molecular profile
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Author(s):  
Antonio Travaglino ◽  
Antonio Raffone ◽  
Diego Raimondo ◽  
Sabrina Reppuccia ◽  
Alessandro Ruggiero ◽  
...  

Abstract Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 420
Author(s):  
Paola Vignali ◽  
Agnese Proietti ◽  
Elisabetta Macerola ◽  
Anello Marcello Poma ◽  
Liborio Torregrossa ◽  
...  

Background: Non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were introduced in thyroid pathology in 2016. NIFTPs are a group of follicular neoplasm with an indolent behaviour. In this study, we gathered a large retrospective cohort of NIFTPs and compared those presenting as solitary lesions and NIFTPs found in multifocal setting. Methods: A retrospective search of NIFTPs was performed, and the clinico-pathological features were recorded. For a subgroup of patients, pre-surgical ultrasound (US) evaluation, cytological diagnosis, and molecular analysis were available. Results: We collected 451 NIFTPs; 254 (56.3%) were truly solitary tumours, while 197 coexisted with one or more NIFTP/cancer. Contrasting unifocal and multifocal settings, NIFTPs size was the only significantly different parameter. Preoperatively, NIFTP nodules mostly showed low-risk US characteristics, indeterminate cytology and a RAS-like molecular profile. Conclusion: NIFTPs often coexist with collateral thyroid tumours. However, no clinical-pathological differences can be observed between solitary and “multifocal” NIFTPs. Despite the well-established clinical indolence of NIFTP, a careful monitoring of the contralateral lobe should not be excluded.


Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 103
Author(s):  
Minhian Chai ◽  
Muhammad Zikree Sukiman ◽  
Amirah Huda Kamarun Baharin ◽  
Insyirah Ramlan ◽  
Lennard Zhunhoong Lai ◽  
...  

Staphylococcus aureus (S. aureus) infections, particularly methicillin-resistant Staphylococcus aureus (MRSA) in humans and animals, have become a significant concern globally. The present study aimed to determine the prevalence and antibiogram of S. aureus isolated from animal handlers in Peninsular Malaysia. Furthermore, the genotypic characteristics of S. aureus isolates were also investigated. Nasal and oral swab samples were collected from 423 animal handlers in Peninsular Malaysia. The antibiogram profiles of S. aureus against 18 antibiotics were established using a Kirby–Bauer test. The genotypic profile of S. aureus, including the presence of antimicrobial resistance (AMR), virulence genes and spa genotypes, was investigated using molecular techniques. The overall carriage rate of S. aureus, MRSA and MDRSA was 30.5%, 1.2% and 19.4%, respectively. S. aureus was highly resistant against penicillin (72.3%) and amoxicillin (52.3%). Meanwhile, gentamicin and linezolid were fully effective against all the isolated S. aureus from animal handlers. It was observed that animal handlers with close exposure to poultry were more likely to carry S. aureus that is resistant to tetracycline and erythromycin. S. aureus isolates harboured tetracycline resistance (tetK, tetL and tetM), erythromycin resistance (ermA, ermB, ermC and msrA) and immune evasion cluster (IEC) genes (scn, chp, sak, sea and sep). Seventeen different spa types were detected among the 30 isolates of MDRSA, with t189 (16.7%) and t4171 (16.7%) being the predominant spa type, suggesting wide genetic diversity of the MDRSA isolates. The present study demonstrated the prevalence of S. aureus strains, including MRSA and MDRSA with various antimicrobial resistance and genetic profiles from animal handlers in Peninsular Malaysia.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 416
Author(s):  
Martin Köbel ◽  
Eun Young Kang

