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Gynecologic Oncology Mar 2020Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival...
OBJECTIVE
Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents.
METHODS
We analyzed gene copy number (n = 191) and DNA sequencing data (n = 184) from primary MOC to evaluate signatures of mismatch repair deficiency and homologous recombination deficiency, and other genetic events. Immunohistochemistry data were collated for ER, CK7, CK20, CDX2, HER2, PAX8 and p16 (n = 117-166).
RESULTS
Molecular aberrations noted in MOC that suggest a match with current targeted therapies include amplification of ERBB2 (26.7%) and BRAF mutation (9%). Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutations (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (HRD) may not be effective in MOC, as only 1/191 had a high HRD score. Mismatch repair deficiency was similarly rare (1/184).
CONCLUSIONS
Although genetically diverse, MOC has several potential therapeutic targets. Importantly, the lack of response to platinum-based therapy observed clinically corresponds to the lack of a genomic signature associated with HRD, and MOC are thus also unlikely to respond to PARP inhibition.
Topics: Adenocarcinoma, Mucinous; Aged; Cohort Studies; DNA Mismatch Repair; Female; Homologous Recombination; Humans; Immunohistochemistry; Mutation; Neoplasm Staging; Ovarian Neoplasms; Receptor, ErbB-2; Receptor, ErbB-3
PubMed: 31902686
DOI: 10.1016/j.ygyno.2019.12.015 -
Modern Pathology : An Official Journal... Jan 2023Similar to PAX8, SOX17 was recently identified as a master transcription factor of ovarian cancer based on RNA sequencing data. We explored SOX17 utility in diagnosing...
Similar to PAX8, SOX17 was recently identified as a master transcription factor of ovarian cancer based on RNA sequencing data. We explored SOX17 utility in diagnosing ovarian tumors and other gynecologic tumors. We systematically evaluated SOX17 expression on tissue microarrays of 398 ovarian tumors of various types, 93 endometrial carcinomas, 80 cervical carcinomas, and 1371 nongynecologic carcinomas, such as those of kidney, thyroid, breast, colon, bladder, liver, bile duct, adrenal gland, pancreas, brain, and lung and malignant melanoma. In addition, we evaluated SOX17 expression in whole tissue sections from 60 gynecologic carcinomas and 10 angiosarcomas. The results demonstrated that SOX17 was highly expressed in most ovarian and endometrial tumors with strong intensity. However, unlike PAX8, it was predominately negative in other tested tumor types, including kidney and thyroid tumors. In particular, SOX17 was highly expressed in the following pathologic subtypes of ovarian tumors: serous carcinoma, clear cell carcinoma, endometrioid carcinoma, and germ cell tumors. SOX17 was mostly negative in mucinous carcinoma and sex cord stromal tumors. In addition, SOX17 was expressed in vascular endothelial cells and was positive in all tested angiosarcomas. In summary, our results demonstrate that SOX17 is a sensitive and specific marker for ovarian nonmucinous carcinomas and endometrial carcinomas. For ovarian germ cell tumors and angiosarcomas, SOX17 demonstrates higher specificity than PAX8, with comparable sensitivity. Furthermore, SOX17 positivity in endothelial cells serves as an internal positive control, making it an excellent marker.
Topics: Humans; Female; Paired Box Transcription Factors; PAX8 Transcription Factor; Endothelial Cells; Hemangiosarcoma; Biomarkers, Tumor; Immunohistochemistry; Ovarian Neoplasms; Genital Neoplasms, Female; Endometrial Neoplasms; Adenocarcinoma, Mucinous; SOXF Transcription Factors
PubMed: 36788073
DOI: 10.1016/j.modpat.2022.100038 -
Cancer Genomics & Proteomics 2020We investigated differences in the clinicopathological and molecular characteristics between gastric-type mucinous carcinoma (GMC) and usual-type endocervical...
BACKGROUND/AIM
We investigated differences in the clinicopathological and molecular characteristics between gastric-type mucinous carcinoma (GMC) and usual-type endocervical adenocarcinoma (UEA).
PATIENTS AND METHODS
We collected the clinicopathological information and performed targeted genomic sequencing analysis.
