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International Journal of Gynecological... Sep 2023Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly...
Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.
Topics: Humans; Female; Consensus; Quality of Life; Peritoneal Neoplasms; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Papillary; Cystadenocarcinoma, Serous; Ovarian Neoplasms
PubMed: 37591609
DOI: 10.1136/ijgc-2023-004610 -
Neurological Research Mar 2024Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the...
BACKGROUND
Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C (A3C) has been identified as a cancer molecular biomarker in the past decade. However, the practical role of A3C in lower-grade gliomas (LGGs) in improving the clinical outcome remains unclear. This study aims to discuss the function of A3C in immunotherapy in LGGs.
METHODS
The RNA-Sequencing (RNA-seq) and corresponding clinical data were extracted from UCSC Xena and the results were verified in the Chinese Glioma Genome Atlas (CGGA). Weighted gene co-expression network analysis (WGCNA) was used for screening A3C-related genes. Comprehensive bioinformation analyses were performed and multiple levels of expression, survival rate, and biological functions were assessed to explore the functions of A3C.
RESULTS
A3C expression was significantly higher in LGGs than in normal tissues but lower than in glioblastoma (GBM), indicating its role as an independent prognosis predictor for LGGs. Twenty-eight A3C-related genes were found with WGCNA for unsupervised clustering analysis and three modification patterns with different outcomes and immune cell infiltration were identified. A3C and the A3C score were also correlated with immune cell infiltration and the expression of immune checkpoints. In addition, the A3C score was correlated with increased sensitivity to chemotherapy. Single-cell RNA (scRNA) analysis indicated that A3C most probably expresses on immune cells, such as T cells, B cells and macrophage.
CONCLUSIONS
A3C is an immune-related prognostic biomarker in LGGs. Developing drugs to block A3C could enhance the efficiency of immunotherapy and improve disease survival. A3C: Apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) type 3C; LGGs: lower-grade gliomas; CGGA: Chinese Glioma Genome Atlas; WGCNA: Weighted gene co-expression network analysis; scRNA: Single-cell RNA; HGG: higher-grade glioma; OS: overall survival; TME: tumor microenvironment; KM: Kaplan-Meier; PFI: progression-free interval; IDH: isocitrate dehydrogenase; ROC: receiver operating characteristic; GS: gene significance; MM: module membership; TIMER: Tumor IMmune Estimation Resource; GSVA: gene set variation analysis; ssGSEA: single-sample gene-set enrichment analysis; PCA: principal component analysis; AUC: area under ROC curve; HAVCR2: hepatitis A virus cellular receptor 2; PDCD1: programmed cell death 1; PDCD1LG2: PDCD1 ligand 2; PTPRC: protein tyrosine phosphatase receptor type C; ACC: Adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma;BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOLCholangiocarcinoma; COADColon adenocarcinoma; DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney Chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute Myeloid Leukemia; LGG: Brain Lower Grade Glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and Paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach adenocarcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCS: Uterine Carcinosarcoma; UVM: Uveal Melanoma.
Topics: Male; Female; Humans; Melanoma; Adenocarcinoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Uterine Cervical Neoplasms; Pancreatic Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Glioma; Glioblastoma; Biomarkers; Peptides; RNA; RNA, Messenger; Apolipoproteins; Prognosis; Cytidine Deaminase
PubMed: 38007705
DOI: 10.1080/01616412.2023.2287340 -
Gynecologic Oncology Jul 2023Low-grade serous ovarian carcinoma (LGSOC) is a distinct, rare, ovarian cancer type characterised by younger patient age and intrinsic chemoresistance. Understanding the...
OBJECTIVES
Low-grade serous ovarian carcinoma (LGSOC) is a distinct, rare, ovarian cancer type characterised by younger patient age and intrinsic chemoresistance. Understanding the molecular landscape is crucial for optimising targeted therapy.
METHODS
Genomic data from whole exome sequencing of tumour tissue was analysed in a LGSOC cohort with detailed clinical annotation.
