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International Journal of Gynaecology... Aug 2023Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009....
INTRODUCTION
Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies.
METHODS
The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system.
RESULTS
Based on the existing evidence, the substages were defined as follows: Stage I (IA1): non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. Stage II (IIA): non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. Stage III (IIIA): differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. Stage IV (IVA): locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification (POLEmut, MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or POLEmut status in Stages I and II, this results in upstaging or downstaging of the disease (IICm or IAm ).
SUMMARY
The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data.
Topics: Female; Humans; Peritoneal Neoplasms; Neoplasm Staging; Endometrial Neoplasms; Prognosis; Carcinoma, Endometrioid; Retrospective Studies
PubMed: 37337978
DOI: 10.1002/ijgo.14923 -
Journal of Gynecologic Oncology Sep 2023Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009....
INTRODUCTION
Many advances in the understanding of the pathologic and molecular features of endometrial cancer have occurred since the FIGO staging was last updated in 2009. Substantially more outcome and biological behavior data are now available regarding the several histological types. Molecular and genetic findings have accelerated since the publication of The Cancer Genome Atlas (TCGA) data and provide improved clarity on the diverse biological nature of this collection of endometrial cancers and their differing prognostic outcomes. The goals of the new staging system are to better define these prognostic groups and create substages that indicate more appropriate surgical, radiation, and systemic therapies.
METHODS
The FIGO Women's Cancer Committee appointed a Subcommittee on Endometrial Cancer Staging in October 2021, represented by the authors. Since then, the committee members have met frequently and reviewed new and established evidence on the treatment, prognosis, and survival of endometrial cancer. Based on these data, opportunities for improvements in the categorization and stratification of these factors were identified in each of the four stages. Data and analyses from the molecular and histological classifications performed and published in the recently developed ESGO/ESTRO/ESP guidelines were used as a template for adding the new subclassifications to the proposed molecular and histological staging system.
RESULTS
Based on the existing evidence, the substages were defined as follows: non-aggressive histological type of endometrial carcinoma limited to a polyp or confined to the endometrium; (IA2) non-aggressive histological types of endometrium involving less than 50% of the myometrium with no or focal lymphovascular space invasion (LVSI) as defined by WHO criteria; (IA3) low-grade endometrioid carcinomas limited to the uterus with simultaneous low-grade endometrioid ovarian involvement; (IB) non-aggressive histological types involving 50% or more of the myometrium with no LVSI or focal LVSI; (IC) aggressive histological types, i.e. serous, high-grade endometrioid, clear cell, carcinosarcomas, undifferentiated, mixed, and other unusual types without any myometrial invasion. non-aggressive histological types that infiltrate the cervical stroma; (IIB) non-aggressive histological types that have substantial LVSI; or (IIC) aggressive histological types with any myometrial invasion. differentiating between adnexal versus uterine serosa infiltration; (IIIB) infiltration of vagina/parametria and pelvic peritoneal metastasis; and (IIIC) refinements for lymph node metastasis to pelvic and para-aortic lymph nodes, including micrometastasis and macrometastasis. locally advanced disease infiltrating the bladder or rectal mucosa; (IVB) extrapelvic peritoneal metastasis; and (IVC) distant metastasis. The performance of complete molecular classification (, MMRd, NSMP, p53abn) is encouraged in all endometrial cancers. If the molecular subtype is known, this is recorded in the FIGO stage by the addition of "m" for molecular classification, and a subscript indicating the specific molecular subtype. When molecular classification reveals p53abn or status in Stages I and II, this results in upstaging or downstaging of the disease (IICm or IAm).
SUMMARY
The updated 2023 staging of endometrial cancer includes the various histological types, tumor patterns, and molecular classification to better reflect the improved understanding of the complex nature of the several types of endometrial carcinoma and their underlying biologic behavior. The changes incorporated in the 2023 staging system should provide a more evidence-based context for treatment recommendations and for the more refined future collection of outcome and survival data.
Topics: Female; Humans; Peritoneal Neoplasms; Endometrial Neoplasms; Endometrium; Uterus; Carcinoma, Endometrioid
PubMed: 37593813
DOI: 10.3802/jgo.2023.34.e85 -
Seminars in Cancer Biology Oct 2023Olive oil (OO) is the main source of added fat in the Mediterranean diet (MD). It is a mix of bioactive compounds, including monounsaturated fatty acids, phytosterols,... (Review)
Review
Olive oil (OO) is the main source of added fat in the Mediterranean diet (MD). It is a mix of bioactive compounds, including monounsaturated fatty acids, phytosterols, simple phenols, secoiridoids, flavonoids, and terpenoids. There is a growing body of evidence that MD and OO improve obesity-related factors. In addition, obesity has been associated with an increased risk for several cancers: endometrial, oesophageal adenocarcinoma, renal, pancreatic, hepatocellular, gastric cardia, meningioma, multiple myeloma, colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancer. However, the epidemiological evidence linking MD and OO with these obesity-related cancers, and their potential mechanisms of action, especially those involving the gut microbiota, are not clearly described or understood. The goals of this review are 1) to update the current epidemiological knowledge on the associations between MD and OO consumption and obesity-related cancers, 2) to identify the gut microbiota mechanisms involved in obesity-related cancers, and 3) to report the effects of MD and OO on these mechanisms.
