Regulatory T (Treg) cells, which are broadly classified as thymically derived (tTreg) or extrathymically induced (iTreg), suppress immune responses and display stringent dependence to the ...transcription factor Foxp3. However precise understanding of molecular events that promote and preserve Foxp3 expression in Treg cells is still evolving. Here we show that Foxp1, a forkhead transcription factor and a sibling family member of Foxp3, is essential for sustaining optimal expression of Foxp3 specifically in iTreg cells. Deletion of Foxp1 renders iTreg cells to gradually lose Foxp3, resulting in dramatically reduced Nrp1
Helios
iTreg compartment as well as augmented intestinal inflammation in aged mice. Our finding underscores a mechanistic module in which evolutionarily related transcription factors establish a molecular program to ensure efficient immune homeostasis. Furthermore, it provides a novel target that can be potentially modulated to exclusively reinforce iTreg stability keeping their thymic counterpart unperturbed.
Background
This study aimed to identify the yield of staging laparoscopy with peritoneal lavage cytology for gastric cancer patients and to track it over time.
Methods
The medical records of patients ...with gastric or gastroesophageal adenocarcinoma who underwent pretreatment staging laparoscopy at the authors’ institution from 1995 to 2012 were reviewed. The yield of laparoscopy was defined as the proportion of patients who had positive findings on laparoscopy, including those with macroscopic carcinomatosis, positive cytology, or other clinically important findings. To compare the yield of laparoscopy over time, the patients were divided into three 6-year ranges based on the date of diagnosis. Associations between clinicopathologic factors and peritoneal disease were examined using uni- and multivariate analyses.
Results
The study included 711 patients. Among these patients, 43.5 % had gastroesophageal junction tumors, 72.9 % had poorly differentiated adenocarcinoma, and 53 % had signet ring cell morphology. Endoscopic ultrasound had most commonly identified T3 (83.9 %) and N-positive (66.4 %) tumors. At laparoscopy, 148 (20.8 %) patients had been found to have macroscopic peritoneal carcinomatosis. Among 514 macroscopically negative patients who underwent peritoneal lavage cytologic analysis, 68 (13.2 %) had positive cytology results for malignancy. The total laparoscopy yield was 36 %, which did not change over time (
p
= 0.58). Multivariate analysis demonstrated that positive cytology or carcinomatosis was associated with poorly differentiated histology, linitis plastica, and equivocal computed tomography findings.
Conclusions
Laparoscopy remains a useful staging procedure to evaluate for peritoneal spread when treatment or surgery is considered, even with the current availability of high-quality imaging.
Objective
Interest in immune therapies has exploded since the 2014 approval of first‐generation programmed cell death 1 blocking antibodies for use in advanced melanoma. Clinical trials have focused ...primarily on histological material as the gold standard for evaluating programmed death ligand 1 (PD‐L1) by immunoperoxidase (IPOX) studies. Studies validating the use of cytological specimens in the assessment of PD‐L1 by IPOX staining are needed to optimise tissue utilisation in complementary diagnostic testing.
Methods
Twenty‐three melanoma surgical biopsies (SBx) with an IPOX stain for PD‐L1 clone 28‐8, and a corresponding cytological specimen from the same patient, adequate for PD‐L1 evaluation, were selected. Cell‐transfer cell blocks (CBs) and conventional CBs were used to perform PD‐L1 testing. Tumour proportion scores (TPS) were generated and the results were correlated with the corresponding SBx.
Results
Overall agreement (OA) using a ≥1% TPS cut‐off for SBx compared to CB was 88.9%, positive percent agreement (PPA) was 87.5%, and negative percent agreement (NPA) was 100%, OA using a ≥5% TPS cut‐off was 55.6%, PPA was 42.9%, and NPA was 100%. SBx compared to cell‐transfer CB using a ≥1% TPS cut‐off had an OA of 65.2%, a PPA of 55.6%, and a NPA of 100%, while a ≥5% TPS cut‐off generated an OA of 52.2%, a PPA of 35.7%, and a NPA of 77.8%.
