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Zhonghua Bing Li Xue Za Zhi = Chinese... Jun 2024To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. There were 4 995...
To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all <0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (<0.05). Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.
Topics: Humans; Lung Neoplasms; Male; Adenocarcinoma of Lung; Female; Retrospective Studies; Anaplastic Lymphoma Kinase; Mutation; ErbB Receptors; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Receptor, ErbB-2; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-ret; Adenocarcinoma; Proto-Oncogene Proteins; Adenocarcinoma, Mucinous; Middle Aged
PubMed: 38825903
DOI: 10.3760/cma.j.cn112151-20231019-00277 -
Digestive and Liver Disease : Official... Jun 2024Factors associated with the risk of pancreatic adenocarcinoma (PDAC) may play a role in the development and progression of Intraductal Papillary Mucinous Neoplasms...
BACKGROUND
Factors associated with the risk of pancreatic adenocarcinoma (PDAC) may play a role in the development and progression of Intraductal Papillary Mucinous Neoplasms (IPMNs). However, data are limited.
AIM
To compare exposome factors in three groups of patients with "high or low-risk" IPMNs, as assessed at diagnosis and during a 24-months follow-up, and with PDAC.
METHODS
Patients were matched (same sex, age ±5) 1:1. Exposure variables were compared across groups using Kruskal-Wallis, ANOVA, or Chi-square tests with Bonferroni correction.
RESULTS
A total of 151 patients were enrolled in each of the three groups (453 overall). The proportion of current smokers was progressively higher in "low-risk", "high-risk" IPMNs and PDAC patients (8.1 %, 11.2 %, 23.3 %; p = 0.0002). The three groups did not differ in terms of ever or heavy smoking, BMI, history of diabetes, cancer, cholecystectomy or chronic pancreatitis, use of statins or aspirin, and family history of cancer. A history of peptic ulcer was more common in PDAC (7.2 %) than in either "low-risk" (2.0 %) or "high-risk" (2.6%) IPMNs (p = 0.02, not significant after Bonferroni correction).
CONCLUSION
Active smoking seems associated with the progression of IPMNs to malignancy, and cessation of active smoking might be advised in patients with IPMN.
PubMed: 38825412
DOI: 10.1016/j.dld.2024.05.017 -
Archives of Pathology & Laboratory... May 2024Intraoperative (frozen section) analysis of lung lesions (nodules, masses, ground-glass opacities) can occasionally be diagnostically challenging.
CONTEXT.—
Intraoperative (frozen section) analysis of lung lesions (nodules, masses, ground-glass opacities) can occasionally be diagnostically challenging.
OBJECTIVE.—
To describe selected pitfalls in thoracic frozen sections with a focus on the differential diagnosis between adenocarcinoma and its mimics, and to provide tips to prevent misinterpretation.
DATA SOURCES.—
Peer-reviewed literature and the author's experience.
CONCLUSIONS.—
A common challenge in thoracic frozen sections is the differential diagnosis between lung adenocarcinoma and its mimics. Diagnostic difficulties arise because mimics of adenocarcinoma often entrap reactive lung epithelium that can appear atypical on frozen section slides. Entities that can be misinterpreted as adenocarcinoma include ciliated muconodular papillary tumor/bronchiolar adenoma, hamartoma, inflammatory myofibroblastic tumor, and pulmonary Langerhans cell histiocytosis. Knowledge of the key clinical, radiologic, and histologic features of these entities can help prevent overdiagnosis of adenocarcinoma. Pathologic findings that facilitate the distinction between adenocarcinoma and its mimics at frozen section include the appearance and contour of the lesion at low magnification, growth patterns, cilia, stromal features, shape of the epithelial cells (cuboidal versus columnar), nuclear features of malignancy (crowding, hyperchromasia, irregular contours), and abruptness of the junction between the lesion and adjacent uninvolved lung. Knowledge of the clinical context, imaging findings, and the surgical consequence of the intraoperative diagnosis can also prevent diagnostic errors. Finally, since adenocarcinomas of the lung are often relatively bland and lack the stromal desmoplasia seen in adenocarcinomas of other organs, familiarity with the morphologic spectrum of lung adenocarcinomas at frozen section analysis is important.
