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Journal of Cellular and Molecular... Jul 2018Septins are a conserved family of cytoskeletal GTPases present in different organisms, including yeast, drosophila, Caenorhabditis elegans and humans. In humans, septins...
Septins are a conserved family of cytoskeletal GTPases present in different organisms, including yeast, drosophila, Caenorhabditis elegans and humans. In humans, septins are involved in various cellular processes, including exocytosis, apoptosis, leukemogenesis, carcinogenesis and neurodegeneration. Septin 7 is unique out of 13 human septins. Mammalian septin 6, septin 7, septin 2 and septin 9 coisolate together in complexes to form the core unit for the generation of the septin filaments. Physiological septin filaments are hetero-oligomeric complexes consisting of core septin hexamers and octamers. Furthermore, septin 7 plays a crucial role in cytokinesis and mitosis. Septin 7 is localized to the filopodia and branches of developing hippocampal neurons, and is the most abundant septin in the adult rat forebrain as well as a structural component of the human and mouse sperm annuli. Septin 7 is crucial to the spine morphogenesis and dendrite growth in neurons, and is also a structural constituent of the annulus in human and mouse sperm. It can suppress growth of some tumours such as glioma and papillary thyroid carcinoma. However, the molecular mechanisms of involvement of septin 7 in human disease, especially in the development of cancer, remain unclear. This review focuses on the structure, function and mechanism of septin 7 in vivo, and summarizes the role of septin 7 in cell proliferation, cytokinesis, nervous and reproductive systems, as well as the underlying molecular events linking septin 7 to various diseases, such as Alzheimer's disease, schizophrenia, neuropsychiatric systemic lupus erythematosus, tumour and so on.
Topics: Alzheimer Disease; Calcium; Cell Cycle Proteins; Cell Proliferation; Humans; Lupus Vasculitis, Central Nervous System; Nervous System; Schizophrenia; Septins
PubMed: 29602250
DOI: 10.1111/jcmm.13623 -
Veterinary Pathology Mar 2024One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The...
One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review was to analyze the methods and prognostic relevance of histologically measuring mitotic activity that have been reported for canine tumors in the literature. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and nonsystematic (Google Scholar) literature search and eligibility screening process. Mitotic activity methods encompassed the mitotic count (MC, number of mitotic figures per tumor area) in 126 studies, presumably the MC (method not specified) in 6 studies, and the mitotic index (MI, number of mitotic figures per number of tumor cells) in 5 studies. A particularly high risk of bias was identified based on the available details of the MC methods and statistical analyses, which often did not quantify the prognostic discriminative ability of the MC and only reported values. A significant association of the MC with survival was found in 72 of 109 (66%) studies. However, survival was evaluated by at least 3 studies in only 7 tumor types/groups, of which a prognostic relevance is apparent for mast cell tumors of the skin, cutaneous melanoma, and soft tissue tumor of the skin and subcutis. None of the studies using the MI found a prognostic relevance. This review highlights the need for more studies with standardized methods and appropriate analysis of the discriminative ability to prove the prognostic value of the MC and MI in various tumor types. Future studies are needed to evaluate the influence of the performance of individual pathologists on the appropriateness of prognostic thresholds and investigate methods to improve interobserver reproducibility.
PubMed: 38533804
DOI: 10.1177/03009858241239565 -
APMIS : Acta Pathologica,... Mar 2020Intraductal carcinomas (IDCs) are rare, not well-characterized salivary gland tumors. A systematic literature review of pure IDCs (without stromal invasion) of low-grade...
Intraductal carcinomas (IDCs) are rare, not well-characterized salivary gland tumors. A systematic literature review of pure IDCs (without stromal invasion) of low-grade (LG-IDCs) or high-grade (HG-IDCs) was performed: IDCs were classified using the apocrine (AR+/S100-) vs intercalated (S100+/AR-) classification. Eighty-two LG-IDCs and 11 HG-IDCs were identified (84% parotid; 11% oral; 3% submandibular; 1% lacrimal; and 1% unknown). Out of 11 HG-IDCs, 2 HG-IDCs (18%) recurred as HG-IDC or invasive carcinoma. IDCs were classified as follows: intercalated (30%); mixed apocrine and intercalated (27%); apocrine (11%); oncocytic (6%); intercalated with focal oncocytic features (1%); and unclassifiable (25%). Double AR/S100 expressors (4%) or discrepancies between morphology and immunophenotype (9%) were found. Apocrine features and necrosis were more frequent in HG-IDCs (55%; 45%). Pleomorphism favored HG-IDCs (especially when combined with >10 mitoses/10 HPFs and/or Ki67 index >10%), being associated with apocrine areas at least in 3 HG-IDCs (27%). IDCs were typically mammaglobin+/ER-/PR-/DOG1-. No immunomarker clearly distinguished HG-IDCs from LG-IDCs. About 57% IDCs (16 LG-IDCs, 1 HG-IDC) showed RET rearrangements, including NCOA4-RET (eight intercalated and two unclassifiable IDCs) and TRIM27-RET fusions (two mixed IDCs). No ETV6, ALK-1, ROS, NTRK3, MAML2, MAML3, or PLAG1 rearrangements were identified. Complete excision and total sampling should exclude invasive areas.