The phenotypically informed histotype classification remains the mainstay of ovarian carcinoma subclassification. Histotypes of ovarian epithelial neoplasms have evolved with each edition of the WHO Classification of Female Genital Tumours. The current fifth edition (2020) lists five principal histotypes: high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), mucinous carcinoma (MC), endometrioid carcinoma (EC) and clear cell carcinoma (CCC). Since histotypes arise from different cells of origin, cell lineage-specific diagnostic immunohistochemical markers and histotype-specific oncogenic alterations can confirm the morphological diagnosis. A four-marker immunohistochemical panel (WT1/p53/napsin A/PR) can distinguish the five principal histotypes with high accuracy, and additional immunohistochemical markers can be used depending on the diagnostic considerations. Histotypes are further stratified into molecular subtypes and assessed with predictive biomarker tests. HGSCs have recently been subclassified based on mechanisms of chromosomal instability, mRNA expression profiles or individual candidate biomarkers. ECs are composed of the same molecular subtypes (POLE-mutated/mismatch repair-deficient/no specific molecular profile/p53-abnormal) with the same prognostic stratification as their endometrial counterparts. Although methylation analyses and gene expression and sequencing showed at least two clusters, the molecular subtypes of CCCs remain largely elusive to date. Mutational and immunohistochemical data on LGSC have suggested five molecular subtypes with prognostic differences. While our understanding of the molecular composition of ovarian carcinomas has significantly advanced and continues to evolve, the need for treatment options suitable for these alterations is becoming more obvious. Further preclinical studies using histotype-defined and molecular subtype-characterized model systems are needed to expand the therapeutic spectrum for women diagnosed with ovarian carcinomas.


2022 ◽  
Vol 20 (6) ◽  
pp. 55-68
Author(s):  
D. E. Matsko ◽  
M. V. Matsko ◽  
A. O. Baksheeva ◽  
E. N. Imyanitov ◽  
A. Yu. Ulitin ◽  
...  

Introduction. Intratumor heterogeneity is one of the key reasons for unfavourable prognosis in malignant tumors. Astrocytic tumors are known to develop therapy resistance inevitably during the course of disease. One of possible reason is tumor heterogeneity. Purpose. The aim of this work was to assess the intratumor morphologic and molecular heterogeneity in diffuse astrocytoma, anaplastic astrocytomas and primary glioblastomas. Material and methods. We conducted morphologic (n=22) and molecular-genetic (n=8) analysis of surgical specimens obtained from primarily operated glioblastoma giv (gb), anaplastic astrocytomas giii (aa) and diffuse astrocytoma gii (da) patients aged 18 years and older in whom total or subtotal tumor resection was performed. Tissue sampling for the analysis was performed from 5 equidistant areas of each tumor. Morphologic diagnosis was established according to who classification of central nervous system tumors (2007/2016). Mgmt, c-kit, top2a, pdgfr-α, ercc1, vegf genes mrnaexpression was assessed by rt-pcr. Idh1 and idh2 mutational status was evaluated by allele-specific pcr. Results. Morphologic heterogeneity was evident in 72,7 % tumors (16/22) overall. Heterogeneity was observed in 68,8 % (11/16) of gb, 80 % (4/5) of aa and in the only case of da. In 50 % of cases at least 3 different morphologic variants were seen in different areas of the tumor. This morphologic heterogeneity presented as the combination of different grades of anaplasia (gii – giv) in one tumor. Molecular profile was assessed in 48 expression analysis of genes: mgmt, c-kit, top2a, pdgfr-α, ercc1, vegf from 8 patients. Intratumoral molecular heterogeneity was revealed in 41,7 % of cases (20/48). Conclusion. The presence of intratumoral heterogeneity should be taken into account during surgery for adequate tumor sampling for histologic and molecular analysis which is critical for proper assessment of prognosis and following treatment planning.


2022 ◽  
Author(s):  
Federico Cucchiara ◽  
Rosa Scarpitta ◽  
Stefania Crucitta ◽  
Cristian Scatena ◽  
Roberta Arici ◽  
...  

Imaging and tissue biopsies represent the current gold standard for breast cancer diagnosis and patient management. However, these practices are time-consuming, expensive and require invasive procedures. Moreover, tissue biopsies do not capture spatial and temporal tumor heterogeneity. Conversely, liquid biopsy, which includes circulating tumor cells, circulating free nucleic acids and extracellular vesicles, is minimally invasive, easy to perform and can be repeated during a patient's follow-up. Increasing evidence also suggests that liquid biopsy can be used to efficiently screen and diagnose tumors at an early stage, and to monitor changes in the tumor molecular profile. In the present review, clinical applications and prospects are discussed.


