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Computational and Structural... 2023Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor...
Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.
PubMed: 36659929
DOI: 10.1016/j.csbj.2022.12.049 -
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 -
Archives of Pathology & Laboratory... Jan 2023Mucinous lesions of the breast encompass many entities ranging from benign to malignant and nonneoplastic to neoplastic. Lesions discussed under this category are... (Review)
Review
CONTEXT.—
Mucinous lesions of the breast encompass many entities ranging from benign to malignant and nonneoplastic to neoplastic. Lesions discussed under this category are mucocele-like lesion, mucinous carcinoma, mucinous micropapillary carcinoma, solid papillary carcinoma, mucinous cystadenocarcinoma, mucoepidermoid carcinoma, invasive lobular carcinoma with extracellular mucin, mucinous ductal carcinoma in situ, and metastasis.
OBJECTIVE.—
To review clinical, pathologic, and molecular features of mucinous lesions of the breast, their differential diagnoses, and challenging features on core needle biopsies.
DATA SOURCES.—
The existing scientific and clinical literature as of December 2021.
CONCLUSIONS.—
The category of mucinous lesions of the breast is vast and the differential diagnosis can be challenging, especially on core needle biopsies. In all cases, clinical, radiologic, and pathologic correlation is necessary to reach a comprehensive diagnosis. Given that the prognosis and management of each entity is different, being aware of these entities and their nuances is critical for a pathologist to guide accurate management.
Topics: Female; Humans; Adenocarcinoma, Mucinous; Biopsy, Large-Core Needle; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating
PubMed: 36577093
DOI: 10.5858/arpa.2022-0054-RA -
Surgical Case Reports Nov 2022A hematoma that gradually increases over a chronic course of months or longer is defined as a chronic expanding hematoma (CEH). CEHs often develop in the limbs and on...
BACKGROUND
A hematoma that gradually increases over a chronic course of months or longer is defined as a chronic expanding hematoma (CEH). CEHs often develop in the limbs and on body surfaces that are susceptible to external stimuli. CEHs in the intrathoracic or intraperitoneal organs are uncommon, with liver CEHs being particularly rare worldwide.
CASE PRESENTATION
A 57-year-old woman was previously diagnosed with a giant cyst in the right liver lobe, with a longer axis of approximately 15 cm. Abdominal ultrasonography findings suggested a complex cyst, and she was referred to our hospital for further inspection. Although CEH was suspected, it was difficult to exclude malignant diseases such as intraductal papillary neoplasm of the bile duct and cystadenocarcinoma. There was a possibility of malignant disease and the exclusion of surrounding organs due to tumor growth. Therefore, a right hepatectomy was performed. Pathological examination revealed a pseudocyst containing a clot, which was consistent with CEH.
CONCLUSIONS
CEH rarely occurs in the liver; however, it is necessary to consider CEH when a slow-growing hepatic mass that shows a mosaic pattern on magnetic resonance imaging is found.
PubMed: 36414762
DOI: 10.1186/s40792-022-01548-w -
The Journal of International Medical... Nov 2022High-grade serous ovarian cancer (HGSOC) is a deadly malignancy. Homeobox protein A9 () is linked with serous papillary histotype differentiation, and inappropriate...
OBJECTIVE
High-grade serous ovarian cancer (HGSOC) is a deadly malignancy. Homeobox protein A9 () is linked with serous papillary histotype differentiation, and inappropriate expression is a step in ovarian cancer that induces aberrant differentiation. This study aimed to reveal the significance of in HGSOC.
METHODS
mRNA and protein expression were examined by quantitative PCR and immunohistochemistry, respectively. The chi-square test was used to evaluate associations between expression and clinical characteristics. The prognostic value of was calculated by the Kaplan-Meier method. The Kaplan-Meier Plotter database was used to assess the prognostic value of .
RESULTS
The mRNA and protein expression of were significantly upregulated in chemotherapy-resistant HGSOC compared with chemotherapy-sensitive HGSOC. The chi-square test showed that high expression was significantly related with grade, clinical stage, and residual disease. High expression was significantly associated with poor prognosis. The Kaplan-Meier Plotter database further confirmed these results. Cox hazard regression showed that high expression was an independent prognostic factor for survival in HGSOC patients.