RESULTS
GMCs exhibited significantly deeper invasion depth, larger horizontal spread, more advanced stage, more frequent distant metastasis, and more frequent parametrial and vaginal extension. Disease-free survival time of GMC patients was significantly shorter than that of UEA patients. GMCs displayed mutant p53 immunostaining pattern, whereas UEAs exhibited p16 block positivity. GMCs harbored mutations in KRAS, TP53, NF1, CDKN2A, STK11, and ARID1A. One GMC exhibited MDM2 amplification. In contrast, UEAs harbored mutations in HRAS, PIK3CA, and BRCA2. Two UEAs were found to have novel TP53 mutations.
CONCLUSION
GMC is associated with more aggressive behavior than UEA. Distinctive p53 and p16 immunostaining patterns enable differential diagnosis. GMC and UEA exhibit genetic heterogeneity with potentially actionable molecular alterations.
Topics: Adenocarcinoma, Mucinous; Adult; Biomarkers, Tumor; Cervix Uteri; Cyclin-Dependent Kinase Inhibitor p16; Diagnosis, Differential; Disease-Free Survival; Female; Humans; Hysterectomy; Middle Aged; Mutation; Neoplasm Invasiveness; Retrospective Studies; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms
PubMed: 32859641
DOI: 10.21873/cgp.20219 -
Journal of Thoracic Oncology : Official... Apr 2022
Topics: Adenocarcinoma, Mucinous; Humans; Lung; Lung Neoplasms
PubMed: 35307110
DOI: 10.1016/j.jtho.2021.07.037 -
Diagnostic Pathology Apr 2023Mucinous carcinoma (MC) is a histological subtype of ovarian cancer that has a worse prognosis at advanced stages than the most prevalent histological subtype,...
BACKGROUND
Mucinous carcinoma (MC) is a histological subtype of ovarian cancer that has a worse prognosis at advanced stages than the most prevalent histological subtype, high-grade serous carcinomas. Invasive patterns have been recognized as prognostic factors for MCs. MCs with infiltrative invasion were more aggressive than those with expansile invasion. MC with an expansile pattern exhibited behavior similar to mucinous borderline tumors (MBT). However, genomic analysis of invasive patterns is insufficient. This study aimed to compare genetic information between groups with MC and infiltrative invasion (Group A) and those with MC with expansile invasion or MBT (Group B).
METHODS
Ten cases each of MC with infiltrative invasion, MC with expansile invasion, and MBT between 2005 and 2020 were identified. Deoxyribonucleic acid (DNA) extraction from formalin-fixed paraffin-embedded tissues was performed, and cases with DNA fragmentation or the possibility of DNA fragmentation were excluded. Mutant base candidates and tumor mutation burden (TMB) values (mutations/megabase) were calculated.
RESULTS
After assessing the quality of purified DNA, seven cases of MC with infiltrative invasion, five cases of MC with expansile invasion, and three cases of MBT were included. More patients in group A experienced recurrence or progression (p < 0.01) and died of disease (p = 0.03). Moreover, the TMB value was statistically higher in group A than in group B (p = 0.049). There were no statistical differences in the incidence of the mutations of KRAS, TP53, and CREBBP. KRAS, TP53, and CREBBP mutations were discovered in 8/15 (53.3%), 6/15 (40.0%), and 5/15 (33.3%) cases, respectively.
CONCLUSIONS
Genetic analysis revealed that Group A had higher TMB than Group B. Therefore, this result might be useful for future treatment.
Topics: Female; Humans; Retrospective Studies; Proto-Oncogene Proteins p21(ras); Neoplasm Staging; Adenocarcinoma, Mucinous; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; DNA
PubMed: 37081552
DOI: 10.1186/s13000-023-01340-w -
Medicine Aug 2021There is a similarity of histological features and survival between ovarian mucinous carcinoma (MC) with expansile invasion and ovarian mucinous borderline tumor (MBT)....
