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Virchows Archiv : An International... Dec 2017Typical (TCs) and atypical carcinoids (ACs) are defined based on morphological criteria, and no grading system is currently accepted to further stratify these entities....
Typical (TCs) and atypical carcinoids (ACs) are defined based on morphological criteria, and no grading system is currently accepted to further stratify these entities. The 2015 WHO classification restricts the Ki-67 role to biopsy or cytology samples, rather than for prognostic prediction. We aimed to investigate whether values and patterns of Ki-67 alone would allow for a clinically meaningful stratification of lung carcinoids, regardless of histological typing. Ki-67 proliferation index and pattern (homogeneous versus heterogeneous expression) were assessed in a cohort of 171 TCs and 68 ACs. Cases were subdivided into three Ki-67 ranges (<4/4-9/≥10%). Correlations with clinicopathological data, univariate and multivariate survival analyses were performed. The majority of cases (61.5%) belonged to the <4% Ki-67 range; 25.1 and 13.4% had a proliferation index of 4-9% and ≥10%, respectively. The <4% Ki-67 subgroup was significantly enriched for TCs (83%, p < 0.0001); ACs were more frequent in the subgroup showing Ki-67 ≥ 10% (75%, p < 0.0001). A heterogeneous Ki-67 pattern was preferentially seen in carcinoids with a Ki-67 ≥10% (38%, p < 0.02). Mean Ki-67 values ≥4 and ≥10% identified categories of poor prognosis both in terms of disease-free and overall survival (p = 0.003 and <0.0001). At multivariate analysis, the two thresholds did not retain statistical significance; however, a Ki-67 ≥ 10% identified a subgroup of dismal prognosis even within ACs (p = 0.03) at univariate analysis. Here, we describe a subgroup of lung carcinoids showing brisk proliferation activity within the necrosis and/or mitotic count-based categories. These patients were associated with specific clinicopathological characteristics, to some extent regardless of histological subtyping.
Topics: Adult; Aged; Biomarkers, Tumor; Carcinoid Tumor; Female; Humans; Kaplan-Meier Estimate; Ki-67 Antigen; Lung Neoplasms; Male; Middle Aged; Mitotic Index; Prognosis; Proportional Hazards Models
PubMed: 28631159
DOI: 10.1007/s00428-017-2177-0 -
Virchows Archiv : An International... Jan 2024Oral epithelial dysplasia (OED) is diagnosed and graded using a range of histological features, making grading subjective and challenging. Mitotic counting and...
Oral epithelial dysplasia (OED) is diagnosed and graded using a range of histological features, making grading subjective and challenging. Mitotic counting and phosphohistone-H3 (PHH3) staining have been used for the prognostication of various malignancies; however, their importance in OED remains unexplored. This study conducts a quantitative analysis of mitotic activity in OED using both haematoxylin and eosin (H&E)-stained slides and immunohistochemical (IHC) staining for PHH3. Specifically, the diagnostic and prognostic importance of mitotic number, mitotic type and intra-epithelial location is evaluated. Whole slide images (WSI) of OED (n = 60) and non-dysplastic tissue (n = 8) were prepared for analysis. Five-year follow-up data was collected. The total number of mitosis (TNOM), mitosis type and intra-epithelial location was manually evaluated on H&E images and a digital mitotic count performed on PHH3-stained WSI. Statistical associations between these features and OED grade, malignant transformation and OED recurrence were determined. Mitosis count increased with grade severity (H&E: p < 0.005; IHC: p < 0.05), and grade-based differences were seen for mitosis type and location (p < 0.05). The ratio of normal-to-abnormal mitoses was higher in OED (1.61) than control (1.25) and reduced with grade severity. TNOM, type and location were better predictors when combined with histological grading, with the most prognostic models demonstrating an AUROC of 0.81 for transformation and 0.78 for recurrence, exceeding conventional grading. Mitosis quantification and PHH3 staining can be an adjunct to conventional H&E assessment and grading for the prediction of OED prognosis. Validation on larger multicentre cohorts is needed to establish these findings.
Topics: Humans; Histones; Prognosis; Mitotic Index; Biomarkers, Tumor; Neoplasm Grading; Mitosis; Phosphorylation
PubMed: 37882821
DOI: 10.1007/s00428-023-03668-6 -
Polish Journal of Pathology : Official... Jun 2015The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the...