CONCLUSION
This study showed that expression was associated with chemotherapy resistance and poor outcomes in HGSOC patients. High expression might be a prognostic indicator for HGSOC.
Topics: Humans; Female; Cystadenocarcinoma, Serous; Kaplan-Meier Estimate; Prognosis; Ovarian Neoplasms; Gene Expression; RNA, Messenger
PubMed: 36366735
DOI: 10.1177/03000605221135864 -
Clinical & Translational Oncology :... Feb 2023The main function of cartilage oligomeric matrix protein (COMP) is to maintain the synthesis and stability of the extracellular matrix by interacting with collagen. At...
PURPOSE
The main function of cartilage oligomeric matrix protein (COMP) is to maintain the synthesis and stability of the extracellular matrix by interacting with collagen. At present, there are relatively few studies on the role of this protein in tumors. This study aimed to explore the relationship between COMP and pan-cancer, and analyzed its diagnostic and prognostic value.
METHODS
The Cancer Genome Atlas database, the Genotype-Tissue Expression database and the Cancer Cell Line Encyclopedia database was used for gene expression analysis. The receiver operating characteristic curve was used to assess the diagnostic value of COMP in pan-cancer. Kaplan-Meier plots were used to assess the relationship between COMP expression and prognosis of cancers. R software v4.1.1 was used for statistical analysis, and the ggplot2 package was used for visualization.
RESULTS
COMP was significantly overexpressed in 15 human cancers and showed significantly difference in 12 molecular subtypes and 16 immune subtypes. In addition, the expression of COMP is associated with tumor immune evasion. The ROC curve showed that the expression of COMP could predict the occurrence of 16 kinds of tumors with relative accuracy, including adrenocortical carcinoma (ACC) (AUC = 0.737), breast invasive carcinoma (BRCA) (AUC = 0.896), colon adenocarcinoma (COAD) (AUC = 0.760), colon adenocarcinoma/rectum adenocarcinoma esophageal carcinoma (COADREAD) (AUC = 0.775), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC) (AUC = 0.875), kidney renal papillary cell carcinoma (KIRP) (AUC = 0.773), kidney chromophobe (KICH) (AUC = 0.809), ovarian serous cystadenocarcinoma (OV) (AUC = 0.906), prostate adenocarcinoma (PRAD) (AUC = 0.721), pancreatic adenocarcinoma (PAAD) (AUC = 0.944), rectum adenocarcinoma (READ) (AUC = 0.792), skin cutaneous melanoma (SKCM) (AUC = 0.746), stomach adenocarcinoma (STAD) (AUC = 0.711), testicular germ cell tumors (TGCT) (AUC = 0.823), thymoma (THYM) (AUC = 0.777) and uterine carcinosarcoma (UCS) (AUC = 0.769). Furthermore, COMP expression was correlated with overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in ACC (OS, HR = 4.95, DSS, HR = 5.55, PFI, HR = 2.79), BLCA (OS, HR = 1.59, DSS, HR = 1.72, PFI, HR = 1.36), KIRC (OS, HR = 1.36, DSS, HR = 1.94, PFI, HR = 1.57) and COADREAD (OS, HR = 1.46, DSS, HR = 1.98, PFI, HR = 1.43). We selected previously unreported bladder urothelial carcinoma (BLCA) for further study and found that COMP could be an independent risk factor for OS, DSS and PFI. Moreover, we found differentially expressed genes of COMP in BLCA and obtained top 10 hub genes, including LGR4, LGR5, RSPO2, RSPO1, RSPO3, RNF43, ZNRF3, FYN, LYN and SYK. Finally, we verified the function of COMP at the cellular level by using J82 and T24 cells and found that knockdown of COMP could significantly inhibit migration and invasion. This finding supports that COMP could be a potential biomarker for pan-cancer diagnosis and prognosis encompassing tumor microenvironment, disease stage and prognosis.
CONCLUSION
This finding supports that COMP could be a potential biomarker for pan-cancer diagnosis and prognosis encompassing tumor microenvironment, disease stage and prognosis.