Topics: Biomarkers, Tumor; Carcinoma, Intraductal, Noninfiltrating; Humans; Neoplasm Recurrence, Local; Salivary Gland Neoplasms; Salivary Glands
PubMed: 31697865
DOI: 10.1111/apm.13009 -
Head and Neck Pathology Jun 2020Solitary fibrous tumors (SFT) arising in the head and neck region are uncommon yet well-recognized entities. Their biologic behavior and management still need to be... (Meta-Analysis)
Meta-Analysis
Solitary fibrous tumors (SFT) arising in the head and neck region are uncommon yet well-recognized entities. Their biologic behavior and management still need to be elucidated. Systematically reviewing all published cases of SFT involving the head and neck region since 1991, a pooled meta-analysis was conducted to evaluate various demographic and tumor characteristics. 587 SFT in the head and neck have been reported; 343 met pooled analysis inclusion criteria. 61% of cases presented as a new mass; 89% were painless. Median onset of symptoms prior to evaluation was 8 months. Pre-operative local invasion and malignant histological features (hemorrhage, necrosis, mitoses > 4/10 hpf) were not statistically associated with decreased recurrence-free survival. Positive surgical margins was the only factor associated with shorter recurrence-free survival (p < 0.001). The evidence presented herein reveals novel associations between clinical presentation and tumor characteristics that provide otolaryngologists with new insight into SFT tumor behavior, thus prompting further investigations.
Topics: Head and Neck Neoplasms; Humans; Solitary Fibrous Tumors
PubMed: 31338745
DOI: 10.1007/s12105-019-01058-6 -
Dermatologic Surgery : Official... Sep 2014The seventh edition of the American Joint Committee on Cancer guidelines recognize mitotic rate (MR) as a component of the staging criteria for cutaneous melanomas with... (Review)
Review
BACKGROUND
The seventh edition of the American Joint Committee on Cancer guidelines recognize mitotic rate (MR) as a component of the staging criteria for cutaneous melanomas with a Breslow depth ≤1 mm.
OBJECTIVE
This review discusses the evidence behind the threshold of 1 mitosis per square millimeter as a prognostic variable in thin melanomas, particularly because it relates to the decision to pursue a sentinel lymph node biopsy (SLNB).
MATERIALS AND METHODS
We performed a systematic review using the PubMed database to identify articles that contain prognostic information for thin melanomas based on MR and sentinel lymph node (SLN) status.
RESULTS
Although the threshold of a single mitosis correlates with a statistically significant decrease in survival rates for patients with thin melanomas, the clinical relevance remains questionable particularly because it relates to the decision to pursue an SLNB.
CONCLUSION
A single mitosis in thin melanomas does not increase the risk of a positive SLN so much that SLN biopsy should be routinely performed for this cohort.
Topics: Humans; Lymphatic Metastasis; Melanoma; Mitotic Index; Patient Selection; Prognosis; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 25072127
DOI: 10.1097/01.DSS.0000452619.94264.ff -
Zhonghua Bing Li Xue Za Zhi = Chinese... Aug 2020To investigate the clinicopathological features, diagnosis, differential diagnosis, and molecular alterations of malignant gastrointestinal neuroectodermal tumor...