2022 ◽  
pp. 1-11
Author(s):  
Aditi Bhatt ◽  
Olivier Glehen

<b><i>Background:</i></b> Advanced epithelial ovarian cancer (EOC) is an incurable disease with over 75% of the patients developing recurrence in the peritoneum. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment option for both first-line therapy and treatment of recurrence. In this article, we review the rationale and current evidence for performing HIPEC and the role of HIPEC in the light of targeted systemic therapies. <b><i>Summary:</i></b> There are few randomized trials and several retrospective studies on the role of HIPEC in the management of EOC. A 12-month-overall survival (OS) benefit of the addition of HIPEC to interval cytoreductive surgery (CRS) was demonstrated in 1 randomized trial following which HIPEC has been included as a treatment option for this indication in several national/international guidelines. One retrospective propensity score-matched analysis showed a 16-month OS benefit of adding HIPEC to primary CRS. One randomized trial showed no benefit of the addition of carboplatin HIPEC to secondary CRS over secondary CRS alone. For patients undergoing primary CRS and secondary CRS for recurrence, the results of ongoing randomized trials are needed to define the role of HIPEC in these situations. All clinical trials have shown that the morbidity of HIPEC performed after CRS is acceptable. Along with the emergence of HIPEC as a promising surgical therapy, targeted therapies like bevacizumab and poly adenosine diphosphate-ribose polymerase inhibitors have been developed that have shown a survival benefit in selected patients. In principle, HIPEC and targeted therapies work in different ways and it is plausible to assume that their benefit could be additive, and their combination should be evaluated in clinical trials. The impact of prognostic factors like the disease extent, pathological response to systemic chemotherapy (SC), the histological subtype and molecular profile on the benefit of HIPEC, and targeted therapies has not been evaluated in clinical trials. <b><i>Key Messages:</i></b> HIPEC is an important therapeutic strategy in the treatment of EOC. While its role in patients undergoing interval CRS has been established, the results of ongoing randomized trials are needed to define its benefit at other time points. The morbidity of HIPEC in addition to CRS is acceptable. More research is needed to define subgroups that benefit most from HIPEC based on the extent of disease, response to SC, histology, and molecular profile. The combination of HIPEC and maintenance therapies should be evaluated in well-designed randomized clinical trials that evaluate not just the survival benefit and morbidity but also the cost-effectiveness of each therapy.


2022 ◽  
Vol 23 (2) ◽  
pp. 705
Author(s):  
Lavinia Raimondi ◽  
Alessia Gallo ◽  
Nicola Cuscino ◽  
Angela De Luca ◽  
Viviana Costa ◽  
...  

Osteosarcoma (OS) is the most common primary bone tumor mainly occurring in young adults and derived from primitive bone-forming mesenchyme. OS develops in an intricate tumor microenvironment (TME) where cellular function regulated by microRNAs (miRNAs) may affect communication between OS cells and the surrounding TME. Therefore, miRNAs are considered potential therapeutic targets in cancer and one of the goals of research is to accurately define a specific signature of a miRNAs, which could reflect the phenotype of a particular tumor, such as OS. Through NGS approach, we previously found a specific molecular profile of miRNAs in OS and discovered 8 novel miRNAs. Among these, we deepen our knowledge on the fifth candidate renamed now miR-CT3. MiR-CT3 expression was low in OS cells when compared with human primary osteoblasts and healthy bone. Through TargetScan, VEGF-A was predicted as a potential biological target of miR-CT3 and luciferase assay confirmed it. We showed that enforced expression of miR-CT3 in two OS cell lines, SAOS-2 and MG-63, reduced expression of VEGF-A mRNA and protein, inhibiting tumor angiogenesis. Enforced expression of miR-CT3 also reduced OS cell migration and invasion as confirmed by soft agar colony formation assay. Interestingly, we found that miR-CT3 behaves inducing the activation of p38 MAP kinase pathway and modulating the epithelial-mesenchymal transition (EMT) proteins, in particular reducing Vimentin expression. Overall, our study highlights the novel role of miR-CT3 in regulating tumor angiogenesis and progression in OS cells, linking also to the modulation of EMT proteins.


Author(s):  
Michalis Panteli ◽  
James S.H. Vun ◽  
Ippokratis Pountos ◽  
Anthony Howard ◽  
Elena Jones ◽  
...  

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