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Journal of Ovarian Research Oct 2021Mixed cell ovarian adenocarcinoma (MCOA) is a malignant gynecologic tumor consisting of serous, mucous, and papillary tumor cells. However, the clinical features and...
BACKGROUND
Mixed cell ovarian adenocarcinoma (MCOA) is a malignant gynecologic tumor consisting of serous, mucous, and papillary tumor cells. However, the clinical features and prognosis of MCOA patients are unclear.
METHODS
In this study, univariate and multivariate Cox proportional risk models were performed to identify independent prognostic factors. The Kaplan-Meier method was used to assess the relationship between clinical characteristics and patient survival. Finally, a nomogram was constructed and validated to predict patient survival time, and the C-index was used to evaluate the efficacy of the nomogram.
RESULTS
A total of 2,818 patients diagnosed with MCOA were identified, and the 5-year survival rate was 62%. Univariate and multivariate Cox models suggested that age (HR=1.28, 95% CI[1.15,1.44]), grade (HR=1.26, 95% CI[1.12,1.41]), SEER stage (HR=1.63, 95% CI[1.25,2.13]) and AJCC (American Joint Committee on Cancer) stage (HR=1.59, 95% CI[1.36,1.86]) were independent prognostic factors for MCOA patients. After propensity score matching for age, grade, SEER stage, and AJCC stage, the 5-year survival rate was 69.7% for ovarian serous cystadenocarcinoma and 62.9% for ovarian papillary serous cystadenocarcinoma. These results mean that serous adenocarcinoma had the best prognosis of the three pathologic types of ovarian carcinoma (p<0.0001), with no significant difference between papillary serous cystadenocarcinoma and MCOA (p=0.712). Finally, a nomogram consisting of age, grade, SEER stage, and AJCC stage was established and validated to predict the survival time, with C-indices of 0.743 and 0.731, respectively.
CONCLUSIONS
In summary, MCOA is uncommon, and age, grade, SEER stage, and AJCC stage are independent prognostic factors. Compared with other common malignant ovarian tumors, MCOA has a poor prognosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cystadenocarcinoma, Serous; Female; Humans; Middle Aged; Nomograms; Ovarian Neoplasms; Prognosis; Young Adult
PubMed: 34674727
DOI: 10.1186/s13048-021-00896-9 -
Frontiers in Immunology 2022Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2...
OBJECTIVE
Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2 in cancers.
METHODS
Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were used to analyze the mRNA expression of ADA1 and ADA2 in human normal cells and tumor tissues. The enzyme assay was used to detect the ADA1 and ADA2 activities in serum from cancer patients. The Kaplan-Meier (KM) plotter was used to analyze the prognostic value of ADA1 and ADA2. TIMER2.0 was used to explore how ADA1 and ADA2 correlate with immune infiltration and immune checkpoints. cBioPortal database was used to investigate the mutations of ADA1 and ADA2. LinkedOmics was used to screen the ADA1 and ADA2 expression-related genes.
RESULTS
ADA1 was significantly increased in several tumor tissues, including cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), thymoma (THYM), and uterine carcinosarcoma (UCS). ADA2 expression was significantly increased in esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), OV, PAAD, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). There were no significant changes in serum ADA1 activities in most cancers, while serum ADA2 activities were increased in most cancers. For prognosis, high ADA1 expression was associated with the poor survival in several cancers, including esophageal squamous cell carcinoma (ESCC), HNSC, KIRC, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC). However, high ADA2 expression showed a favorable prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), HNSC, KIRC, KIRP, LUAD, OV, PAAD, sarcoma, and THYM. ADA1 showed a moderate positive correlation with multiple infiltrating immune cells in most cancers. ADA2 was positively correlated with B cells, CD8 T cells, monocytes/macrophages, and dendritic cells (DCs) and was strongly negatively correlated with myeloid-derived suppressor cells. Function analysis showed that ADA1 expression-related genes were mainly enriched in cell division biological progression. However, ADA2-related genes were mainly associated with immune response.
CONCLUSION
As isoenzymes, ADA1 and ADA2 showed opposite prognostic values and different correlative patterns with immune infiltrating. These data demonstrated the distinct roles of ADA1 and ADA2 in cancer. ADA2 might act as a protective factor in cancer.
Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adenosine Deaminase; Carcinoma, Renal Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Head and Neck Neoplasms; Humans; Isoenzymes; Kidney Neoplasms; Lung Neoplasms; Melanoma; Pancreatic Neoplasms; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck; Melanoma, Cutaneous Malignant
PubMed: 35663977
DOI: 10.3389/fimmu.2022.903461 -
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 -
Translational Cancer Research Dec 2022Mucinous cystadenocarcinoma (MCA) mainly occurs in the ovary, pancreas, and appendix, whereas the breast is a rare primary site of occurrence. Invasive ductal carcinoma...