To investigate the clinicopathological features, diagnosis, differential diagnosis, and molecular alterations of malignant gastrointestinal neuroectodermal tumor (MGNET). Four cases of MGNET were collected at Fujian Provincial Hospital, from July 2013 to January 2019. H&E and immunohistochemical staining were retrospectively evaluated, together with genetic mutation analysis of EWSR1. The relevant literature was systematically reviewed. There were two male and two female patients, with an age range of 34-81 (median 57) years. Tumor sizes ranged from 5-9 (median 6.8) cm. Microscopy showed diffuse and flaky growth of tumor cells, some of which were small and round. The tumor cells were arranged in solid, flaky, nested or pseudoadenoid patterns. The tumor cells were epithelioid, oval, short spindled, or small, with round or oval nuclei. The cytoplasm was eosinophilic or clear. Osteoclast-like multinucleated giant cells were scattered focally. Mitosis was about (2-10)/10 HPF. Immunohistochemically, the tumor cells were positive for S-100 protein (4/4), SOX10 (4/4), Syn (2/4), INI1 (4/4), H3K27Me3 (4/4) and vimentin (4/4). Ki-67 index was 15%-90%. Gene mutation detection confirmed EWSR1 mutation in all four cases, and C-KIT/PDGFRα genes were not mutated in two cases. MGNET is a rare high grade malignant soft tissue tumor. The diagnosis is based on clinicopathological, immunophenotypic, and molecular pathology features. The primary treatment for MGNET is complete surgical excision and chemotherapy; the prognosis is poor.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Male; Middle Aged; Neuroectodermal Tumors; Retrospective Studies; S100 Proteins
PubMed: 32746550
DOI: 10.3760/cma.j.cn112151-20191204-00780 -
Journal of Pineal Research Nov 2020Melatonin is a ubiquitous molecule with a broad spectrum of functions including widespread anti-cancer activities. Identifying how melatonin intervenes in complex... (Meta-Analysis)
Meta-Analysis
Melatonin is a ubiquitous molecule with a broad spectrum of functions including widespread anti-cancer activities. Identifying how melatonin intervenes in complex molecular signaling at the gene level is essential to guide proper therapies. Using meta-analysis approach, herein we examined the role of melatonin in regulating the expression of 46 microRNAs (miRNAs) and their target genes in breast, oral, gastric, colorectal, and prostate cancers, and glioblastoma. The deregulated miRNA-associated target genes revealed their involvement in the regulation of cellular proliferation, differentiation, apoptosis, senescence, and autophagy. Melatonin changes the expression of miRNA-associated genes in breast, gastric, and oral cancers. These genes are associated with cellular senescence, the hedgehog signaling pathway, cell proliferation, p53 signaling, and the hippo signaling pathway. Conversely, colorectal and prostate cancers as well as glioblastoma and oral carcinoma present a clear pattern of less pronounced changes in the expression of miRNA-associated genes. Most notably, colorectal cancer displayed a unique molecular change in response to melatonin. Considering breast cancer network complexity, we compared the genes found during the meta-analysis with RNA-Seq data from breast cancer-bearing mice treated with melatonin. Mechanistically, melatonin upregulated genes associated with immune responses and apoptotic processes, whereas it downregulated genes involved in cellular aggressiveness/metastasis (eg, mitosis, telomerase activity, and angiogenesis). We further characterized the expression profile of our gene subsets with human breast cancer and found eight upregulated genes and 16 downregulated genes that were appositively correlated with melatonin. Our results pose a multi-dimension network of tumor-associated genes regulated by miRNAs potentially targeted by melatonin.
Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Melatonin; MicroRNAs; Neoplasms; RNA, Neoplasm
PubMed: 32910542
DOI: 10.1111/jpi.12693 -
European Journal of Endocrinology Dec 2022Pediatric adrenocortical carcinoma (pACC) is rare and prognostic stratification remains challenging. We summarized the clinical prognostic factors of pACC and determined...
OBJECTIVE
Pediatric adrenocortical carcinoma (pACC) is rare and prognostic stratification remains challenging. We summarized the clinical prognostic factors of pACC and determined the prognostic value of the pediatric scoring system (pS-GRAS) in adaption to the recommendation (S-GRAS) of the European Network for the Study of Adrenal Tumors for the classification of adult ACC.
DESIGN
Analysis of pACC patients of 33 available retrospective studies in the literature.
METHODS
We searched the PubMed and Embase databases for manuscripts regarding pACC. The pS-GRAS score was calculated as a sum of tumor stage (1 = 0; 2-3 = 1; 4 = 2 points), grade (Ki67 index/rate of mitosis 0-9%/low = 0; 10-19%/intermediate = 1; ≥20%/high = 2 points), resection status (R0 = 0; RX = 1; R1 = 2; R2 = 3 points), age (<4 years = 0; ≥4 years = 1 point), hormone-related symptoms (androgen production = 0; glucocorticoid/mixed/no hormone production = 1 point) generating 10 scores and 4 groups (1: 0-2, 2: 3-4, 3: 5, 4: 6-9). The primary endpoint was overall survival (OS).