There is a similarity of histological features and survival between ovarian mucinous carcinoma (MC) with expansile invasion and ovarian mucinous borderline tumor (MBT). The aim of this study was to compare the clinical outcomes of MC with expansile invasion with those of MBT based on the 2020 World Health Organization (WHO) criteria.A pathological review was performed on patients with MC, ovarian MBT, and seromucinous borderline tumors that underwent surgery at our hospital between 1984 and 2019. Clinicopathological features were compared retrospectively between MC with expansile invasion and MBT.Among 83 cases of MC, 85 cases of MBT, and 12 cases of seromucinous borderline tumor, 25 MC cases with expansile invasion and 98 MBT cases were included through review. MC cases with expansile invasion were diagnosed with advanced International Federation of Gynecology and Obstetrics (FIGO) stages more frequently (P = .02) than that of MBT cases. In addition, patients with MC with expansile invasion received adjuvant chemotherapy more often (P < .01) than that of patients with MBT. There were no statistically significant differences in recurrence rate (P = .10) between MC with expansile invasion and MBT. Progression-free survival (PFS) was worse in MC cases with expansile invasion than that in MBT cases (P = .01). However, a multivariate analysis for PFS showed that histological subtype, FIGO stage, and adjuvant chemotherapy were not an independent prognostic factor.The prognostic outcome of MC with expansile invasion might mimic those of MBT. These results showed ovarian borderline tumor treatment could be applied to MC treatment.
Topics: Adenocarcinoma, Mucinous; Biopsy; Female; Follow-Up Studies; Humans; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Progression-Free Survival; Retrospective Studies
PubMed: 34397915
DOI: 10.1097/MD.0000000000026895 -
Thoracic Cancer Nov 2020A 77-year-old man who had a persistent productive cough for one month was admitted to our hospital. Chest computed tomography (CT) revealed subpleural nodular opacities,...
A 77-year-old man who had a persistent productive cough for one month was admitted to our hospital. Chest computed tomography (CT) revealed subpleural nodular opacities, irregular pleural thickening with bilateral basal predominance, and a small right pleural effusion. Aspirated fluid was exudative and had the appearance of chylothorax without malignant cells. Surgical lung biopsy specimen showed focal proliferation of neoplastic epithelial cells with lepidic-predominant pattern and abundant mucus in the alveolar spaces, consistent with invasive mucinous adenocarcinoma (IMA). The results of PD-L1 expression and the EGFR, ALK, ROS1, and BRAF mutation status analyzed by next generation sequencer were all negative. IMA should be considered in the differential diagnosis of subpleural micronodular opacities accompanied by pleural effusion (chylothorax) on chest CT. KEY POINTS: Significant findings of the study This case showed subpleural micronodular opacities and chylothorax as unusual chest computed tomography (CT) patterns for invasive mucinous adenocarcinoma (IMA). What this study adds Invasive mucinous adenocarcinoma (IMA) should be considered in the differential diagnosis of subpleural micronodular opacities accompanied by pleural effusion on chest CT.
Topics: Adenocarcinoma, Mucinous; Aged; Chylothorax; Humans; Lung Neoplasms; Male; Tomography, X-Ray Computed
PubMed: 32945109
DOI: 10.1111/1759-7714.13665 -
The Journal of International Medical... Aug 2020As a unique histological subtype of colorectal cancer (CRC), mucinous adenocarcinoma (MC) has a poor prognosis and responds poorly to treatment. Genes and markers...
OBJECTIVE
As a unique histological subtype of colorectal cancer (CRC), mucinous adenocarcinoma (MC) has a poor prognosis and responds poorly to treatment. Genes and markers related to MC have not been reported.
METHODS
To identify biomarkers involved in development of MC compared with other common adenocarcinoma (AC) subtypes, four datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using GEO2R. A protein-protein interaction network was constructed. Functional annotation for DEGs was performed via DAVID, Metascape, and BiNGO. Significant modules and hub genes were identified using Cytoscape, and expression of hub genes and relationships between hub genes and MC were analyzed.
RESULTS
The DEGs were mainly enriched in negative regulation of cell proliferation, bicarbonate transport, response to peptide hormone, cell-cell signaling, cell proliferation, and positive regulation of the canonical Wnt signaling pathway. The Venn diagram revealed eight significant hub genes: , , , , and were highly expressed in MC compared with AC, whereas , , and were expressed at a low level. and might be significant biomarkers for MC.
