Protein p53/metabolism , Middle Aged , Aged , Adult , Prognosis , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/metabolism , Mutation , Aged, 80 and over
2.
JCO Glob Oncol ; 10: e2300393, 2024 May.
Article in English | MEDLINE | ID: mdl-38754054

ABSTRACT

PURPOSE: Ovarian cancer can be categorized into distinct histologic subtypes with varying identifiable risk factors, molecular composition, clinical features, and treatment. The global incidence of ovarian cancer subtypes remains limited, especially in low- and middle-income countries (LMICs) without high-quality cancer registry systems. MATERIALS AND METHODS: We used data from population-based cancer registries of the Cancer Incidence in Five Continents project to calculate the proportions of serous, mucinous, endometrioid, clear cell, and other histologic subtypes of ovarian cancer. Proportions were applied to the estimated numbers of patients with ovarian cancer from Global Cancer Observatory 2020. Age-standardized incidence rates were calculated. RESULTS: Globally, an estimated 133,818 new patients of serous cancer, 35,712 new patients of mucinous cancer, 29,319 new patients of endometrioid cancer, and 17,894 new patients of clear cell cancer were identified in 2020. The distribution of ovarian cancer histologic subtypes exhibited regional variation. Eastern Europe had the highest rate of serous and mucinous carcinomas, whereas Northern Africa and Eastern Asia had the highest burden of endometrioid and clear cell carcinomas, respectively. CONCLUSION: This study provides a global incidence landscape of histologic subtypes of ovarian cancer, particularly in LMICs lacking comprehensive registry systems. Our analysis offers valuable insights into disease burden and guidance for tailored strategies for prevention of ovarian cancer.


Subject(s)
Ovarian Neoplasms , Registries , Humans , Female , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Registries/statistics & numerical data , Incidence , Middle Aged , Global Health/statistics & numerical data , Adult , Aged , Adenocarcinoma, Mucinous/epidemiology , Adenocarcinoma, Mucinous/pathology , Carcinoma, Endometrioid/epidemiology , Carcinoma, Endometrioid/pathology , Adenocarcinoma, Clear Cell/epidemiology , Adenocarcinoma, Clear Cell/pathology
3.
Cancer Med ; 13(10): e7216, 2024 May.
Article in English | MEDLINE | ID: mdl-38752451

ABSTRACT

BACKGROUND: To find the factors impacting overall survival (OS) prognosis in patients with endometrioid endometrial carcinoma (EEC) and adenocarcinoma and to establish a nomogram model to validate the 2023 International Federation of Obstetrics and Gynecology (FIGO) staging system for endometrial cancer. METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) training cohort. An independent validation cohort was obtained from the First Affiliated Hospital of Anhui Medical University between 2008 and 2023. Cox regression analysis identified independent prognostic factors for OS in EEC and adenocarcinoma patients. A nomogram predicting OS was developed and validated utilizing the C-index, calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). The relationship between the tumor grade and prognosis of EEC and adenocarcinoma was quantified using net reclassification improvement (NRI), propensity score matching (PSM), and Kaplan-Meier curves. RESULTS: Cox regression analysis identified age, race, marital status, tumor grade, tumor stage, tumor size, and chemotherapy as independent prognostic factors for OS. A nomogram for predicting OS was developed based on these factors. The C-indexes for the OS nomogram was 0.743 and 0.720 for the SEER training set and external validation set, respectively. The area under the ROC (AUC) for the OS nomogram was 0.755, 0.757, and 0.741 for the SEER data subsets and 0.844, 0.719, and 0.743 for the external validation subsets. Calibration plots showed high concordance between the nomogram-predicted and observed OS. DCA also demonstrated the clinical utility of the OS nomogram. NRI, PSM, and survival analyses revealed that tumor grade was the most important histopathological factor for EEC and adenocarcinoma prognosis. CONCLUSION: Seven independent prognostic variables for the OS of patients with EEC and adenocarcinoma were identified. The established OS nomogram has good predictive ability and clinical utility and validates the 2023 endometrial cancer FIGO staging system.