RESULTS
We included 733 patients. The median age was 2.5 years and >85% of pACC showed hormone activity (mixed 50%, androgen 29%, glucocorticoid 21%). Androgen production was associated with a superior OS. Increasing age correlated with higher rates of inactive or only glucocorticoid-producing tumors, advanced tumor stage, and case fatality. Especially infants < 4 years showed more often low-risk constellations with an increased OS for all tumor stages. The pS-GRAS score correlated with clinical outcome; median OS was 133 months (95% CI: 36-283) in group 1 (n = 49), 110 months (95% CI: 2.9-314) in group 2 (n = 57), 49 months (95% CI: 5.8-278) in group 3 (n = 18), and 16 months (95% CI: 2.4-267) in group 4; (n = 11) P < 0.05).
CONCLUSION
The pS-GRAS score seems to have a high predictive value in the pACC patients, may serve as a helpful tool for risk stratification in future studies, and should be evaluated prospectively in an international context.
Topics: Child; Child, Preschool; Humans; Infant; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Androgens; Glucocorticoids; Ki-67 Antigen; Prognosis; Retrospective Studies
PubMed: 36193775
DOI: 10.1530/EJE-22-0173 -
BMC Surgery Aug 2019By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical modality for duodenal gastrointestinal stromal tumors (GISTs).
METHODS
Two authors independently searched PubMed, Web of Science, Embase, and the Cochrane Library for published articles comparing the long-term prognostic and clinicopathological factors of duodenal GIST patients undergoing PD versus LR. Relevant information was extracted and analyzed.
RESULTS
After screening, 10 items comprising 623 cases were eventually included. This meta-analysis explicitly indicated that PD treatment was associated with worse long-term prognosis (hazard ratio = 1.93; 95% confidence interval [CI], 1.39-2.69; p < 0.001; I = 0) and more complications (odds ratio [OR] = 2.90; 95% CI, 1.90-4.42; p < 0.001; I = 10%) than LR treatment. Nevertheless, for duodenal GISTs, PD was related to the following clinicopathological features: invasion of the second part of the duodenum (OR = 3.39; 95% CI, 1.69-6.79; p < 0.001; I = 50%), high-degree tumor mitosis (> 5/50 high-power fields; OR = 2.24; 95% CI, 1.42-3.52; p < 0.001; I = 0), and high-risk classification (OR = 3.17; 95% CI; 2.13-4.71; p < 0.001; I = 0).
CONCLUSIONS
Since PD is associated with worse long-term prognosis and more complications, its safety and efficacy should be ascertained. Our findings recommend the use of LR to obtain negative incision margins when conditions permit it.
Topics: Duodenal Neoplasms; Duodenum; Gastrointestinal Stromal Tumors; Humans; Margins of Excision; Middle Aged; Pancreaticoduodenectomy; Prognosis
PubMed: 31455328
DOI: 10.1186/s12893-019-0587-4 -
Veterinary Pathology Mar 2024Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an...
Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an analysis of all available references on mitotic activity in feline tumors to provide an overview of the assessment methods and prognostic value. A systematic literature search in PubMed and Scopus and a nonsystematic search in Google Scholar were conducted. All articles on feline tumors that correlated mitotic activity with patient outcome were identified. Data analysis revealed that of the 42 eligible articles, mitotic count (MC, mitotic figures/tumor area) was evaluated in 39 studies, and mitotic index (MI, mitotic figures/tumor cells) in 3 studies. The risk of bias was considered high for most studies (26/42, 62%) based on small study populations, insufficient details of the MC/MI methods, and lack of statistical measures for diagnostic accuracy or effect on outcome. The MC/MI methods varied between studies. A significant association of MC with survival was determined in 20 of 28 (71%) studies (10 studies evaluated other outcome metrics or provided individual patient data), while 1 study found an inverse effect. Three tumor types had at least 4 studies, and a prognostic association with survival was found in 5 of 6 studies on mast cell tumors, 5 of 5 on mammary tumors, and 3 of 4 on soft-tissue sarcomas. MI was shown to correlate with survival for mammary tumors by 2 research groups; however, comparisons to MC were not conducted. Further studies with standardized mitotic activity methods and appropriate statistical analysis for discriminant ability of patient outcome are needed to infer the prognostic value of MC and MI.
PubMed: 38533803
DOI: 10.1177/03009858241239566