PubMed: 38818706
DOI: 10.5858/arpa.2024-0023-RA -
Frontiers in Endocrinology 2024This study aimed to analyze the effect of preoperative fine needle aspiration cytology (FNAC) combined with BRAF mutation detection as compared to that of fine needle...
BACKGROUND
This study aimed to analyze the effect of preoperative fine needle aspiration cytology (FNAC) combined with BRAF mutation detection as compared to that of fine needle aspiration cytology alone on the diagnostic performance of papillary thyroid carcinoma (PTC) combined with Hashimoto's thyroiditis (HT).
METHOD
Patients with thyroid nodules in Hashimoto's thyroiditis, who underwent fine-needle aspiration cytology examination and BRAF mutation detection in the puncture eluate at the outpatient clinic, were selected. Finally, 122 patients received surgical treatment and were included in the study. We used postoperative pathological results as the gold standard. Accordingly, we compared the sensitivity, specificity and accuracy of preoperative FNAC alone and FNAC combined with BRAF mutation detection in for the diagnosis of PTC combined with HT.
RESULTS
For PTC patients with HT, the sensitivity of FNAC diagnosis was 93.69%, the specificity was 90.90% and the accuracy was 93.44%. However, the sensitivity, specificity and accuracy of FNAC combined with BRAF mutation detection were 97.30%, 90.90% and 96.72%, respectively. Therefore, combined detection can improve the sensitivity and accuracy of diagnosis (p<0.05).
CONCLUSION
FNAC combined with eluent BRAF mutation detection can improve the sensitivity and accuracy of diagnosis of PTC in the background of HT.
Topics: Humans; Hashimoto Disease; Proto-Oncogene Proteins B-raf; Biopsy, Fine-Needle; Female; Male; Thyroid Cancer, Papillary; Middle Aged; Adult; Mutation; Thyroid Neoplasms; Sensitivity and Specificity; Aged; DNA Mutational Analysis
PubMed: 38818506
DOI: 10.3389/fendo.2024.1366724 -
Journal For Immunotherapy of Cancer May 2024The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been...
BACKGROUND
The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets.
METHODS
This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples.
RESULTS
A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3 DCs promote CD8 T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3 DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion.
CONCLUSION
Our findings expound valuable insights into the role of the interaction between LAMP3 DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.
Topics: Humans; Dendritic Cells; Thyroid Cancer, Papillary; Lysosomal-Associated Membrane Protein 3; Thyroid Neoplasms; Male; Female; Tumor Microenvironment; Middle Aged; Tumor Escape; T-Lymphocyte Subsets; Neoplasm Proteins
PubMed: 38816233
DOI: 10.1136/jitc-2024-008983 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024We aimed to reveal the clinicopathological differences between epidermal growth factor receptor (EGFR)-mutated and wild-type (WT) lung adenocarcinoma (LUAD) focusing on...
OBJECTIVES
We aimed to reveal the clinicopathological differences between epidermal growth factor receptor (EGFR)-mutated and wild-type (WT) lung adenocarcinoma (LUAD) focusing on the predominant subtype.
METHODS
This study included 352 with EGFR mutation and 370 with WT patients in consecutive stage I LUAD classified by the predominant subtype, and their clinicopathological characteristics and prognosis were analyzed. Using the Cancer Genome Atlas Program (TCGA) cohort, we analyzed differences in gene expression between EGFR mutation and WT groups. Furthermore, we performed immunohistochemical evaluations for 46 with EGFR mutation and 47 with WT patients in consecutive stage I papillary predominant adenocarcinoma (PPA).
RESULTS
Compared to the PPA with WT [n = 115], those with EGFR mutation [n = 99] exhibited smaller invasive size (p = 0.03) and less frequent vessel invasion (p < 0.01). However, PPA with EGFR mutation showed significantly worse 5-ys recurrence-free survival (RFS) rates compared to those with WT (70.6 % versus 83.3 %, p = 0.03). Contrarily, no significant differences were observed in other predominant subtypes. In the TCGA cohort, PPA with EGFR mutation tended to show higher expression of galectin-3, which is associated with tumor metastasis and resistance to anoikis, compared to those with WT (p = 0.06). Immunohistochemical evaluation revealed that galectin-3 expression was significantly higher in PPA with EGFR mutation than in those with WT (p < 0.01).