Conclusion
Our results demonstrate that cytological material, particularly conventional CB, is a viable alternative for evaluating PD‐L1 in melanoma cases and suggest that a lower threshold (≥1%) may be beneficial when evaluating cytological material.
Studies looking at PD‐L1 expression in cytologic material are limited and most of the current literature examines staining in non‐small cell lung carcinoma (NSCLC) patients. In this study we evaluate PD‐L1 28‐8 immunoperoxidase in cytologic specimen preparations in melanoma patients, including conventional cell blocks and cell‐transfer cell blocks, and compare the expression to histologic tissue from the same patient. To the best of our knowledge, this is the first study examining PD‐L1 expression in various cytologic tissues exclusively in melanoma patients.
There has been a paradigm shift in the practice of cytopathology with the advent of highly sensitive molecular tests using small amounts of tissue that can provide diagnostic, prognostic, and ...predictive information for clinical management. The cytopathologist plays a key role in providing a timely and accurate diagnosis as well as ensuring appropriate processing and handling of the specimen and judicious triaging of the tissue for molecular testing that guide therapeutic decisions. As the era of "precision medicine" continues to evolve and expand, cytopathology remains a dynamic field with advances in the practice of molecular cytopathology providing new paradigms in clinical care.
Minimally invasive procedures, such as fine needle aspiration and core needle biopsy, are commonly used for the diagnosis in solid organ malignancies. In the era of targeted therapy, it is crucial ...for molecular testing to be performed on these limited volume specimens. Although several recent studies have demonstrated the utility of small biopsy specimens for molecular testing, there remains debate as to whether core needle biopsy specimens are more reliable than fine needle aspiration for molecular studies. In this study, we reviewed concurrently acquired fine needle aspiration and core needle biopsy samples (n=24), and compared overall cellularity, tumor fraction, and the results of next-generation sequencing. All somatic mutations detected in core needle biopsy samples were also detected in fine needle aspiration samples. The estimated tumor fraction was significantly higher in fine needle aspiration smears than core needle biopsy samples (P=0.003), whereas the overall DNA yield from smears was significantly lower than that obtained from the core needle biopsy specimens (P=0.01). The normalized average amplicon coverage for the genes analyzed was significantly higher in cytology smears than paired core needle biopsy samples, with lower numbers of failed amplicons and higher overall mutation allelic frequencies seen in the former. We further evaluated 100 malignant fine needle aspiration and core needle biopsy samples, acquired concurrently, for overall cellularity and tumor fraction. Overall cellularity and tumor fraction of fine needle aspiration samples was significantly higher than concurrently acquired core needle biopsy samples (P<0.001). In conclusion, we show that fine needle aspiration samples frequently provide better cellularity, higher tumor fraction, and superior sequencing metrics than concurrently acquired core needle biopsy samples. Cytologic specimens, therefore, should be better integrated into routine molecular diagnostics workflow to maximize limited tissues for clinically relevant genomic testing.
- Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of ...EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer.
- To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer.
- An electronic literature search in PubMed and Google databases was performed using the following key words: cytology, lung cancer, on-site evaluation, rapid on-site evaluation, and ROSE EBUS-TBNA. Only articles published in English were included in this review.
- Rapid on-site evaluation can ensure that the targeted lesion is being sampled and can enable appropriate specimen triage. If available, it should be used with EBUS-TBNA in the diagnosis of lung cancer because it can minimize repeat procedures for additional desired testing (ie, molecular studies). Some studies have shown that ROSE does not adversely affect the number of aspirations, total procedure time of EBUS-TBNA, or the rate of postprocedure complications; it is also helpful in providing a preliminary diagnosis that can reduce the number of additional invasive procedures, such as mediastinoscopy. As EBUS technology continues to evolve, our knowledge of the role of ROSE in EBUS-TBNA for the diagnosis of lung cancer will also continue to grow and evolve.
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