Subject(s)
Adenocarcinoma , Carcinoma, Endometrioid , Endometrial Neoplasms , Neoplasm Staging , Nomograms , SEER Program , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/mortality , Middle Aged , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/mortality , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Aged , Prognosis , ROC Curve , Neoplasm Grading , Adult , Kaplan-Meier Estimate
4.
PLoS One ; 19(5): e0304420, 2024.
Article in English | MEDLINE | ID: mdl-38805498

ABSTRACT

INTRODUCTION: This study aimed to assess the localization of chondroitin sulfate (CS), a primary extracellular matrix component, in the stromal region of endometrial carcinoma (EC). METHODS: Immunostaining was performed on 26 endometrial endometrioid carcinoma (EEC) samples of different grades and 10 endometrial serous carcinoma (ESC) samples to evaluate CS localization. This was further confirmed by Alcian Blue (AB) staining as well. RESULTS: In the G1-EEC samples, CS showed reactivity with fibrovascular stroma, supporting closely packed glandular crowding and papillary structures. As the grade increased, the original interstitial structure was re-established, and the localization of CS in the perigulandular region decreased. In the ESC samples, the thick fibrous strands supporting the papillary architecture showed reactivity with CS; however, the delicate stromal region branching into the narrow region showed poor reactivity. The AB staining results showed similar characteristics to the immunostaining ones. CONCLUSIONS: The characteristic localization of CS in various EC types was elucidated. The present study provides new information on endometrial stromal assessment.


Subject(s)
Chondroitin Sulfates , Endometrial Neoplasms , Humans , Female , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Endometrial Neoplasms/diagnosis , Chondroitin Sulfates/metabolism , Chondroitin Sulfates/analysis , Middle Aged , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/metabolism , Aged , Immunohistochemistry
5.
Klin Onkol ; 38(2): 126-133, 2024.
Article in English | MEDLINE | ID: mdl-38697821

ABSTRACT

BACKGROUND: While total hysterectomy and bilateral salpingo-oophorectomy without lymph node staging are standard for low- and intermediate-risk endometrial cancer, certain histopathologic factors revealed after surgery can necessitate additional interventions. Our study assessed the influence of sentinel lymph node biopsy on postoperative decision-making. MATERIALS AND METHODS: In the SENTRY trial (July 2021 - February 2023), we enrolled patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IA-IB low-grade endometrioid endometrial cancer. Laparoscopic sentinel lymph node mapping using indocyanine green was performed alongside total hysterectomy with bilateral salpingo-oophorectomy. Subsequent management changes based on sentinel lymph node biopsy results were evaluated. The trial was registered at ClinicalTrials.gov (NCT04972682). RESULTS: Of the 100 enrolled participants, a bilateral detection rate of 91% was observed with a median detection time of 10 min (interquartile range 8-13 min). Sentinel lymph node metastases were found in 8% (N = 8) of participants. Postoperative FIGO staging increased in 15% (N = 15) and decreased in 5% (N = 5) of patients. Sentinel lymph node biopsy results altered the adjuvant treatment plan for 20% (N = 20): external beam radiotherapy was omitted in 12% (N = 12) while 6% (N = 6) had external beam radiotherapy +/- systemic chemotherapy added due to sentinel lymph node metastases. In 2% (N = 2), the external beam radiotherapy field was expanded with the paraaortic region. No intraoperative complications were reported and no 30-day major morbidity and mortality occurred. Throughout a median follow-up of 14 (95% CI 12-15 months, neither patient-reported lymphedema nor pelvic recurrence surfaced in the cohort. CONCLUSIONS: Sentinel lymph node biopsy using indocyanine green is a safe procedure and allows tailoring adjuvant therapy in presumed low- and intermediate-risk endometrial cancer. It assists in avoiding external beam radiotherapy overtreatment and introducing additional modalities when necessary.