Topics: Humans; Olive Oil; Diet, Mediterranean; Obesity; Neoplasms; Gastrointestinal Microbiome
PubMed: 37543179
DOI: 10.1016/j.semcancer.2023.08.001 -
Journal of the National Cancer Institute Aug 2023Intratumoral microbes may have multifunctional roles in carcinogenesis. Microsatellite instability (MSI) is associated with higher tumor immunity and mutational burden....
Intratumoral microbes may have multifunctional roles in carcinogenesis. Microsatellite instability (MSI) is associated with higher tumor immunity and mutational burden. Using whole transcriptome and whole genome sequencing microbial abundance data, we investigated associations of intratumoral microbes with MSI, survival, and MSI-relevant tumor molecular characteristics across multiple cancer types including colorectal cancer (CRC), stomach adenocarcinoma, and endometrial carcinoma. Among 451 CRC patients, our key finding was strong associations of multiple CRC-associated genera, including Dialister and Casatella, with MSI. Dialister and Casatella abundance was associated with improved overall survival (hazard ratiomortality = 0.56, 95% confidence interval = 0.34 to 0.92, and hazard ratiomortality = 0.44, 95% confidence interval = 0.27 to 0.72), respectively, comparing higher relative to lower quantiles. Multiple intratumor microbes were associated with immune genes and tumor mutational burden. Diversity of oral cavity-originating microbes was also associated with MSI among CRC and stomach adenocarcinoma patients. Overall, our findings suggest the intratumor microbiota may differ by MSI status and play a role in influencing the tumor microenvironment.
Topics: Humans; Microsatellite Instability; Colorectal Neoplasms; Stomach Neoplasms; Adenocarcinoma; Tumor Microenvironment
PubMed: 37192013
DOI: 10.1093/jnci/djad083 -
Journal of Oncology Pharmacy Practice :... Sep 2023The purpose of this article is to review the pharmacology, safety, evidence for current use, and potential futures uses for combination therapy with pembrolizumab and... (Review)
Review
OBJECTIVE
The purpose of this article is to review the pharmacology, safety, evidence for current use, and potential futures uses for combination therapy with pembrolizumab and lenvatinib.
DATA SOURCES
A literature review was carried out through PubMed to identify ongoing trials evaluating use, efficacy, and safety of combination pembrolizumab and lenvatinib. NCCN guidelines were utilized to identify current approved uses in therapy and medication package inserts were used to identify pharmacology and preparation requirements.
DATA SUMMARY
A total of five completed clinical trials and two ongoing trials were evaluated for use and safety of pembrolizumab with lenvatinib. Data suggests that combination therapy with pembrolizumab and lenvatinib can be used first line for clear cell renal carcinoma in patients with favorable risk or intermediate/poor risk and in endometrial carcinoma as a preferred second-line regimen for recurrent or metastatic disease for biomarker-directed systemic therapy in non-MSI-H/non-dMMR tumors. This combination may have potential for use in unresectable hepatocellular carcinoma and gastric cancer.
CONCLUSIONS
Use of non-chemotherapy containing regimens spare patients from extended durations of myelosuppression and reduce the risk of infection. Additionally, pembrolizumab with lenvatinib demonstrates efficacy as first line treatment in clear cell renal carcinoma, second line in endometrial carcinoma, and several potential uses on the horizon.
Topics: Female; Humans; Carcinoma, Renal Cell; Antineoplastic Combined Chemotherapy Protocols; Phenylurea Compounds; Quinolines; Endometrial Neoplasms; Kidney Neoplasms
PubMed: 37231712
DOI: 10.1177/10781552231178461 -
Scientific Reports Oct 2023Cuproptosis is a unique type of cell death that may influence tumour formation by targeting lipoylated tricarboxylic acid cycle proteins. Solute carrier family 31 member...
Cuproptosis is a unique type of cell death that may influence tumour formation by targeting lipoylated tricarboxylic acid cycle proteins. Solute carrier family 31 member 1 (SLC31A1), an important copper transporter, influences dietary copper absorption in the cell membrane. However, various SLC31A1 properties in pan-cancer profiles remain unknown. This study investigated the role of SLC31A1 in human malignancies and analysed its prognostic value. Raw data were obtained from The Cancer Genome Atlas database and processed using numerous internet databases, including UALCAN, GEPIA, cBioPortal, TIMER2.0, and Human Protein Atlas. SLC31A1 expression was found to be elevated in cervical, endometrial, and breast cancers compared to that in normal tissues, but reduced in clear cell renal cell carcinoma, liver hepatocellular carcinoma, and lung adenocarcinoma. Furthermore, SLC31A1 expression was strongly associated with overall survival and disease-free survival in several cancers. SLC31A1 gene mutations and methylations were identified in 33 cancers. SLC31A1 expression was positively correlated with immune cells in immune infiltration data. Single-cell sequencing revealed that SLC31A1 may play key roles in DNA repair, DNA damage, and proliferation. These findings may lead to better understanding of SLC31A1 in pan-cancer profiles and suggest that SLC31A1 could be a viable predictive biomarker, particularly in gynaecological cancers.