Topics: Male; Humans; Adenocarcinoma; Melanoma; Cartilage Oligomeric Matrix Protein; Carcinoma, Transitional Cell; Skin Neoplasms; Colonic Neoplasms; Pancreatic Neoplasms; Urinary Bladder Neoplasms; Biomarkers; Rectal Neoplasms; Carcinoma, Renal Cell; Kidney Neoplasms; Prognosis; Melanoma, Cutaneous Malignant
PubMed: 36255654
DOI: 10.1007/s12094-022-02968-8 -
Diagnostic Pathology Oct 2022Uterine somatic choriocarcinoma is a rare, clinically aggressive malignant tumor. They frequently concur with other cancer. However, the molecular pathogenesis between...
BACKGROUND
Uterine somatic choriocarcinoma is a rare, clinically aggressive malignant tumor. They frequently concur with other cancer. However, the molecular pathogenesis between somatic choriocarcinoma and the concurrent carcinoma has rarely been addressed to date.
CASE PRESENTATION
We report a 68-years old Chinese woman with a uterine choriocarcinoma arising from serous carcinoma. The patient underwent radical surgery including total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy and pelvic lymph node resection. She received 10 courses of post-operative chemotherapy. She died of disease 13 months after her surgery. Microscopically, the tumor showed a biphasic pattern of choriocarcinoma and serous carcinoma. The choriocarcinomatous component showed a combination of cytotrophoblast, intermediate trophoblast and syncytiotrophoblast with hemorrhage and necrosis. The component of serous carcinoma was characterized by solid sheets of small cells with marked nuclear atypia and occasional glandular and papillary formation. PD-L1 was exclusively expressed in the choriocarcinomatous component. Next-generation sequencing revealed that the genetic abnormalities were overlapping between the two components.
Topics: Aged; B7-H1 Antigen; Carcinoma; Choriocarcinoma; Cystadenocarcinoma, Serous; Female; High-Throughput Nucleotide Sequencing; Humans; Immunochemistry; Postmenopause
PubMed: 36229840
DOI: 10.1186/s13000-022-01262-z -
Computational and Structural... 2022Tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2) is encoded by TNFAIP8L2 and is a newly identified negative regulator of natural and acquired immunity that...
Tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2) is encoded by TNFAIP8L2 and is a newly identified negative regulator of natural and acquired immunity that plays a critical function in maintaining immune homeostasis. Recently, CAR-NK immune cell therapy has been a focus of major research efforts as a novel cancer therapeutic strategy. TIPE2 is a potential checkpoint molecule for immune cell maturation and antitumor immunity that could be used as a novel NK cell-based immunotherapeutic approach. In this study, we explored the expression of TNFAIP8L2 across various tumor types and found that TNFAIP8L2 was highly expressed in most tumor types and correlated with prognosis. Survival analysis showed that TNFAIP8L2 expression was predictive of improved survival in cervical-squamous-cell-carcinoma (CESC), sarcoma (SARC) and skin-cutaneous-melanoma (SKCM). Conversely, TNFAIP8L2 expression predicted poorer survival in acute myeloid leukemia (LAML), lower-grade-glioma (LGG), kidney-renal-clear-cell-carcinoma (KIRC) and uveal-melanoma (UVM). Analysis of stemness features and immune cell infiltration indicated that TNFAIP8L2 was significantly associated with cancer stem cell index and increased macrophage and dendritic cell infiltration. Our data suggest that TNFAIP8L2 may be a novel immune checkpoint biomarker across different tumor types, particularly in LAML, LGG, KIRC and UVM, and may have further utility as a potential target for immunotherapy.
PubMed: 36187930
DOI: 10.1016/j.csbj.2022.09.021 -
Zhonghua Yi Xue Za Zhi Aug 2022To analyze clinicopathological characteristics of patients with uterine papillary serous carcinoma (UPSC) in China, and investigate roles of TXNDC17 protein in UPSC...
