-
ESMO Open Jun 2024Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort...
BACKGROUND
Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers.
PATIENTS AND METHODS
Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value.
RESULTS
The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value.
CONCLUSIONS
This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.
Topics: Humans; Lung Neoplasms; Neuroendocrine Tumors; Female; Ki-67 Antigen; Male; Biomarkers, Tumor; Middle Aged; World Health Organization; Histones; Aged; Prognosis; Deep Learning
PubMed: 38878324
DOI: 10.1016/j.esmoop.2024.103591 -
Archives of Microbiology Jun 2024Environmental contamination from petroleum refinery operations has increased due to the rapid population growth and modernization of society, necessitating urgent...
Environmental contamination from petroleum refinery operations has increased due to the rapid population growth and modernization of society, necessitating urgent repair. Microbial remediation of petroleum wastewater by prominent bacterial cultures holds promise in circumventing the issue of petroleum-related pollution. Herein, the bacterial culture was isolated from petroleum-contaminated sludge samples for the valorization of polyaromatic hydrocarbons and biodegradation of petroleum wastewater samples. The bacterial strain was screened and identified as Bacillus subtilis IH-1. After six days of incubation, the bacteria had degraded 25.9% of phenanthrene and 20.3% of naphthalene. The treatment of wastewater samples was assessed using physico-chemical and Fourier-transform infrared spectroscopy analysis, which revealed that the level of pollutants was elevated and above the allowed limits. Following bacterial degradation, the reduction in pollution parameters viz. EC (82.7%), BOD (87.0%), COD (80.0%), total phenols (96.3%), oil and grease (79.7%), TKN (68.8%), TOC (96.3%) and TPH (52.4%) were observed. The reduction in pH and heavy metals were also observed after bacterial treatment. V. mungo was used in the phytotoxicity test, which revealed at 50% wastewater concentration the reduction in biomass (30.3%), root length (87.7%), shoot length (93.9%), and seed germination (30.0%) was observed in comparison to control. When A. cepa root tips immersed in varying concentrations of wastewater samples, the mitotic index significantly decreased, suggesting the induction of cytotoxicity. However, following the bacterial treatment, there was a noticeable decrease in phytotoxicity and cytotoxicity. The bacterial culture produces lignin peroxidase enzyme and has the potential to degrade the toxic pollutants of petroleum wastewater. Therefore the bacterium may be immobilised or directly used at reactor scale or pilot scale study to benefit the industry and environmental safety.
Topics: Bacillus subtilis; Biodegradation, Environmental; Wastewater; Petroleum; Phenanthrenes; Naphthalenes; Water Pollutants, Chemical; Sewage; Metals, Heavy
PubMed: 38856816
DOI: 10.1007/s00203-024-04027-y -
Journal of Immunoassay & Immunochemistry May 2024Now, targeted therapy and immunotherapy are promoted. tumour -Associated Macrophages (TAMs) are an essential component of immune-response in breast cancer(BC) with...
Is overexpression of CD163 and CD47 in tumour cells of breast carcinoma implicated in the recruitment of tumour-associated macrophages (TAMs) in tumour microenvironment? immunohistochemical prognostic study.
BACKGROUND
Now, targeted therapy and immunotherapy are promoted. tumour -Associated Macrophages (TAMs) are an essential component of immune-response in breast cancer(BC) with prognostic controversy. Additionally, their recruiting factors are still obscure. Purpose:This study aimed to evaluate the prognostic significance of CD163 and CD47 in BC of No Special Type (BC-NST) and to explore their suggested role in recruiting TAMs.
MATERIAL AND METHODS
This immunohistochemical study was conducted on 91 archival specimens of breast cases. Immunoreactivity scores were correlated with TAMs density, clinicopathological data, and survival.
RESULTS
Revealed the highest CD163 expression was detected in the pure DCIS group ( = 0.016), while the highest CD47 expression and high TAMs density were reported in the invasive group ( = 0.008, and = 0.002 respectively) followed by the DCIS group. In IC-NSTs the CD163 and CD47 scores were associated with poor prognostic parameters like(high grade, advanced stage, distant metastasis, ER negativity,Ki67 index, post-surgical chemotherapy, poor NPI group, high mitotic count, dense infiltration of TAMs, shorter OS). Also, CD47 was associated with the dens infiltration of TAMs in DCIS ( = 0.001). There was a significant correlation between tumour cell expression of CD163 and CD47 in IC-NSTs and DCIS ( = 0.002 and = 0.009 respectively).