RESULTS
63 cases were analysed and three subgroups identified based on single nucleotide variants: canonical MAPK mutant (cMAPKm: 52%, KRAS/BRAF/NRAS), MAPK-associated gene mutation (MAPK-assoc: 27%) and MAPK wild-type (MAPKwt: 21%). NOTCH pathway disruption occurred across all subgroups. Tumour mutational burden (TMB), mutational signatures and recurrent copy number (CN) changes varied across the cohort with co-occurrence of chromosome 1p loss and 1q gain (CN Chr1pq) a recurrent feature. Low TMB and CN Chr1pq were associated with inferior disease-specific survival (HR 6.43; p < 0.001 and HR 3.29, p = 0.011 respectively). Stepwise genomic classification in relation to outcome resulted in four groups (TMB low; CN Chr1pq; MAPKwt/MAPKassoc; cMAPKm). 5 year disease-specific survival was 46%, 55%, 79% and 100% respectively for these groups. The two most favourable genomic subgroups were enriched for the SBS10b mutational signature, particularly the cMAPKm subgroup.
CONCLUSIONS
LGSOC comprises multiple genomic subgroups with distinct clinical and molecular features. Chr1pq CN arm disruption and TMB represent promising methods to identify individuals with poorer prognosis. Further investigation of the molecular basis for these observations is required. MAPKwt cases represent around a fifth of patients. NOTCH inhibitors represent a candidate therapeutic strategy worthy of exploration across these cases.
Topics: Female; Humans; Exome Sequencing; Ovarian Neoplasms; Cystadenocarcinoma, Serous; Mutation; Biomarkers, Tumor; Cystadenocarcinoma, Papillary; Genomics
PubMed: 37207500
DOI: 10.1016/j.ygyno.2023.04.011 -
International Journal of Surgical... Dec 2023With <40 case reports published in the English literature, mucinous cystadenocarcinoma of the breast is quite rare compared to its counterparts in the ovary, pancreas,...
With <40 case reports published in the English literature, mucinous cystadenocarcinoma of the breast is quite rare compared to its counterparts in the ovary, pancreas, and appendix. The purpose of this case report is to enrich scientific data by sharing the clinicopathological features of this new and extremely rare entity and present possible difficulties encountered in the biopsy materials. A 34-year-old female patient presented with the complaint of white discharge from her left nipple lasting 8 months. Physical and radiological examination of the patient revealed a mass in the lower quadrant of the left breast and tru-cut biopsy was performed. The diagnosis of invasive breast carcinoma of no special type was reported. After neoadjuvant chemotherapy, left subcutaneous mastectomy and left sentinel lymph node biopsy were performed. Microscopic evaluation of the mastectomy material revealed a tumor consisting of stratified columnar cells with basally located nuclei and intracytoplasmic mucin, showing papillary structures and tufting toward the lumen. Peripheral myoepithelial cells were not identified with p63 and calponin immunohistochemistry. The diagnosis of mucinous cystadenocarcinoma was given through histomorphological and immunohistochemical evaluations. Clarifying unknown points about this rare malignancy of the breast and understanding the tumor biology is possible through evaluation of case reports. For this purpose, our case of primary mucinous cystadenocarcinoma is presented and its clinicopathological features are briefly discussed.
PubMed: 38073094
DOI: 10.1177/10668969231214805 -
Gynecologic Oncology May 2024Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy in the United States, and biomarkers of patient outcomes are limited. Data using...
OBJECTIVE
Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy in the United States, and biomarkers of patient outcomes are limited. Data using immunohistochemical (IHC) analysis are mixed regarding whether and which tumor infiltrating lymphocytes (TILs) impact survival, and IHC does not adequately quantify rare cell populations, including CD137+ (4-1BB) tumor-reactive TILs. Our study investigates if a higher percentage of CD3+ CD137+ TILs is associated with improved overall survival (OS) in OC.
METHODS
Flow cytometry was performed on viably banked OC digests. Chart review and statistical analysis were performed. Forty-seven patients were included, 40 of whom were diagnosed with high-grade serous ovarian carcinoma (HGSOC), papillary serous carcinoma, or undifferentiated histology.