BACKGROUND
Mucinous cystadenocarcinoma (MCA) mainly occurs in the ovary, pancreas, and appendix, whereas the breast is a rare primary site of occurrence. Invasive ductal carcinoma (IDC) is the most common breast malignancy. Only 31 cases of the breast MCA have been reported in the English literature, and the coexistence of MCA and IDC in the breast are rare.
CASE DESCRIPTION
Here, we describe a 61-year-old postmenopausal woman with no family history of breast cancer or other breast-related diseases, who presented with a palpable mass in her left breast lasting for 2 months. On ultrasonography examination, the tumor was a cystic-solid lesion with clear boundary. Magnetic resonance imaging (MRI) showed a mass with low signal intensity on T1 weighted imaging and high signal intensity on T2 weighted imaging. Intraoperative frozen sections revealed metastatic tumor cells in one sentinel lymph node (1/4). She then underwent left modified radical mastectomy with axillary dissection. The post-operative pathological examination showed the tumor consisted mostly of MCA (60%), with a small proportion of intermediate-grade IDC. The MCA had a well-demarcated cystic structure with papillary projections and abundant mucoid material. The epithelium lining cystic spaces was tall columnar, with mucin-producing cells that had basally located nuclei. The degree of cytological atypia varied considerably. Axillary lymph nodes were normal (0/15). The MCA was triple-negative for estrogen receptor (ER), progesterone receptor (PR), and HER2, and positive for CK7 but negative for CK20. Through next-generation sequencing, no mutations in the and genes were identified in our case, which was not highlighted in prior cases. After surgery, the patient underwent eight cycles of chemotherapy, and she has been disease-free during the 10-month follow-up. In addition to detailing this instance of mixed MCA and IDC of the breast, we reviewed relevant literature and compare our findings with other patients who had breast MCAs.
CONCLUSIONS
Our results improved the understanding of mixed MCA and IDC, especially MCA, and provided a basis for its diagnosis and differential diagnosis from other metastatic diseases.
PubMed: 36644191
DOI: 10.21037/tcr-22-1596 -
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 -
Cureus Jun 2023Mucinous neoplasms are commonly seen in the ovaries and pancreas. Their occurrence in the retroperitoneum is uncommon. We present a case of a retroperitoneal mucinous...
Mucinous neoplasms are commonly seen in the ovaries and pancreas. Their occurrence in the retroperitoneum is uncommon. We present a case of a retroperitoneal mucinous cystadenocarcinoma in a 54-year-old female who presented with right flank pain. Imaging demonstrated an 8.6 × 7.9 cm mass at the anterior surface of the lower pole of the right kidney, suspicious for renal cell carcinoma. Serum tumor markers carbohydrate antigen 19-9 (CA 19-9) and cancer embryonic antigen (CEA) were within normal limits, and cancer antigen 125 (CA 125) was elevated. Surgical resection of the mass was performed. Intraoperatively, the mass was noted to lie in the retroperitoneum, unattached to the kidney. On gross examination, a 10.0 × 7.0 × 7.0 cm unilocular cystic structure with red-brown mucoid material was present. The inner lining was mostly smooth with areas of excrescences, covering less than 5% of the surface area. Microscopic examination showed cystic areas lined by mucinous epithelium with an underlying ovarian-type stroma. Solid areas showed features of a borderline papillary mucinous tumor with invasive carcinoma. A diagnosis of mucinous cystadenocarcinoma was made. Their occurrence in the retroperitoneum is unusual. Although rare, this entity should always be considered in the differential diagnosis of retroperitoneal cystic lesions.
PubMed: 37415996
DOI: 10.7759/cureus.39983 -
Frontiers in Oncology 2020The receptor tyrosine kinase mesenchymal-epithelial transition factor (MET) is frequently altered in cancers and is a common therapeutic target for cancers with MET...
BACKGROUND
The receptor tyrosine kinase mesenchymal-epithelial transition factor (MET) is frequently altered in cancers and is a common therapeutic target for cancers with MET variants. However, abnormal MET alterations and their associations with patient outcome across different cancer types have not been studied simultaneously. In this study, we try to fill the vacancy in a comprehensive manner and capture the full MET alteration spectrum.
METHODS
A total of 10,967 tumor samples comprising 32 cancer types from The Cancer Genome Atlas (TCGA) datasets were analyzed for MET abnormal expression, mutations, and copy number variants (CNVs).
RESULTS
MET abnormal expression, alteration frequency, mutation site distribution, and functional impact varied across different cancer types. Lung adenocarcinoma (LUAD) has most targetable mutations located in the juxtamembrane domain, and both high expression and amplification of MET are significantly associated with poor prognosis. Kidney renal papillary cell carcinoma (KIRP) harbored the third highest alteration frequency of MET, which was dominated by mutations. While most mutations were in the Pkinase_Tyr domain, a few were targetable. Pancreatic adenocarcinoma (PAAD) harbors very few alterations, but increased MET expression is associated with poor outcomes. Esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), and ovarian serous cystadenocarcinoma (OV) had similar characteristics: a high frequency of MET CNVs but relatively few MET mutations, and high MET expression associated with poor prognosis.