Subject(s)
Endometrial Neoplasms , Sentinel Lymph Node Biopsy , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Endometrial Neoplasms/therapy , Middle Aged , Hysterectomy , Aged , Salpingo-oophorectomy , Indocyanine Green , Neoplasm Staging , Lymphatic Metastasis , Postoperative Care , Laparoscopy , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/surgery , Carcinoma, Endometrioid/therapy
6.
Rev Assoc Med Bras (1992) ; 70(5): e20231115, 2024.
Article in English | MEDLINE | ID: mdl-38775501

ABSTRACT

OBJECTIVE: Endometrial cancer is the most common gynecological cancer in developed countries, with a majority of cases being low-grade endometrioid endometrial cancer. Identifying risk factors for disease recurrence and poor prognosis is critical. This study aimed to assess the correlation between preoperative cancer antigen-125 levels and disease recurrence in early-stage endometrioid endometrial cancer patients. METHODS: The study was a retrospective analysis of 217 patients diagnosed with endometrioid endometrial cancer who underwent surgical treatment at a university-affiliated tertiary hospital between 2016 and 2022. Patients were divided into two groups based on their preoperative cancer antigen-125 levels and compared with clinicopathological findings and disease recurrence. Disease-free survival rates were calculated, and logistic regression analysis was performed to determine independent factors affecting disease-free survival. RESULTS: The mean age of patients was 61.59±0.75 years, and the mean follow-up time was 36.95±1.18 months. The mean cancer antigen-125 level was 27.80±37.81 IU/mL. The recurrence rate was significantly higher in the group with elevated cancer antigen-125 levels (p=0.025). Disease-free survival was lower in patients with elevated cancer antigen-125 compared with those with normal levels (p=0.005). Logistic regression analysis revealed that elevated cancer antigen-125 levels were associated with disease recurrence (OR: 3.43, 95%CI 1.13-10.37, p=0.029). CONCLUSION: The findings of this study suggest that preoperative cancer antigen-125 levels can be used as a predictor of disease recurrence in early-stage endometrioid endometrial cancer patients. cancer antigen-125 levels may be a useful tool for risk stratification and patient management in endometrial cancer.


Subject(s)
CA-125 Antigen , Endometrial Neoplasms , Neoplasm Recurrence, Local , Neoplasm Staging , Humans , Female , Endometrial Neoplasms/blood , Endometrial Neoplasms/pathology , Endometrial Neoplasms/mortality , Endometrial Neoplasms/surgery , Middle Aged , Retrospective Studies , Neoplasm Recurrence, Local/blood , CA-125 Antigen/blood , Risk Factors , Disease-Free Survival , Preoperative Period , Carcinoma, Endometrioid/blood , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/mortality , Aged , Biomarkers, Tumor/blood , Prognosis
7.
Oncology (Williston Park) ; 38(5): 191-193, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38776516

ABSTRACT

Well-differentiated papillary mesothelioma (WDPM) is a rare mesothelial tumor of uncertain malignant potential. We present a unique case of a woman with synchronous WDPM and well-differentiated endometrioid adenocarcinoma (EA) arising from extraovarian endometriosis. A 56-year-old postmenopausal woman presented with a several-month history of right lower quadrant abdominal pain. She had a history of supracervical hysterectomy and bilateral salpingo-oophorectomy secondary to endometriosis. Imaging reported a mass in the right lower quadrant originating from the distal ileum. At laparotomy, the patient underwent a right colectomy with resection of the terminal ileum and excision of a solitary peritoneal nodule. Pathology was consistent with a diagnosis of well-differentiated EA (arising from extraovarian endometriosis) and WDPM. Further treatment consisted of complete surgical staging/debulking and adjuvant chemotherapy directed toward metastatic well-differentiated EA. Surgeons should be familiar with WDPM as a potential finding in women of reproductive age undergoing abdominal surgery for any indication.