RESULTS
A high percentage of CD3+ CD137+ TILs correlated with improved OS (n = 40, r = 0.48, P = 0.0016). Subjects were divided into CD3+ CD137+ TIL high and low groups by the median. Subjects with high CD3+CD137+ TIL frequencies (>9.6%) had longer OS (Wilcoxon rank-sum test; P = 0.0032) and improved OS (logrank test; P = 0.007). Differences in CD3+ or CD3+ CD8+ TILs did not impact survival. CD3+ CD137+ TILs were predictive of OS regardless of germline mutation or debulking status. Analysis of subgroups including late stage HGSOC and late stage HGSOC with primary optimal cytoreduction indicated CD3+ CD137+ TILs correlated with improved OS after adjusting for age and PARP inhibitor use (P = 0.034 and P = 0.016, respectively).
CONCLUSIONS
Prevalence of CD3+ CD137+ TILs in digested OC specimens is associated with improved OS, while general TIL markers are not. CD137 has the potential to be a novel biomarker for survival in OC.
Topics: Humans; Female; Lymphocytes, Tumor-Infiltrating; Tumor Necrosis Factor Receptor Superfamily, Member 9; Ovarian Neoplasms; Middle Aged; Aged; CD3 Complex; Adult; Cystadenocarcinoma, Serous; Aged, 80 and over
PubMed: 38290413
DOI: 10.1016/j.ygyno.2024.01.029 -
Cancer Cytopathology Jul 2023SOX17 (SRY-box transcription factor 17) was recently identified as a highly sensitive and specific marker for ovarian and endometrial carcinomas in surgical specimens....
BACKGROUND
SOX17 (SRY-box transcription factor 17) was recently identified as a highly sensitive and specific marker for ovarian and endometrial carcinomas in surgical specimens. In this study, validation of the utility of SOX17 immunohistochemistry (IHC) in diagnosing metastatic gynecologic carcinomas in cytology specimens was sought.
METHODS
The study cohort included 84 cases of metastatic carcinomas that included 29 metastatic gynecologic carcinomas (24 ovarian high-grade serous carcinomas, two endometrial serous carcinomas, one low-grade serous carcinoma, one ovarian clear cell carcinoma, and one endometrial endometrioid carcinoma) and 55 cases of metastatic nongynecologic carcinomas (10 clear cell renal cell carcinomas, 10 papillary thyroid carcinomas, 11 gastrointestinal adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, and four urothelial carcinomas). Cytology specimen types included peritoneal fluid (n = 44), pleural fluid (n = 25), and fine-needle aspiration (n = 15). SOX17 IHC was performed on the cell block sections. The intensity of staining and percent positivity of the tumor cells were evaluated.
RESULTS
SOX17 was highly expressed in all tested metastatic gynecologic carcinomas with diffuse and strong nuclear expression (29 of 29; 100%). SOX17 was negative in other metastatic nongynecologic carcinomas (54 of 55; 98.18%) except for one papillary thyroid carcinoma that showed low positivity (<10%).
CONCLUSIONS
SOX17 is a highly sensitive (100%) and specific (98.2%) marker for the differential diagnosis of metastatic gynecologic carcinomas in cytology specimens. Therefore, SOX17 IHC should be included in the workup of differential diagnosis of metastatic gynecologic carcinomas in cytology specimens.
Topics: Humans; Female; Biomarkers, Tumor; Endometrial Neoplasms; Adenocarcinoma; Carcinoma; Cystadenocarcinoma, Serous; SOXF Transcription Factors
PubMed: 37195085
DOI: 10.1002/cncy.22708 -
Gynecologic Oncology Aug 2023To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of...
OBJECTIVE
To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery.
METHODS
We identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004-December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control.
RESULTS
We observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6-8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07-1.24), and stage IV disease (RR 2.66; 95% CI 2.31-3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65-0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08-1.42).
CONCLUSION
NACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures.
Topics: Humans; Female; United States; Ovarian Neoplasms; Neoadjuvant Therapy; Chemotherapy, Adjuvant; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Peritoneal Neoplasms; Cystadenocarcinoma, Papillary; Cytoreduction Surgical Procedures; Neoplasm Staging; Retrospective Studies
PubMed: 37327540
DOI: 10.1016/j.ygyno.2023.06.001 -
Diagnostic Cytopathology Jun 2024Primary mucinous cystadenocarcinoma (MCA) of the breast is a rare variant of breast carcinoma. A 68-year-old female patient presented to the general surgery clinic with...