CONCLUSIONS
The prognosis of PPA with EGFR mutation proved to be less favorable compared to that with WT, and galectin-3 is highly expressed in EGFR-mutated PPA.
Topics: Humans; ErbB Receptors; Male; Female; Mutation; Lung Neoplasms; Adenocarcinoma of Lung; Aged; Middle Aged; Prognosis; Neoplasm Staging; Biomarkers, Tumor; Galectin 3; Aged, 80 and over; Adult; Adenocarcinoma, Papillary
PubMed: 38805901
DOI: 10.1016/j.lungcan.2024.107830 -
International Journal of Nanomedicine 2024The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in... (Observational Study)
Observational Study Clinical Trial
BACKGROUND
The recurrence rate of thyroid cancer can be as high as 30%. The purpose of this study was to examine changes of urine exosomal peptide levels after thyroidectomy in patients with thyroid cancer to determine if levels can predict the risk of recurrence.
METHODS
Patients >20 years old as newly diagnosed with papillary thyroid cancer who had received a thyroidectomy were recruited. Urine samples were collected at 12 months after enrollment to the study, and 1 year later. Urine exosomes containing different peptides were identified and compared.
RESULTS
A total of 70 patients were enrolled in the study, and were classified by the interval between surgery and enrollment: 42 patients with < 5 years between surgery and enrollment, 14 patients between 5-10 years, and 14 patients longer than 10 years. No recurrence was observed in any patient during the 2 years after enrollment. No significant differences were found in the levels of serum proteins or urine exosomal peptides between groups, or between intervals. Known risk factors for high-risk thyroid cancer had only a mild correlation with serum protein levels and urine exosomal peptides.
CONCLUSION
Our study revealed the long-term basal fluctuation ranges of serum proteins and urine exosomal peptides in patients with thyroid cancer who underwent thyroidectomy. For high-risk patients after thyroidectomy, concentrations of serum proteins or urine exosomal peptides within the ranges may indicate there is a lower risk of thyroid cancer recurrence during long-term follow-up.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT03488134.
Topics: Humans; Thyroidectomy; Exosomes; Male; Thyroid Neoplasms; Female; Middle Aged; Prospective Studies; Adult; Neoplasm Recurrence, Local; Peptides; Thyroid Cancer, Papillary; Aged; Biomarkers, Tumor
PubMed: 38803995
DOI: 10.2147/IJN.S458931 -
Cureus Apr 2024Digital papillary adenocarcinoma (DPA) is a rare eccrine sweat gland tumor that often appears as a solitary, non-painful, gradually enlarging mass. Clinically, DPA...
Digital papillary adenocarcinoma (DPA) is a rare eccrine sweat gland tumor that often appears as a solitary, non-painful, gradually enlarging mass. Clinically, DPA presents considerable challenges due to its high likelihood of recurrence and its tendency to spread to the lymph nodes and lungs. This case report focuses on the surgical treatment of a unique case of DPA located on the dorsal thumb in a 46-year-old male. The patient initially underwent wide local excision with temporary wound coverage, and once final histopathological findings confirmed negative margins, a second procedure consisting of thumb interphalangeal joint fusion and first dorsal metacarpal artery flap coverage was performed. Eighteen months later, the patient continued to work in landscaping, performing the physically demanding tasks required by the job. This case demonstrates the feasibility of thumb preservation in the setting of soft tissue malignancy once negative margins are obtained.
PubMed: 38803757
DOI: 10.7759/cureus.59132 -
Frontiers in Endocrinology 2024The incidence of thyroid cancer is growing fast and surgery is the most significant treatment of it. For patients with unilateral cN0 papillary thyroid cancer whether to...