To analyze clinicopathological characteristics of patients with uterine papillary serous carcinoma (UPSC) in China, and investigate roles of TXNDC17 protein in UPSC clinicopathological characteristics and prognosis. Fifty-five patients with UPSC treated in Women's Hospital School of Medicine Zhejiang University from 2003 to 2016 were analysed retrospectively. Immunohistochemistry (IHC) were performed to TXNDC17 and BECN1 (Beclin 1 protein, a key regulator of autophagy) protein expression respectively. Kaplan-Meier was used to calculate the cumulative survival rate, Log-rank test was performed to compare the difference in cumulative survival rate among patients with different clinicopathological characteristics, and Cox regression model was used to analyze the related between TXNDC17 expression and prognosis of UPSC patients. The median age of the 55 UPSC patients was 63(49, 79) years, 43.6%(24/55) with late stages (stage Ⅲ/Ⅳ), and 32.7 % (18/55) exhibiting more than half of myometrium invasion were enrolled. Notably, 28 (50.9%) patients had TXNDC17 protein overexpression, and associated with BECN1 overexpression(=0.023). Besides, co-expression of TXNDC17 and BECN1 occurred at an advanced stage and deep myometrial invasion (=0.013,0.009). The cumulative survival rate of TXNDC17 overexpression(37.4% vs 91.5%),FIGO Ⅲ/Ⅳ stage(44.1% vs 70.1%), deep myometrium invasion(36.1% vs 75.4%) and BECN1 overexpression(0 vs 83.0%)patients was low (<0.05). The multivariate proportional hazards model revealed that myometrial invasion and TXNDC17 overexpression were associated with prognosis of UPSC patients. This study shows that TXNDC17 overexpression is associate with poor survival in UPSC patients. Co-expression of TXNDC17 and BECN1 shows characteristics of advanced stages and deep myometrial invasion. TXNDC17 may be a potential predictor or target in UPSC therapeutics..
Topics: Carcinoma; Cystadenocarcinoma, Serous; Female; Humans; Neoplasm Staging; Prognosis; Retrospective Studies; Uterine Neoplasms
PubMed: 36008321
DOI: 10.3760/cma.j.cn112137-20220614-01317 -
Human Pathology Oct 2022As there is limited literature on paratesticular tumors of müllerian and mesothelial origin, we reviewed archived cases of serous borderline tumors (n = 15),...
A diagnostic approach to paratesticular lesions with tubulopapillary architecture: a series of 16 serous borderline tumors/low-grade serous carcinoma and 14 well-differentiated papillary mesothelial tumors and mesothelioma.
As there is limited literature on paratesticular tumors of müllerian and mesothelial origin, we reviewed archived cases of serous borderline tumors (n = 15), low-grade serous carcinoma (n = 1), well-differentiated papillary mesothelial tumors (WDPMTs; n = 2), and mesothelioma (n = 12), for relevant clinicopathologic features. Molecular profiling data from the American Association for Cancer Research (AACR) GENIE registry was accessed for 8 additional patients with testicular mesothelioma. For tumors of mesothelial origin, the median age at surgical excision was 62 years, the median size was 4.5 cm, and they consistently exhibited positivity for mesothelial markers (CK5/6, calretinin, WT1, and D2-40). Recurrent alterations of the NF2 gene were identified in 3 of 8 patients (38%), and alterations of BAP1 and CDKN2A were relatively infrequent. While one patient with WDPMT had a recurrence, a second patient with WDPMT progressed to a biphasic mesothelioma 2 years after initial resection. For tumors of müllerian origin, the median age at surgical excision was 45 years, the median size was 2.5 cm, and these exhibited consistent positivity for ER, WT1, and PAX8. Although no recurrences were documented in patients with serous borderline tumors, a single patient with a low-grade serous carcinoma developed widely metastatic disease and died of disease-related complications. Our study emphasizes the need for close clinical follow-up in patients with WDPMT and highlights the prognostic significance of documenting invasive behavior in tumors of müllerian origin as they can have an aggressive clinical course. Finally, our results suggest that NF2 alterations may play an important role in the pathogenesis of testicular mesothelioma.
Topics: Biomarkers, Tumor; Calbindin 2; Cystadenocarcinoma, Serous; Female; Humans; Hyperplasia; Male; Mesothelioma; Mesothelioma, Malignant; Ovarian Neoplasms; Peritoneal Neoplasms; Testicular Neoplasms
PubMed: 35809685
DOI: 10.1016/j.humpath.2022.06.028