Subject(s)
Carcinoma, Endometrioid , Endometriosis , Humans , Female , Middle Aged , Endometriosis/complications , Endometriosis/pathology , Endometriosis/surgery , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/surgery , Mesothelioma/pathology , Mesothelioma/surgery , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/surgery , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery
8.
Nat Genet ; 56(4): 637-651, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38565644

ABSTRACT

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.


Subject(s)
Carcinoma, Endometrioid , Endometrial Hyperplasia , Endometrial Neoplasms , Fertility Preservation , Proteogenomics , Humans , Female , Progestins/therapeutic use , Antineoplastic Agents, Hormonal , Endometrial Hyperplasia/drug therapy , Fertility Preservation/methods , Retrospective Studies , Carcinoma, Endometrioid/drug therapy , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology
9.
In Vivo ; 38(3): 1260-1265, 2024.
Article in English | MEDLINE | ID: mdl-38688602

ABSTRACT

BACKGROUND/AIM: Endometrial cancer (EC) is the predominant malignancy among gynecologic cancers and ranks fourth among all types of cancer. Recently, researchers have focused on the development of new prognostic biomarkers. Subunits of the SWI/SNF protein complex, like the ARID1 and BRG1, have been associated with the development of endometrial cancer. The present study aimed to evaluate the expression patterns of ARID1A and BRG1 in a collection of endometrioid adenocarcinomas of the uterus using immunohistochemistry. PATIENTS AND METHODS: The study comprised a total of thirty-three individuals diagnosed with stage I endometrioid endometrial cancer, treated with radical hysterectomy. The histological material was then examined to assess the cytoplasmic and nuclear expression of the proteins. RESULTS: ARID1A exhibited expression in both the cytoplasm and nucleus of cancer cells, whereas BRG1 was mainly expressed in the nuclei. In addition, ARID1A exhibited a notable decrease in expression in grade 3 histology, with no significant correlation with the depth of myometrial invasion. The reduced expression was highly related to tumor expansion into the endocervix. The findings demonstrated a total absence of ARID1A expression in 27% of endometrioid carcinomas, with a significant reduction in expression in an additional 51% of cancer cells. These findings align with the most recent published data. In contrast, in the current study, BRG1 was rarely down-regulated and was extensively expressed in the majority of endometrioid carcinomas, preventing the possibility of statistical analysis. CONCLUSION: In summary, ARID1A expression loss can be used as a biomarker to guide post-operative therapy; however, further investigation is needed, especially for early-stage endometrial cancer.


Subject(s)
Biomarkers, Tumor , DNA Helicases , DNA-Binding Proteins , Endometrial Neoplasms , Immunohistochemistry , Nuclear Proteins , Transcription Factors , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , DNA Helicases/genetics , DNA Helicases/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Middle Aged , Aged , Biomarkers, Tumor/metabolism , Neoplasm Staging , Prognosis , Gene Expression Regulation, Neoplastic , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/genetics , Adult , Neoplasm Grading
10.
Eur J Surg Oncol ; 50(6): 108317, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38581756

ABSTRACT

INTRODUCTION: The aim of this study was to assess the accuracy of a preoperative screening algorithm in identifying low-risk endometrial cancer (EC) patients to ensure optimal care. METHODS: A total of 277 patients with primary EC confirmed through biopsy underwent magnetic resonance imaging (MRI). Patients with risk factors for advanced high-risk EC, such as non-endometrioid histology, high-grade differentiation status, deep myometrial invasion, or spread beyond the uterine corpus, were systematically excluded. The remaining preoperatively screened patients with stage IA low-grade endometrioid EC (EEC) (n = 93) underwent surgery in a tertiary hospital. The accuracy of the preoperative diagnosis was evaluated by comparing the findings with the postoperative histopathological results. Disease-free survival (DFS) and overall survival (OS) were analyzed using 8-year follow-up data. RESULTS: Postoperative histopathological analysis revealed that all patients had grade 1-2 EEC localized to the corpus uteri. Only three patients had deep myometrial invasion (stage IB), but they remained disease-free after 6-9 years of follow-up. The median follow-up time for all patients was 8.7 years. The DFS was 7.6 years, and the OS was 8.6 years. Two patients with stage IA grade 1 EEC experienced relapse and, despite treatment, died of EC. No other EC-related deaths occurred. CONCLUSIONS: The screening algorithm accurately identified low-risk EC patients without compromising survival. Therefore, the algorithm appears to be feasible for selecting patients for surgery in secondary hospitals.