PURPOSE
The incidence of thyroid cancer is growing fast and surgery is the most significant treatment of it. For patients with unilateral cN0 papillary thyroid cancer whether to dissect contralateral central lymph node is still under debating. Here, we aim to provide a machine learning based prediction model of contralateral central lymph node metastasis using demographic and clinical data.
METHODS
2225 patients with unilateral cN0 papillary thyroid cancer from Wuhan Union Hospital were retrospectively studied. Clinical and pathological features were compared between patients with contralateral central lymph node metastasis and without. Six machine learning models were constructed based on these patients and compared using accuracy, sensitivity, specificity, area under the receiver operating characteristic and decision curve analysis. The selected models were then verified using data from Differentiated Thyroid Cancer in China study. All statistical analysis and model construction were performed by R software.
RESULTS
Male, maximum diameter larger than 1cm, multifocality, ipsilateral central lymph node metastasis and younger than 50 years were independent risk factors of contralateral central lymph node metastasis. Random forest model performed better than others, and were verified in external validation cohort. A web calculator was constructed.
CONCLUSIONS
Gender, maximum diameter, multifocality, ipsilateral central lymph node metastasis and age should be considered for contralateral central lymph node dissection. The web calculator based on random forest model may be helpful in clinical decision.
Topics: Humans; Male; Machine Learning; Female; Lymphatic Metastasis; Middle Aged; Thyroid Cancer, Papillary; Thyroid Neoplasms; Retrospective Studies; Adult; Lymph Nodes; Algorithms
PubMed: 38800481
DOI: 10.3389/fendo.2024.1385324 -
Clinical and Translational Medicine May 2024BRAF is the most common genetic mutation in differentiated thyroid cancer (DTC) occurring in 60% of patients and drives malignant tumour cell phenotypes including...
BACKGROUND
BRAF is the most common genetic mutation in differentiated thyroid cancer (DTC) occurring in 60% of patients and drives malignant tumour cell phenotypes including proliferation, metastasis and immune-escape. BRAF-mutated papillary thyroid cancer (PTC) also displays greatly reduced expression of thyroid differentiation markers, thus tendency to radioactive iodine (RAI) refractory and poor prognosis. Therefore, understanding the molecular mechanisms and main oncogenic events underlying BRAF will guide future therapy development.
METHODS
Bioinformatics and clinical specimen analyses, genetic manipulation of BRAF-induced PTC model, functional and mechanism exploration guided with transcriptomic screening, as well as systematic rescue experiments were applied to investigate miR-31 function within BRAF-induced thyroid cancer development. Besides, nanoparticles carrying miR-31 antagomirs were testified to alleviate I iodide therapy on PTC models.
RESULTS
We identify miR-31 as a significantly increased onco-miR in BRAF-associated PTC that promotes tumour progression, metastasis and RAI refractoriness via sustained Wnt/β-catenin signalling. Mechanistically, highly activated BRAF/MAPK pathway induces miR-31 expression via c-Jun-mediated transcriptional regulation across in vitro and transgenic mouse models. MiR-31 in turn facilitates β-catenin stabilisation via directly repressing tumour suppressors CEBPA and DACH1, which direct the expression of multiple essential Wnt/β-catenin pathway inhibitors. Genetic functional assays showed that thyroid-specific knockout of miR-31 inhibited BRAF-induced PTC progression, and strikingly, enhanced expression of sodium-iodide symporter and other thyroid differentiation markers, thus promoted I uptake. Nanoparticle-mediated application of anti-miR-31 antagomirs markedly elevated radio-sensitivity of BRAF-induced PTC tumours to I therapy, and efficiently suppressed tumour progression in the pre-clinical mouse model.
CONCLUSIONS
Our findings elucidate a novel BRAF/MAPK-miR-31-Wnt/β-catenin regulatory mechanism underlying clinically BRAF-associated DTC tumourigenesis and dedifferentiation, also highlight a potential adjuvant therapeutic strategy for advanced DTC.
Topics: Animals; Humans; Mice; Carcinogenesis; Cell Dedifferentiation; MicroRNAs; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 38797942
DOI: 10.1002/ctm2.1694