CONCLUSIONS
High CD163 and CD47 expressions in both DCIS andIBC are intimately associated, significantly associated with poor prognosis and are important provoking factors of TAMs.
PubMed: 38815282
DOI: 10.1080/15321819.2024.2358879 -
Annals of Clinical and Laboratory... Mar 2024Meningioma is the most common primary adult intracranial neoplasm, and proliferation indices (PI) rise with increasing grade from WHO CNS grade 1 to 3. Ki-67... (Review)
Review
OBJECTIVE
Meningioma is the most common primary adult intracranial neoplasm, and proliferation indices (PI) rise with increasing grade from WHO CNS grade 1 to 3. Ki-67 immunohistochemistry (IHC) poses a variety of technical and interpretative challenges. Here, we specifically investigated the staining intensity and its effect on interpretation and final diagnosis.
METHODS
124 high and low-grade meningiomas of various grades were blindly evaluated using different counting strategies (CS) based on the staining intensity of the nuclei as darkest (CS1), darkest+intermediate (CS2), and any staining (CS3) in hot-spots (HS) and in the context of overall proliferative activity (OPA).
RESULT
CSs in HS, OPA, and their average results were significantly different between low-grade and high-grade groups. PI obtained using CS3 yielded results that matched best with values expected for the corresponding WHO grade. CS had a profound impact on whether a LG meningioma would be diagnosed as one with a "high proliferation index."
CONCLUSION
A large body of work exists on the counting methods, clinically significant cut-off values, and inter- and intra-observer variability for Ki-67 PI interpretation. We show that Ki-67 IHC staining intensity, which to our knowledge has not been previously systematically investigated, can have a significant effect on PI interpretation in settings that influence diagnostic and clinical management decisions.
Topics: Humans; Meningioma; Ki-67 Antigen; Cell Proliferation; Meningeal Neoplasms; Immunohistochemistry; Neoplasm Grading; Female; Staining and Labeling; Male; Middle Aged; Aged; Adult; Mitotic Index
PubMed: 38802155
DOI: No ID Found -
Histochemistry and Cell Biology May 2024Hyperthermia along with hydrocortisone (HC) are proven teratogens that can negatively influence embryo development during early pregnancy. Proliferation of cells is one...
Hyperthermia along with hydrocortisone (HC) are proven teratogens that can negatively influence embryo development during early pregnancy. Proliferation of cells is one of the main developmental processes during the early embryogenesis. This study was focused on testing the effect of elevated temperature and HC addition on proliferation of cells in in vitro cultures. The V79-4 cell line was treated with HC and cultured in vitro at 37 °C or 39 °C, respectively. To reveal the effect of both factors, the proliferation of cells cultured under different conditions was evaluated using various approaches (colony formation assay, generation of growth curves, computation of doubling times, and mitotic index estimation). Our results indicate that a short-term exposure to elevated temperature slightly stimulates and a long-term exposure suppresses cell proliferation. However, HC (0.1 mg/ml) acts as a stimulator of cell proliferation. Interestingly, the interaction of HC and long-term elevated temperature (39 °C) exposure results in at least partial compensation of the negative impact of elevated temperature by HC addition and in higher proliferation if compared with cells cultured at 39 °C without addition of HC.
PubMed: 38801536
DOI: 10.1007/s00418-024-02295-9 -
Problemy Endokrinologii Oct 2023Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and... (Review)
Review
Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and «non-metastatic». Metastatic PPGLs can be with synchronous metastasis (metastases appear simultaneously with the identified primary tumor) or metachronous (metastases develop after removal of the primary tumor). The term metastatic PPGLs is not used in the presence of tumor invasion into surrounding organs and tissues, without the presence of distant metastases of lymphogenic or hematogenic origin. It is generally believed that about 10% of pheochromocytomas and about 40% of sympathetic paragangliomas have metastatic potential. On average, the prevalence of PPGLs with the presence of metastases is 15-20%. Risk factors for metastatic PPGLs are widely discussed in the literature, the most significant of which are groups of clinical, morphological and genetic characteristics. The review presents a discussion of such risk factors for metastatic PPGLs as age, localization and type of hormonal secretion of the tumor, the size and growth pattern of the adrenal lesion, the presence of necrosis and invasion into the vessels, the tumor capsule surrounding adipose tissue, high cellular and mitotic activity, Ki-67 index, expression of chromogranin B and S100 protein, the presence of genetic mutations of three main clusters (pseudohypoxia, kinase signaling and Wnt signaling).Over the past two decades, a number of authors have proposed various predictor factors and scales for assessing a probability of metastatic PPGLs. The review contains detailed description and comparison of sensitivity and specificity of such predictor scales as PASS, GAPP, M-GAPP, ASES and COPPS.