The study represents a comprehensive retrospective morphological and immunohistochemical profiling of pancreatic neuroendocrine neoplasms (PNENs) in order to reveal the associations between morphological and molecular parameters. The local tumour spread (T), presence of metastases in regional lymph nodes (N) and distant organs (M), tumour grade (G) and resection line status (R) by pathology findings (pTNMGR), mitotic activity, perineural, vascular and lymphatic invasion were assessed in 16 surgically resected PNENs. By immunohistochemistry, expression of Ki-67, p53, p27, p21, cyclin D1, Bcl-2, E-cadherin, CD44, vimentin, cyclooxygenase 2 (COX-2), microvascular density, and cytokeratin (CK) spectrum, along with neuroendocrine, intestinal and squamous markers were detected. Descriptive statistics, Chi-square test, Spearman's rank correlation, Mann-Whitney and Kruskal-Wallis methods were applied; p<0.05 was considered significant. Ki-67, CK19, p63, vimentin and COX-2 were significantly up-regulated in PNENs in comparison to benign pancreatic islets. A complex network of morphological and molecular associations was identified. Ki-67 correlated with PNEN size (p=0.022), the World Health Organization 2004 and 2010 classification grades (p=0.021 and p=0.002), stage (p=0.028) and mitotic count (p=0.007) but among molecular markers--with CK19 (p=0.033) and vimentin (p=0.045). CK19 was significantly up-regulated in PNENs, having higher pT (p=0.018), pR (p=0.025), vascular (p=0.020), perineural (p=0.026) and lymphatic invasion (p=0.043). In conclusion, proliferation activity (by Ki-67), E-cadherin, vimentin and CK19 are important molecular characteristics of PNENs due to significant associations with morphological tumour characteristics, pTNMGR and invasive growth.
Topics: Aged; Biomarkers, Tumor; Biopsy; Cell Proliferation; Chi-Square Distribution; Female; Humans; Immunohistochemistry; Lymphatic Metastasis; Male; Middle Aged; Mitotic Index; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Neuroendocrine Tumors; Pancreatic Neoplasms; Predictive Value of Tests; Retrospective Studies; Treatment Outcome
PubMed: 26247532
DOI: 10.5114/pjp.2015.53015 -
Ecotoxicology and Environmental Safety Apr 2021The rampant use of pesticides can cause serious environmental problems. They can be contaminating surface water and groundwater, affecting the surrounding micro and...
The rampant use of pesticides can cause serious environmental problems. They can be contaminating surface water and groundwater, affecting the surrounding micro and macro biota. In this sense, this work aimed to evaluate the effects of a tebuconazole-based fungicide through endpoints accessed in Lactuca sativa bioassays. Germinated-seeds with roots upon 2 mm were treated with a fungicide containing Tebuconazole (TBZ) as active compound. The final concentration of TBZ in the tested solutions were 0.025 (C1); 0.05 (C2); 0.1 (C3); 0.2 (C4) and 0.4 g/L (C5). L. sativa roots were exposed for 24 h to these solutions and Petri dishes containing the treated seeds were kept in incubation chamber at 24 °C. Two positive controls (PC,) the herbicide trifluralin (0.84 mg/L) and Methanesulfonate (4 ×10 mol/L), were applied. Distilled water was negative control (NC). The following endpoints were analyzed: root growth (RG), cytogenotoxic potential by cell cycle analysis, induction of DNA damage through TUNEL and comet assays. The obtained data were submitted to one-way variance analysis (ANOVA) and then to Tukey or Kruskal Wallis (P < 0.05) tests. The concentrations (C1, C2, C4 and C5) affected negatively the RG of L. sativa, in comparison with the NC. The mitotic index was reduced by 25% from NC to C1 and in the rest of treatments it did not present significant modifications. However, from C3 to C5 great amount of chromosome alterations were observed, in comparison with the NC. TBZ-based fungicide also induced DNA fragmentation as measured by TUNEL and comet assays. Thus, TBZ-based fungicide in some concentrations can have phytotoxic, cytotoxic and genotoxic effects in roots and meristematic cells of L. sativa.