Topics: Humans; Carcinoma, Hepatocellular; Copper; Copper Transporter 1; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Prognosis; Apoptosis
PubMed: 37853210
DOI: 10.1038/s41598-023-44681-8 -
Medicina (Kaunas, Lithuania) Mar 2024: Endometrial carcinoma is one of the most common gynecological cancers, and benign lesions such as endometrial hyperplasia, polyps, adenomyosis and leiomyomas should be...
: Endometrial carcinoma is one of the most common gynecological cancers, and benign lesions such as endometrial hyperplasia, polyps, adenomyosis and leiomyomas should be included in the differential diagnosis. Magnetic resonance imaging has an important role in evaluating endometrial cancer and assessing the depth of myometrial invasion, and it closely correlates with the prognosis of the patient. The purpose of this study is to evaluate the MRI semiology of the endometrial carcinomas that mimic benign lesions, the main factors that may affect the correct diagnosis and the feasibility of magnetic resonance imaging to evaluate the depth of the myometrial invasion of endometrial cancer. : This is a retrospective analysis of 45 patients that underwent MRI examinations and the lesions were pathologically diagnosed as endometrial carcinoma after surgical resection. This study evaluated the staging accuracy of T2-weighted imaging, diffusion-weighted imaging (DWI), ADC mapping and T1-weighted imaging with fat saturation before and after gadolinium injection. : In 36 of the 45 cases, the MRI of the lesion showed the characteristics of endometrial cancer and the diagnosis was certain. Nine lesions (20%) were described as unequivocal and had unspecific MR appearance. In eight of the nine cases (89%), the histopathologic report revealed the presence of leiomyomas and two of these cases (22%) were also associated with adenomyosis. The cause of underestimation in these patients was coexisting lesions exhibiting heterogenous intensity and contrast enhancement, which made it difficult to detect the margins of the lesions. The depth of the myometrial invasion was underestimated in nine cases and overestimated in three cases. The staging accuracy with MRI was 74%. There was a significant correlation between MR imaging and histopathologic finding in the assessment of myometrial invasion ( < 0.001). Cervical extension was noted in eight cases (18%), but was missed on MR imaging in two patients and overstaged in none. Six of them were associated with myometrial invasion in more than 50% of the thickness. There was a significant correlation between MR imaging and histopathologic finding in the assessment of cervical extension ( < 0.001). : Our data confirm the high accuracy of MRI in the diagnosis and local staging of endometrial carcinoma. The information provided by MRI has an important role in planning the treatment and the prognosis of the patients.
Topics: Female; Humans; Adenomyosis; Retrospective Studies; Neoplasm Invasiveness; Magnetic Resonance Imaging; Uterine Neoplasms; Endometrial Neoplasms; Neoplasm Staging; Leiomyoma; Adenocarcinoma; Sensitivity and Specificity
PubMed: 38541238
DOI: 10.3390/medicina60030512 -
Heliyon Jun 2023The alanine-serine-cysteine transporter 2, ASCT2 (solute carrier family 1 member 5, SLC1A5), is a major transporter of the amino acid, glutamine. Although SLC1A5 has...
BACKGROUND
The alanine-serine-cysteine transporter 2, ASCT2 (solute carrier family 1 member 5, SLC1A5), is a major transporter of the amino acid, glutamine. Although SLC1A5 has been reported to be associated with some types of cancer, less pan-cancer analysis, which would give a comprehensive understanding of SLC1A5 across human cancers, has been carried out.
METHODS
We used the TCGA and GEO databases to investigate the oncogenic role of SLC1A5. We examined gene and protein expression, survival, genetic mutations, protein phosphorylation, immunocyte infiltration and the related genes correlated pathways. In HCT116 cells, SLC1A5 was silenced by siRNAs and the mRNA and protein was checked by Q-PCR and WB, respectively and the cellular function was assessed by CCK8, cell cycle and apoptosis.
RESULTS
We found that SLC1A5 was over-expressed in multiple types of cancer and that elevated expression of SLC1A5 was associated with poor survival in many cancers. The missense mutation of R330 H/C was associated with poor survival, especially in uterine carcinosarcoma. Furthermore, we found enhanced phosphorylation of S503 in uterine corpus endometrial carcinoma and lung adenocarcinoma. In addition, elevated SLC1A5 expression was associated with immune cell infiltration in many cancers. KEGG and GO analysis showed that SLC1A5 and its related genes were involved in central carbon metabolism in cancer, due to their amino acid transport activity. The cellular function indicated that SLC1A5 may influence the cell proliferation by affecting DNA synthesis.
CONCLUSIONS
Our findings highlighted the important role of SLC1A5 in tumorigenesis and provided insights into potential cancer treatment strategies.
PubMed: 37408893
DOI: 10.1016/j.heliyon.2023.e17598