CONCLUSION
The identified DEGs might help elucidate the pathogenesis of MC, identify potential targets, and improve treatment for CRC.
Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Colorectal Neoplasms; Computational Biology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans
PubMed: 32840168
DOI: 10.1177/0300060520949036 -
Scientific Reports Jun 2022To describe the preoperative nutritional status of Low-grade Appendiceal Mucinous Neoplasms (LAMNs) and identify prognostic factors for survival. Medical records from...
To describe the preoperative nutritional status of Low-grade Appendiceal Mucinous Neoplasms (LAMNs) and identify prognostic factors for survival. Medical records from 165 patients with LAMNs who attended the Aerospace Center Hospital, Beijing, China between January 2017, and December 2018 were retrospectively reviewed. Survival analysis was performed with the Kaplan-Meier method, the log-rank test, and a Cox proportional hazards model. Among 165 patients, 59 (36%) were male and 106 (64%) were female. Patient's median age was 58 years (range 20 to 78 years). Univariate analysis indicated that gender, weight loss, prior surgical score (PSS), red blood cell, albumin, peritoneal cancer index (PCI), completeness of cytoreduction (CCR), and hyperthermic intraperitoneal chemotherapy (HIPEC) were related to prognosis. Multivariate analysis showed that PSS, CCR and HIPEC were independent predictors of prognosis. The preoperative nutritional status of patients plays an important role in predicting prognosis. Patients can benefit from a complete cytoreductive surgery (CCRS) and HIPEC in an experienced institution for the first medical treatment.
Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Combined Modality Therapy; Female; Humans; Hyperthermia, Induced; Male; Middle Aged; Nutritional Status; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 35739171
DOI: 10.1038/s41598-022-14765-y -
Korean Journal of Radiology Mar 2022To compare pneumonic-type invasive mucinous adenocarcinoma (pIMA) confined to a single lobe with clinical T2, T3, and T4 stage lung cancer without pathological node...
OBJECTIVE
To compare pneumonic-type invasive mucinous adenocarcinoma (pIMA) confined to a single lobe with clinical T2, T3, and T4 stage lung cancer without pathological node metastasis regarding survival after curative surgery and to identify prognostic factors for pIMA.
MATERIALS AND METHODS
From January 2010 to December 2017, 41 patients (15 male; mean age ± standard deviation, 66.0 ± 9.9 years) who had pIMA confined to a single lobe on computed tomography (CT) and underwent curative surgery were identified in two tertiary hospitals. Three hundred and thirteen patients (222 male; 66.3 ± 9.4 years) who had non-small cell lung cancer (NSCLC) without pathological node metastasis and underwent curative surgery in one participating institution formed a reference group. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Cox proportional hazard regression analysis was performed to identify factors associated with the survival of patients with pIMA.
RESULTS
The 5-year RFS and OS rates in patients with pIMA were 33.1% and 56.0%, respectively, compared with 74.3% and 91%, 64.3% and 71.8%, and 46.9% and 49.5% for patients with clinical stage T2, T3, and T4 NSCLC in the reference group, respectively. The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 NSCLC and significantly worse than that of patients with clinical stage T3 NSCLC ( = 0.012). The differences in OS between patients with pIMA and those with clinical stage T3 or T4 NSCLC were not significant ( = 0.11 and = 0.37, respectively). In patients with pIMA, the presence of separate nodules was a significant factor associated with poor RFS and OS {unadjusted hazard ratio (HR), 4.66 (95% confidence interval [CI], 1.95-11.11), < 0.001 for RFS; adjusted HR, 4.53 (95% CI, 1.59-12.89), = 0.005 for OS}.
CONCLUSION
The RFS of patients with pIMA was comparable to that of patients with clinical stage T4 lung cancer. Separate nodules on CT were associated with poor RFS and OS in patients with pIMA.
Topics: Adenocarcinoma of Lung; Adenocarcinoma, Mucinous; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Potassium Iodide; Prognosis; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 35213098
DOI: 10.3348/kjr.2021.0465