Topics: Biological Assay; Chromosome Aberrations; Comet Assay; DNA Damage; Fungicides, Industrial; Germination; Herbicides; Lactuca; Meristem; Mitotic Index; Plant Roots; Seeds; Toxicogenetics; Triazoles
PubMed: 33578099
DOI: 10.1016/j.ecoenv.2021.111985 -
Medicine Jan 2017Conditional disease-free survival (CDFS) reflects changes over time. Because traditional disease-free survival (DFS) is estimated from the date of diagnosis, it is...
Conditional disease-free survival (CDFS) reflects changes over time. Because traditional disease-free survival (DFS) is estimated from the date of diagnosis, it is limited in the ability to predict risk of recurrence in patients who have been disease free. In this study, we determined CDFS of breast cancer patients and estimated the prognostic factors for DFS.We retrospectively reviewed clinical data of 7587 consecutive patients who underwent curative surgery for breast cancer between January 2004 and December 2013 at Samsung Medical Center. Univariate and multivariate analyses were performed to identify risk factors for DFS, which was computed using the Kaplan-Meier method. CDFS rates were based on cumulative DFS estimates.Median follow-up duration was 20.59 months. Three-year DFS was 93.46% at baseline. Three-year CDFS survival estimates for patients who had been disease free for 1, 2, 3, 4, and 5 years after treatment were calculated as 92.84%, 92.37%, 93.03%, 89.41%, and 79.64%, respectively. Three-year CDFS increased continuously each year after 1 year of DFS in hormone receptor (HR)-negative patients but decreased each year in HR-positive patients.In HR-positive patients who are disease free after 3 years, continuous care including surveillance and metastases workup should be considered, although this is not recommended in the current guidelines. On the other hand, the social costs may be reduced in HR-negative patients by extending the surveillance interval. Further studies are needed to identify indicators of DFS prognosis in breast cancer patients.
Topics: Blood Vessels; Breast Neoplasms; Carcinoma, Ductal, Breast; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Lymphatic Metastasis; Lymphatic Vessels; Middle Aged; Mitotic Index; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Time Factors
PubMed: 28072715
DOI: 10.1097/MD.0000000000005746 -
Polish Archives of Internal Medicine Jun 2018Introduction Adrenocortical carcinoma (ACC) is a rare malignancy, associated with poor outcome and few therapeutic options. Despite increasing attention, the knowledge...
Introduction Adrenocortical carcinoma (ACC) is a rare malignancy, associated with poor outcome and few therapeutic options. Despite increasing attention, the knowledge about the clinical course and treatment of these tumors is limited. Objectives Survival rates in ACC are still low and the percentage of relapse is high. Thus, it is crucial to identify the prognostic factors of overall survival (OS) and recurrence‑free survival (RFS). Patients and methods This was a retrospective analysis of 66 patients diagnosed with ACC between 2002 and 2015. Results The median OS was 43.5 months, 78.19 months for stage I + II, 22.95 months for stage III, and 19.54 months for stage IV ACC. Older age, stage IV ACC, margin status R2, and no mitotane treatment were associated with poor OS. Low Ki67 and mitotic indices were related to improved OS in a univariate analysis. The median RFS was 101.1 months. Disease recurrence after potentially curative surgery was reported in 1 patient (25%) with stage I, 12 patients (46%) with stage II, and 9 patients (45%) with stage III ACC. Male sex and no mitotane treatment were associated with a reduced RFS in a multivariate analysis and higher Ki67 and mitotic indices in the univariate analysis. Conclusions Ki67 and mitotic indices should be considered as prognostic factors when planning the adjuvant treatment of ACC. Mitotane treatment may be independently associated with better outcomes regardless of the tumor stage.
Topics: Adrenocortical Carcinoma; Adult; Aged; Female; Humans; Male; Middle Aged; Mitotane; Mitotic Index; Poland; Prognosis; Retrospective Studies; Survival Rate
PubMed: 29726479
DOI: 10.20452/pamw.4260 -
Biochimica Et Biophysica Acta May 2015Cancer cells with defective DNA decatenation checkpoint can be selectively targeted by the catalytic inhibitors of DNA topoisomerase IIα (topo IIα) enzyme. Upon...