Subject(s)
Algorithms , Endometrial Neoplasms , Magnetic Resonance Imaging , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Middle Aged , Aged , Neoplasm Staging , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/surgery , Adult , Disease-Free Survival , Hysterectomy , Neoplasm Grading , Patient Selection , Risk Factors , Survival Rate , Aged, 80 and over , Retrospective Studies
11.
Appl Immunohistochem Mol Morphol ; 32(5): 222-228, 2024.
Article in English | MEDLINE | ID: mdl-38635473

ABSTRACT

Human epidermal growth factor receptor 2 (HER2) expression has become increasingly helpful in predicting responses to anti-HER2 agents in gynecological cancers. This study retrospectively analyzed HER2 expression in 48 primary ovarian endometrioid carcinomas. HER2 immunohistochemistry was performed using the Ventana platform (Clone 4B5 monoclonal predilute) following the manufacturer's protocol. HER2 expression was equivocal (score 2+) by image analysis in 2 cases (4.17%) based on the breast cancer criteria. Fluorescence in situ hybridization was negative for HER2 amplification in one case (International Federation of Gynecology and Obstetrics, grade 1) and positive in the other (International Federation of Gynecology and Obstetrics, grade 3). Our findings contribute to the growing evidence that HER2 is overexpressed in a small proportion of ovarian endometrioid carcinoma, and thus may serve as a potential therapeutic target in selected cases.


Subject(s)
Carcinoma, Endometrioid , Ovarian Neoplasms , Receptor, ErbB-2 , Humans , Female , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/diagnosis , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/genetics , Middle Aged , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/diagnosis , Aged , Adult , Retrospective Studies , Gene Amplification , Immunohistochemistry , Gene Expression Regulation, Neoplastic , In Situ Hybridization, Fluorescence , Aged, 80 and over
12.
Arch Gynecol Obstet ; 309(6): 2833-2841, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38634898

ABSTRACT

PURPOSE: To assess the real-world prevalence of microsatellite instability (MSI)/mismatch repair (MMR) testing and related tumor status in recurrent/advanced endometrial cancer patients in Europe. METHODS: Data were from two multi-center, retrospective patient chart review studies conducted in the United Kingdom, Germany, Italy, France and Spain: The Endometrial Cancer Health Outcomes-Europe-First-Line (ECHO-EU-1L) study and the ECHO-EU-Second-Line (ECHO-EU-2L) study. ECHO-EU-1L included recurrent/advanced endometrial cancer patients who received first-line systemic therapy between 1/JUN/2016 and 31/MAR/2020 after recurrent/advanced diagnosis. ECHO-EU-2L included patients with recurrent/advanced endometrial cancer who progressed between 1/JUN/2016 and 30/JUN/2019 following prior first-line systemic therapy. Data collected included patient demographics, MSI/MMR tumor testing and results, and clinical/treatment characteristics. RESULTS: ECHO-EU-1L included 242 first-line patients and ECHO-EU-2L included 475 s-line patients. For all patients, median age at recurrent/advanced diagnosis was 69 years, roughly half had endometrioid carcinoma histology and over 75% had Stage IIIB-IV disease at initial diagnosis. The prevalence of MSI/MMR testing in the first-line and second-line cohorts was similar (36.4 and 34.9%, respectively). Among those tested, a majority had non-MSI-high/MMR proficient tumors (80.7 and 74.7% among first- and second-line patients, respectively). About 15% had MSI-high/MMR deficient tumors in both cohorts, and a few patients had discordant results (3.4 and 10.8% among first- and second-line patients, respectively). CONCLUSION: Prior to the approvals of biomarker-directed therapies for recurrent/advanced endometrial cancer patients in Europe, there were low MSI/MMR testing rates for these patients of just over one-third. Given the availability of biomarker-directed therapies, increased MSI/MMR testing may help inform treatment decisions for recurrent/advanced endometrial cancer patients in Europe.