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms; Risk Factors; Paraganglioma; Neoplasm Metastasis
PubMed: 38796759
DOI: 10.14341/probl13331 -
Research in Veterinary Science Jul 2024Myxosarcoma is a rare malignant mesenchymal neoplasm of soft tissues originating from fibroblasts. This report describes a case of bilateral myxosarcoma in a...
Myxosarcoma is a rare malignant mesenchymal neoplasm of soft tissues originating from fibroblasts. This report describes a case of bilateral myxosarcoma in a three-year-old cryptorchid dog. The animal was referred to the veterinary clinic because of the absence of testicles in the scrotum. Ultrasonography revealed two masses in the abdominal cavity with testicular echotexture. Exploratory laparotomy revealed the presence of cryptorchid testicles, and orchiectomy was recommended to treat the animal. Testicles were gray and reddish in color and enlarged with firm consistency. For histopathological analysis, testis fragments were fixed in 10% formalin and stained with hematoxylin and eosin and Alcian blue. Immunohistochemistry was performed using the following primary antibodies:1A4, HHF35, desmin, glial fibrillary acidic protein, CD31, S-100, vimentin, and Ki-67. Histopathological evaluation revealed the proliferation of fusiform and round cells associated with extensive areas of myxoid matrix. Neoplasms featured multinucleated giant cells, pleomorphism, karyomegaly, nuclear hyperchromasia, anisokaryosis, mitoses, and necrosis, with coarse chromatin and prominent nucleoli. Immunohistochemical analysis of vimentin- and the Alcian blue-positive cells confirmed the diagnosis of myxosarcoma. A high mitotic count and Ki-67 proliferative index suggests this myxosarcoma had a high degree of malignancy. To the best of our knowledge, this is the first case report of bilateral testicular myxosarcoma in a cryptorchid animal.
Topics: Male; Animals; Dogs; Dog Diseases; Testicular Neoplasms; Myxosarcoma; Cryptorchidism; Orchiectomy; Immunohistochemistry
PubMed: 38788298
DOI: 10.1016/j.rvsc.2024.105308 -
International Journal of Radiation... 2024To analyze the effects of extending lymphocyte cultivation time on the Mitotic Index, frequency of first-division cells, and dose estimation after irradiating blood...
PURPOSE
To analyze the effects of extending lymphocyte cultivation time on the Mitotic Index, frequency of first-division cells, and dose estimation after irradiating blood samples with different doses of radiation.
MATERIALS AND METHODS
Blood samples from two healthy male volunteers were separately irradiated with three doses (3, 5, and 6 Gy) using a Co gamma source (average dose rate: 1.48 kGy.h) and cultivated for conventional (48 h) and extended (56, 68, and 72 h) amounts of time. Colcemid (0.01 µg.mL) was added at the beginning of the culture period. Cells were fixed, stained with (FPG), and analyzed under a light microscope. The effects of prolonged culture duration on the Mitotic Index (MI), frequency of first-division cells (M1 cells), and the First-Division Mitotic Index (FDMI) were investigated. The estimation of delivered doses was conducted using a conventional 48h-culture calibration curve.
RESULTS
Overall, cells presented higher MI (up to 12-fold) with the extension of culture, while higher radiation doses led to lower MI values (up to 80% reduction at 48 h). Cells irradiated with higher doses (5 and 6 Gy) had the most significant increase (5- to 12-fold) of MI as the cultivation was prolonged. The frequency of M cells decreased with the prolongation of culture for all doses (up to 75% reduction), while irradiated cells presented higher frequencies of M cells than non-irradiated ones. FDMI increased for all irradiated cultures but most markedly in those irradiated with higher doses (up to 10-fold). The conventional 48h-culture calibration curve proved adequate for assessing the delivered dose based on dicentric frequency following a 72-hour culture.