Cancer cells with defective DNA decatenation checkpoint can be selectively targeted by the catalytic inhibitors of DNA topoisomerase IIα (topo IIα) enzyme. Upon treatment with catalytic topo IIα inhibitors, cells with defective decatenation checkpoint fail to arrest their cell cycle in G2 phase and enter into M phase with catenated and under-condensed chromosomes resulting into impaired mitosis and eventually cell death. In the present work we analyzed decatenation checkpoint in five different colon cancer cell lines (HCT116, HT-29, Caco2, COLO 205 and SW480) and in one non-cancerous cell line (HEK293T). Four out of the five colon cancer cell lines i.e. HCT116, HT-29, Caco2, and COLO 205 were found to be compromised for the decatenation checkpoint function at different extents, whereas SW480 and HEK293T cell lines were found to be proficient for the checkpoint function. Upon treatment with ICRF193, decatenation checkpoint defective cell lines failed to arrest the cell cycle in G2 phase and entered into M phase without proper chromosomal decatenation, resulting into the formation of tangled mass of catenated and under-condensed chromosomes. Such cells underwent mitotic catastrophe and rapid apoptosis like cell death and showed higher sensitivity for ICRF193. Our study suggests that catalytic inhibitors of topoisomerase IIα are promising therapeutic agents for the treatment of colon cancers with defective DNA decatenation checkpoint.
Topics: Biocatalysis; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Cell Survival; Chromosomes, Human; Colonic Neoplasms; Diketopiperazines; Etoposide; G2 Phase; HEK293 Cells; Humans; Mitosis; Mitotic Index; Piperazines; Topoisomerase II Inhibitors; Tumor Stem Cell Assay
PubMed: 25746763
DOI: 10.1016/j.bbamcr.2015.02.021 -
Oncotarget Jul 2017Background Due to the extremely rare incidence, data of clinicopathological features and prognosis of mesenteric gastrointestinal stromal tumors (GISTs) are limited....
Background Due to the extremely rare incidence, data of clinicopathological features and prognosis of mesenteric gastrointestinal stromal tumors (GISTs) are limited. Therefore, the aim of the present study was to investigate the clinicopathological features and prognosis of mesenteric GISTs.Patients and Methods Mesenteric GISTs cases were obtained from our center and from case reports and clinical series extracted from MEDLINE. Clinicopathological features and survivals were analyzed.Results A total of 114 mesenteric GISTs were enrolled in present study. The most common symptom was abdominal pain (20/72, 27.8%), followed by abdominal mass (13/72, 18.1%) and distention (9/72, 12.5%). Most tumors exceeded 10 cm in diameter (71/112, 63.4%), exceeded 5/50HPF in mitotic index (50/85, 58.8%), and were high risk (82/90, 91.1%). The five-year disease free survival (DFS) and disease specific survival (DSS) was 57.7% and 60.1%, respectively. Tumor size and mitotic index were associated with DFS and DSS. The distribution of tumor size, histological type, mitotic index and NIH risk category were significantly different between mesenteric and gastric GISTs. Prognosis of mesenteric GISTs was worse than that of gastric GISTs. However, multivariate analysis showed that location was not an independent prognostic factor for mesenteric and gastric GISTs.Conclusions Most mesenteric GISTs exceeded 10 cm in diameter, exceeded 5/50HPF in mitotic index and were high risk. Mesenteric GISTs differed significantly from gastric GISTs in respect to clinicopathologic features. Mitotic index and tumor size were prognostic factors for mesenteric GISTs. The prognosis were comparable between mesenteric and gastric GISTs.
Topics: Adult; Aged; Biomarkers, Tumor; Female; Gastrointestinal Stromal Tumors; Humans; Male; Mesentery; Middle Aged; Mitotic Index; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Survival Analysis; Tumor Burden
PubMed: 28147326
DOI: 10.18632/oncotarget.14880 -
The American Journal of Surgical... Dec 2017Solitary fibrous tumors (SFTs) of the head and neck are uncommon. Lesions previously diagnosed in the head and neck as hemangiopericytomas (HPCs), giant cell...