CONCLUSION
This study provided significant and comprehensive information regarding MET abnormal expression, alterations (mutations and CNVs), and their clinical associations among 32 cancer types and offered insights into the full MET alteration spectrum and its implications for prognosis and treatment.
PubMed: 33178590
DOI: 10.3389/fonc.2020.560615 -
Journal of the Egyptian National Cancer... Feb 2022High-grade serous ovarian carcinoma (HGSOC) is classified into four molecular subtypes; mesenchymal, proliferative, immunoreactive, and differentiated, with suggested...
BACKGROUND
High-grade serous ovarian carcinoma (HGSOC) is classified into four molecular subtypes; mesenchymal, proliferative, immunoreactive, and differentiated, with suggested different prognosis. Addressing the presence of histopathological and immunohistochemical differences in HGSOC that parallel the molecular subtypes can help in tailoring the management protocol to improve therapeutic response and patient outcome.
METHODS
This retrospective study was conducted on 85 specimens for cases of HGSOC. Cases were classified according to histopathological findings into mesenchymal, proliferative, immunoreactive, and differentiated subtypes. Cases were immunostained with ER, PR, Ki67, CD8, E-cadherin, and vimentin.
RESULTS
By applying histopathological data, cases were subdivided into 4 groups; mesenchymal type represented by 25 cases, proliferative type which included 14 cases, the immunoreactive type included 14 cases, and differentiated type represented by 32 cases; 13 of them had SET features and 19 had papillary architectural features. A significant correlation was found between Ki67 and proliferative subtype, as well as between CD8 and immunoreactive subtype. ER showed significantly higher expression in proliferative subtype in the group treated by primary debulking. CD8 showed a significant correlation with solid endometroid transitional (SET) pattern in the group that underwent interval debulking. In terms of prognosis, the shortest median progression-free survival (PFS) was for mesenchymal subtype, while the longest median PFS was for differentiated subtype with SET architectural pattern with statistically significant correlation. No correlation was found between any of the studied parameters and overall survival.
CONCLUSION
Histopathological features and immunohistochemistry can help to stratify HGSOC into prognostic distinct groups.
Topics: Cystadenocarcinoma, Serous; Humans; Ovarian Neoplasms; Prognosis; Progression-Free Survival; Retrospective Studies
PubMed: 35138498
DOI: 10.1186/s43046-022-00104-9 -
Case Reports in Oncology 2020Papillary cystadenocarcinoma is an uncommon disease with low-grade histological and clinical features. Although the tumor has the potential to produce regional lymph...
Papillary cystadenocarcinoma is an uncommon disease with low-grade histological and clinical features. Although the tumor has the potential to produce regional lymph node metastasis, there have been no reports of cases with distant metastasis. We describe a case of papillary cystadenocarcinoma arising from the maxilla that developed pulmonary metastasis 3 years after radical surgery of the primary tumor and regional lymph node. The histological findings were confirmed on resected specimens of the pulmonary nodule and a pathological diagnosis of a metastatic lesion derived from papillary cystadenocarcinoma was made. To our knowledge, this is the first report of the development of pulmonary metastasis in a patient with papillary cystadenocarcinoma. The present case suggests that papillary cystadenocarcinoma has the potential to produce lung metastasis in the clinical course. Based on our experience, we emphasize that long-term follow-up and/or careful examination are necessary in patients with cystadenocarcinoma, especially in patients with lymph node metastasis during the initial surgical therapy.
PubMed: 32774257
DOI: 10.1159/000507956 -
Frontiers in Molecular Biosciences 2020Angiotensin-converting enzyme 2 (ACE2) plays a pivotal role in the renin-angiotensin system and is closely related to coronavirus disease of 2019. However, the role of...
Angiotensin-converting enzyme 2 (ACE2) plays a pivotal role in the renin-angiotensin system and is closely related to coronavirus disease of 2019. However, the role of ACE2 in cancers remains unclear. We explored the pan-cancer expression patterns and prognostic value of ACE2 across multiple databases, including Oncomine, PrognoScan, Gene Expression Profiling Interactive Analysis, and Kaplan-Meier Plotter. Then, we investigated the correlations between ACE2 expression and immune infiltration in cancers. We found that tumor tissues had higher expression levels of ACE2 compared with normal tissue in the kidney and the liver and lower expression levels in the lung. High expression levels of ACE2 were beneficial to survival in ovarian serous cystadenocarcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and kidney renal clear cell carcinoma, although this was not the case in lung squamous cell carcinoma. For those with a better prognosis, there were significant positive correlations between ACE2 expression and immune infiltrates, including B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. In conclusion, ACE2 could serve as a pan-cancer prognostic biomarker and is correlated with immune infiltrates.
PubMed: 33088807
DOI: 10.3389/fmolb.2020.00189