CONCLUSION
Compared to the conventional 48-hour protocol, extending the culture length to 72 hours significantly increased the Mitotic Index and the number of first-division metaphases of irradiated lymphocytes, providing slides with a better scorable metaphase density. Extending the culture time to 72 hours, combined with FPG staining to score exclusively first-division metaphases, improved the counting of dicentric chromosomes. The methodology presented and discussed in this study can be a powerful tool for dicentric-based biodosimetry, especially when exposure to high radiation doses is involved.
Topics: Humans; Mitotic Index; Male; Radiometry; Dose-Response Relationship, Radiation; Lymphocytes; Cytogenetic Analysis; Adult; Time Factors; Radiation Dosage; Cells, Cultured; Cell Culture Techniques
PubMed: 38787719
DOI: 10.1080/09553002.2024.2356545 -
Veterinary Sciences May 2024Twelve dogs with oral malignant melanomas (MM) were evaluated in this study, with demographic details indicating a balanced distribution of gender, age, and weight among...
Twelve dogs with oral malignant melanomas (MM) were evaluated in this study, with demographic details indicating a balanced distribution of gender, age, and weight among various breeds. Tumor locations varied, with diverse surgical procedures being performed, including mandibulectomies and maxillectomies. Lymphadenectomies were conducted, revealing a 16.66% metastatic rate in regional lymph nodes. At the time of surgery, clinical staging identified stages I, II, and III, with most cases having non-infiltrated margins and a high mitotic index. Follow-up revealed local recurrences and metastases, prompting additional surgeries and affecting survival rates. This study reports varying outcomes, with some dogs completing one year without recurrence, while others experienced progressive disease, leading to six oral melanoma-related deaths. The characteristics of melanotic melanoma and amelanotic melanoma are observed in order to study differences between them, the degree of aggressiveness, the mortality rate and the possibility of future therapeutic targets. Although high pigmentation has been correlated with a better outcome, we could not find any significant correlation between survival and achromia. Oral benign melanomas might exist, and this could justify variabilities between stage and survival; however, carefulness is required due to their unpredictable behavior. The findings underscore the complexity of oral melanoma cases and highlight the need for further research on effective management strategies.
PubMed: 38787198
DOI: 10.3390/vetsci11050226 -
Heliyon May 2024DNA methylation is one of induced changes under salinity stress causing reduction in the expression of several crucial genes required for normal plant's operation....
Exogenous application of 5-azacitidin, royal jelly and folic acid regulate plant redox state, expression level of DNA methyltransferases and alleviate adverse effects of salinity stress on L. plants.
DNA methylation is one of induced changes under salinity stress causing reduction in the expression of several crucial genes required for normal plant's operation. Potential use of royal jelly (RJ), folic acid (FA) and 5-azacitidine (5-AZA) on two Egyptian faba bean varieties (Sakha-3 and Giza-716) grown under saline conditions was investigated. Salinity stress affects negatively on seeds germination (G %), mitotic index, membrane stability and induced a significant increase in chromosomal abnormalities (CAs). DNA methyltransferases genes ( and ) were highly up-regulated (∼23 and 8 folds for and in shoots of Giza-716 stressed plants). On the other hand, down regulation of other studied stress related genes: superoxide dismutase (), catalase ), glutathione reductase (), heat shock protein () and proline-rich protein () were detected in stressed plants of both studied varieties. Treating plants with RJ and FA increase G%, chlorophyll content, improves membrane properties and reduces CAs compared to non-treated stressed plants. Exogenous application of 5-AZA, RJ and FA on salinity stressed plants was associated with a significant reduction in the transcription of and which was associated with significant up regulation in the expression of , , , and encoding genes. The Lowest expression of and were induced with 5-AZA treatment in both studied varieties. Exogenous application of the FA, RJ and 5-AZA modified the methylation state of stressed plants by regulation the expression of DNA methyltransferases, subsequently, modulated the expression of studied genes and could be proposed as a promising treatment to ameliorate hazardous effects of salt stress on different plants.
PubMed: 38784551
DOI: 10.1016/j.heliyon.2024.e30934