Subject(s)
Endometrial Neoplasms , Microsatellite Instability , Neoplasm Recurrence, Local , Humans , Female , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Aged , Retrospective Studies , Europe/epidemiology , Middle Aged , Prevalence , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/genetics , DNA Mismatch Repair , Neoplasm Staging , Aged, 80 and over , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/epidemiology
13.
Gynecol Oncol ; 183: 103-114, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38593674

ABSTRACT

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.


Subject(s)
Black or African American , Carcinoma, Endometrioid , Disease Progression , Endometrial Neoplasms , White People , Humans , Female , White People/statistics & numerical data , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/therapy , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/ethnology , Carcinoma, Endometrioid/mortality , Endometrial Neoplasms/genetics , Endometrial Neoplasms/therapy , Endometrial Neoplasms/ethnology , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Middle Aged , Black or African American/statistics & numerical data , Aged , Randomized Controlled Trials as Topic , United States/epidemiology , SEER Program , Registries , Clinical Trials, Phase III as Topic , Adult
14.
Cancer Invest ; 42(4): 297-308, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38666471

ABSTRACT

Endometrioid endometrial carcinoma (EEC) stands as a prevalent gynecologic malignancy in developed regions. However, predicting relapse cases remains challenging, necessitating the identification of a novel biomarker for EEC relapse. The assessment of tumor mutational burden (TMB) is pivotal for immunotherapy in EEC patients. However, both whole-exome sequencing (WES) and targeted sequencing encountered application-related difficulties. In light of this, standardized and simplified techniques for TMB measurement are imperative. In this study, we employed WES on 25 EEC patients (12 relapsed cases and 13 non-relapsed cases) who accepted hysterectomy surgery (CHCAMS cohort). We additionally obtained a total of 391 tumor samples with clinicopathological features from TCGA website to broaden the study cohort. In the CHCAMS cohort, the TTN mutant group showed shorter progression-free survival (p < 0.001) and overall survival (p < 0.001) than TTN wild-type group. Additionally, we discovered that the number of TTN mutations per sample was significantly linked with TMB-WES in CHCAMS cohort and TCGA cohort (p < 0.05). And the number of TTN mutations per sample in POLE mutant group was greater than in the POLE wild-type group (p < 0.0001). In conclusion, TTN mutation may serve as a biomarker for EEC prognosis. TTN mutation is also associated with WES-TMB, and could be a simplified TMB measurement technique.


Subject(s)
Carcinoma, Endometrioid , Connectin , Endometrial Neoplasms , Mutation , Humans , Female , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrial Neoplasms/mortality , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/mortality , Middle Aged , Connectin/genetics , Biomarkers, Tumor/genetics , Aged , Prognosis , Exome Sequencing/methods , Adult
15.
J Cancer Res Ther ; 20(1): 232-237, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38554326