Primary mucinous cystadenocarcinoma (MCA) of the breast is a rare variant of breast carcinoma. A 68-year-old female patient presented to the general surgery clinic with pain and swelling in the right breast. A mass was detected in the upper outer quadrant, and a fine-needle aspiration biopsy was performed. The May-Grünwald Giemsa stained slides showed aggregates of mucin-rich pleomorphic cells with large nuclei in a mucinous background containing discohesive single cells. The Papanicolaou stain revealed a papillary structure composed of malignant epithelial cells in a necrotic background. A modified radical mastectomy was performed, and upon gross examination, two tumors were discovered in the central and upper outer quadrants. The first tumor, located centrally, was identified as invasive lobular breast carcinoma. The second tumor was an MCA with cytokeratin 7(+) and cytokeratin 20(-), and was determined to be the primary MCA of the breast based on clinical and radiological information. Immunohistochemistry revealed that the tumor cells were negative for estrogen receptor and progesterone receptor, and HER2 was 2+. Fluorescence in situ hybridization analysis detected HER2 gene amplification. During the 72-month follow-up, there were no findings compatible with recurrence or new metastasis. Although primary MCA is rare, it causes differential diagnosis problems and has different biological behaviors.
PubMed: 38837688
DOI: 10.1002/dc.25364 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Jan 2024To investigate the expression level of tetratricopeptide repeat protein 9A in tumors and its association with the patients' prognosis and immune infiltration.
OBJECTIVE
To investigate the expression level of tetratricopeptide repeat protein 9A in tumors and its association with the patients' prognosis and immune infiltration.
METHODS
TTC9A expression in different tumor tissues and its association with prognosis, DNA methylation, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed based on data from TCGA and GTEx. TIMER and xCell were used to analyze the relationship between TTC9A expression and immune infiltration. Western blotting and RT-qPCR were used to detect the expression of TTC9A in 4 types of cancer cell lines.
RESULTS
TTC9A expressions were significantly increased in many tumors and down-regulated in a few cancer types ( < 0.05). Western blotting and RT-qPCR showed that TTC9A expressions were elevated in lung, colon and liver cancer cells but decreased in bladder cancer cells. In head and neck squamous cell carcinoma, renal clear cell carcinoma, renal papillary cell carcinoma, low-grade glioma, malignant mesothelioma, and endometrial carcinoma tumors, a high expression of TTC9A was strongly correlated with better overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) ( < 0.05), but was correlated with worse OS, DSS, and PFI in lung adenocarcinoma, pancreatic adenocarcinoma, adrenal carcinoma, and rectal adenocarcinoma ( < 0.05). TTC9A hypermethylation was associated with a more favorable prognosis of glioblastoma multiforme, low- grade glioma, uveal melanoma, and ovarian plasmacytoid cystadenocarcinoma ( < 0.05) but with poor prognosis of squamous cell carcinoma of the uterine cervix and intracervical adenocarcinoma, squamous cell carcinoma of head and neck, squamous cell carcinoma of the lungs, adrenal carcinoma, and endometrial carcinoma ( < 0.05). In most of the cancer types, TTC9A was significantly correlated with the level of immune cell infiltration ( < 0.05).
CONCLUSION
TTC9A can be used as a prognostic marker for a variety of cancers and is strongly associated with TBM, MSI and immune cell infiltration.
Topics: Female; Humans; Adenocarcinoma; Carcinoma, Renal Cell; Carcinoma, Squamous Cell; Endometrial Neoplasms; Glioma; Kidney Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Prognosis; Tumor Microenvironment
PubMed: 38293978
DOI: 10.12122/j.issn.1673-4254.2024.01.09 -
Urology Case Reports Nov 2023Prostate papillary and cribriform ductal prostatic adenocarcinoma is a rare malignancy infrequently reported in the literature. We describe a case of rectally invasive...
Prostate papillary and cribriform ductal prostatic adenocarcinoma is a rare malignancy infrequently reported in the literature. We describe a case of rectally invasive prostate cystic adenocarcinoma and surgical extirpative management not requiring fecal or urinary diversion.
PubMed: 37942212
DOI: 10.1016/j.eucr.2023.102597