Solitary fibrous tumors (SFTs) of the head and neck are uncommon. Lesions previously diagnosed in the head and neck as hemangiopericytomas (HPCs), giant cell angiofibromas (GCAs), and orbital fibrous histiocytomas (OFHs) are now recognized as within the expanded spectrum of SFTs. To better understand the clinicopathologic profile of head and neck SFTs, we performed a multi-institutional study of 88 examples. There was no sex predilection (F:M ratio 1.2), and the median patient age was 52 years (range: 15 to above 89 y). The sinonasal tract and orbit were the most common sites involved (30% and 25%), followed by the oral cavity and salivary glands (15% and 14%). Original diagnoses included HPC (25%), SFT (67%), and OFH (6%), with 1 SFT and 1 OFH noted as showing GCA-like morphology. On review, the predominant histologic pattern was classic SFT-like in 53% and cellular (former HPC-like) in 47%; lipomatous differentiation (8%) and GCA-like pattern (7%) were less prevalent. Subsets demonstrated nuclear atypia (23%), epithelioid morphology (15%), or coagulative necrosis (6%). Infiltrative growth (49%) and osseous invasion (82%) were prevalent among evaluable cases. Of the 48 SFTs with follow-up (median: 43 mo), 19 showed recurrence (40%). Of these, 4 patients were alive with disease and 4 dead of disease. Size and mitotic rate were negative prognosticators using a joint prognostic proportional hazards regression model. Three patients experienced metastasis, to lungs, parotid, bone, and skull base, including one case showing overtly sarcomatous "dedifferentiation." As a group, SFTs present in a wide anatomic and morphologic spectrum in the head and neck. Only rare examples metastasize or cause death from disease. However, the fairly high local recurrence rate underscores their aggressive potential and highlights the importance of prospective recognition.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Proliferation; Disease Progression; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Mitotic Index; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Proportional Hazards Models; Retrospective Studies; Risk Factors; Solitary Fibrous Tumors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; United States; Young Adult
PubMed: 28877055
DOI: 10.1097/PAS.0000000000000940 -
BMC Gastroenterology Nov 2014Serotonin exhibits a vast repertoire of actions including cell proliferation and differentiation. The effect of serotonin, as an incomplete mitogen, on liver...
BACKGROUND
Serotonin exhibits a vast repertoire of actions including cell proliferation and differentiation. The effect of serotonin, as an incomplete mitogen, on liver regeneration has recently been unveiled and is mediated through 5-HT2 receptor. The aim of the present study was to investigate the effect of 5-HT7 receptor blockade on liver regeneration after partial hepatectomy.
METHODS
Male Wistar rats were subjected to 60-70% partial hepatectomy. 5-HT7 receptor blockade was applied by intraperitoneal administration of SB-269970 hydrochloride two hours prior to and sixteen hours after partial hepatectomy and by intraperitoneal administration of SB-258719 sixteen hours after partial hepatectomy. Animals were sacrificed at different time points until 72 h after partial hepatectomy. Liver regeneration was evaluated by [(3)H]-thymidine incorporation into hepatic DNA, the mitotic index in hematoxylin-eosin (HE) sections and by immunochemical detection of Ki67 nuclear antigen. Reversion of 5-HT7 blockade was performed by intraperitoneal administration of AS-19. Serum and liver tissue lipids were also quantified.
RESULTS
Liver regeneration peaked at 24 h ([(3)H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and at 32 h (mitotic index in HE sections) in the control group of rats. 5-HT7 receptor blockade had no effect on liver regeneration when applied 2 h prior to partial hepatectomy. Liver regeneration was greatly attenuated when blockade of 5-HT7 receptor was applied (by SB-258719 and SB-269970) at 16 h after partial hepatectomy and peaked at 32 h ([(3)H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and 40 h (mitotic index in HE sections) after partial hepatectomy. AS-19 administration totally reversed the observed attenuation of liver regeneration.
CONCLUSIONS
In conclusion, 5-HT7 receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation.
Topics: Animals; Cell Proliferation; DNA; Dose-Response Relationship, Drug; Hepatectomy; Hepatocytes; Lipid Metabolism; Lipids; Liver; Liver Regeneration; Male; Phenols; Piperidines; Rats, Wistar; Receptors, Serotonin; Serotonin Antagonists; Sulfonamides; Thymidine
PubMed: 25433672
DOI: 10.1186/s12876-014-0201-2