ABSTRACT

AIM: We planned this study to assess endometrial cancer (EC) patients who had late metastasis. MATERIALS AND METHODS: This retrospective study constituted a review of the records of patients who were diagnosed with EC and underwent hysterectomy at the Gynecologic Oncology Clinic between 1996 and 2018. Relapses occurring after the first three years following primary treatment of EC are considered late recurrences. Post-relapse survival (PRS) refers to the time to the last follow-up or the patient's death after relapse. RESULTS: Late metastases were identified in 42 patients, 20 (47.6%) of whom had locoregional recurrence and 22 of whom (52.4%) had extrapelvic recurrence. Median disease-free survival (DFS) times were 61 (range: 43-78) and 65 (range: 48-81) months for the groups with locoregional and extrapelvic recurrences, respectively (P = 0.462). The 5-year PRS rate for the patients was 61.1%, with 63.8% having locoregional and 59.4% having extrapelvic late metastasis (P = 0.969). CONCLUSION: Among the patients with late metastases, those with endometrioid type EC were found to have a better prognosis. It has been shown that locoregional or extrapelvic organ recurrence does not significantly affect survival in patients with late relapse. Although our results are not statistically significant for cases of locoregional late metastases, surgical resection increases survival rates.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Female , Humans , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Retrospective Studies
16.
Discov Med ; 36(182): 632-645, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38531804

ABSTRACT

BACKGROUND: Ovarian cancer (OC) accounts for about 4% of female cancers globally. While Ki67-immunopositive (Ki67+) cell density is commonly used to assess proliferation in OC, the two-dimensional (2D) distribution pattern of these cells is poorly understood. This study explores the 2D distribution pattern of Ki67+ cells in primary OC tissues and models the proliferation process to improve our understanding of this hallmark of cancer. METHODS: A total of 100 tissue cores, included in a tissue microarray (TMA) representing 5 clear cell carcinomas, 62 serous carcinomas, 10 mucinous adenocarcinomas, 3 endometrioid adenocarcinomas, 10 lymph node metastases from OC, and 10 samples of adjacent normal ovary tissue, were stained using a standardized immunohistochemical protocol. The computer-aided image analysis system assessed the 2D distribution pattern of Ki67+ proliferating cells, providing the cell number and density, patterns of randomness, and cell-to-cell closeness. Three computer models were created to simulate behavior and responses, aiming to gain insights into the variations in the proliferation process. RESULTS: Significant differences in Ki67+ cell density were found between low- and high-grade serous carcinoma/mucinous adenocarcinomas (p = 0.003 and p = 0.01, respectively). The Nearest Neighbor Index of Ki67+ cells differed significantly between high-grade serous carcinomas and endometrioid adenocarcinomas (p = 0.01), indicating distinct 2D Ki67+ distribution patterns. Proxemics analysis revealed significant differences in Ki67+ cell-to-cell closeness between low- and high-grade serous carcinomas (p = 0.002). Computer models showed varied effects on the overall organization of Ki67+ cells and the ability to preserve the original 2D distribution pattern when altering the location and/or density of Ki67+ cells. CONCLUSIONS: Cell proliferation is a hallmark of OCs. This study provides new evidence that investigating the Ki67+ cell density and 2D distribution pattern can assist in understanding the proliferation status of OCs. Moreover, our computer models suggest that changes in Ki67+ cell density and their location are critical for maintaining the 2D distribution pattern.


Subject(s)
Adenocarcinoma, Mucinous , Carcinoma, Endometrioid , Ovarian Neoplasms , Female , Humans , Carcinoma, Endometrioid/pathology , Ki-67 Antigen , Biomarkers, Tumor/analysis , Ovarian Neoplasms/pathology , Adenocarcinoma, Mucinous/pathology
17.
Medicine (Baltimore) ; 103(11): e37465, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38489719

ABSTRACT

To retrospectively analyze the preoperative and intraoperative influencing factors in predicting the escalation of surgical pathological staging in patients with clinical stage I endometrioid carcinoma. Patients with clinical stage I endometrioid carcinoma at Women's Hospital, School of Medicine, Zhejiang University, between January 2002 and December 2015 were enrolled in this study. Due to preoperative or intraoperative surgical exploration, the patients with one or more preoperative or intraoperative high-risk factors underwent total hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy, totaling 535 cases. The preoperative and intraoperative influencing factors that could lead to the escalation of postoperative surgical pathological staging were further analyzed. 1. There were 535 patients diagnosed with clinical stage I endometrioid carcinoma before surgery, 125 patients were upgraded with postoperative pathological staging, for a rate of 23.36%. 2. Kaplan-Meier survival curve analysis showed that the prognosis in postoperative surgical pathological staging upgraded cases was worse than that in nonupgraded cases. The tumor-free survival and overall survival rates in the 2 groups were significantly different (P < .001). 3. Univariate analysis showed that preoperative degree of myometrial infiltration, intraoperative visual myometrial infiltration depth, massive size of tumor (diameter ≥ 4 cm) and preoperative abnormal serum cancer antigen 125 (CA125) level were associated with the escalation of surgical pathological staging (P < .05). Multivariate analysis indicated that massive size of tumor and preoperative serum abnormal CA125 level were independent predictors of whether postoperative pathological staging would be upgraded (P < .05). 4. The receiver operating characteristic curve drawn with the massive size of tumor and/or the preoperative serum CA125 level abnormality could be used to predict the probability of postoperative pathological upstaging. The results showed that the area from the combination of the 2 factors under the receiver operating characteristic curve was 0.723 (95% confidence interval, 0.672-0.773), suggesting that the combination of massive size of tumor and abnormal preoperative serum CA125 level may serve as an influencing factor for predicting the postoperative pathological staging upgrades. The clinical stage I endometrioid carcinoma patients with massive size of tumor and abnormal preoperative serum CA125 level need to be fully evaluated to ensure appropriate management as soon as possible, since they are more likely to experience postoperative pathological staging upgrades.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Humans , Female , Carcinoma, Endometrioid/surgery , Carcinoma, Endometrioid/pathology , Retrospective Studies , Neoplasm Staging , Endometrial Neoplasms/pathology , Prognosis
20.
Eur J Surg Oncol ; 50(6): 108247, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38522332

ABSTRACT

INTRODUCTION: Endometriosis affects 10% of women of reproductive age. There is evidence for a left lateral predisposition of endometriotic lesions and a 1.9-fold greater risk of ovarian cancer in endometriosis. The aim of this study is to determine whether a left lateral predisposition of ovarian clear-cell carcinoma (CCC) and endometrioid carcinoma (EC) exists. MATERIALS AND METHODS: A retrospective cohort study of all EC and CCC patients in Northern Ireland between March-2011 and June-2018. ANOVA was used to analyse preoperative prediction of stage, chi-squared (χ2) was used to compare left- and right-sided masses. Survival was estimated using Kaplan-Meier and log-rank test. A p-value <0.05 was considered significant. RESULTS: 158 patients were identified (95 EC, 55 CCC, 8 mixed). Mean age was 57.65 years with 69% presenting at stage 1. The mean CA125 was 559 U/mL (p = 0.850) and mean abdominal mass size was 14.12 cm (p = 0.732). The most common presenting symptom was an abdominal mass (37%). Despite 67% of patients having endometriosis on final pathology, only 8.9% had a known history pre-operatively. 51% of tumours were located on the left (p = 0.036). For unilateral tumours this was significant for EC (P = 0.002) but not for CCC (P = 0.555). The 1-, 3- and 5-year overall survival for all types/stages was 85%, 78% and 71% respectively. CONCLUSION: While CCC and EC are associated with endometriosis, only EC exhibits a left lateral predisposition. There is no association between preoperative CA125 or abdominal mass size and stage of disease.


Subject(s)
Adenocarcinoma, Clear Cell , Carcinoma, Endometrioid , Cell Transformation, Neoplastic , Endometriosis , Ovarian Neoplasms , Humans , Female , Endometriosis/pathology , Endometriosis/complications , Carcinoma, Endometrioid/pathology , Ovarian Neoplasms/pathology , Middle Aged , Retrospective Studies , Adenocarcinoma, Clear Cell/pathology , Cell Transformation, Neoplastic/pathology , Adult , CA-125 Antigen/blood , Aged , Neoplasm Staging , Northern Ireland/epidemiology , Survival Rate
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