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Biomedicine & Pharmacotherapy =... Apr 2024Oxidative stress (OS) is recognized as a contributing factor in the development and progression of thyroid cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) is... (Review)
Review
Oxidative stress (OS) is recognized as a contributing factor in the development and progression of thyroid cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor involved in against OS generated by excessive reactive oxygen species (ROS). It governs the expression of a wide array of genes implicated in detoxification and antioxidant pathways. However, studies have demonstrated that the sustained activation of Nrf2 can contribute to tumor progression and drug resistance in cancers. The expression of Nrf2 was notably elevated in papillary thyroid cancer tissues compared to normal tissues, indicating that Nrf2 may play an oncogenic role in the development of papillary thyroid cancer. Nrf2 and its downstream targets are involved in the progression of thyroid cancer by impacting the prognosis and ferroptosis. Furthermore, the inhibition of Nrf2 can increase the sensitivity of target therapy in thyroid cancer. Therefore, Nrf2 appears to be a potential therapeutic target for the treatment of thyroid cancer. This review summarized current data on Nrf2 expression in thyroid cancer, discussed the function of Nrf2 in thyroid cancer, and analyzed various strategies to inhibit Nrf2.
Topics: Humans; Thyroid Cancer, Papillary; NF-E2-Related Factor 2; Thyroid Neoplasms; Oxidative Stress; Antioxidants; Reactive Oxygen Species
PubMed: 38422655
DOI: 10.1016/j.biopha.2024.116324 -
Endocrine Pathology Sep 2023Papillary thyroid carcinoma (PTC) is considered an indolent neoplasm but it may demonstrate aggressive behavior. We aimed to identify clinical and pathological...
Papillary thyroid carcinoma (PTC) is considered an indolent neoplasm but it may demonstrate aggressive behavior. We aimed to identify clinical and pathological characteristics and molecular signatures associated with aggressive forms of PTCs. We selected 43 aggressive PTC cases based on the presence of metastases at the time of diagnosis, the development of distant metastasis during follow-up, and/or biochemical recurrence, and 43 PTC patients that were disease-free upon follow-up, matching them according to age, sex, pT, and pN parameters. Twenty-four pairs (a total of 48 cases) and 6 normal thyroid tissues were studied using targeted mRNA screening of cancer-associated genes employing NanoString nCounter technology. In general, aggressive PTCs showed distinctive clinical and morphological features. Among adverse prognostic parameters, the presence of necrosis and an increased mitotic index were associated with shorter disease-free and overall survivals. Other parameters associated with shorter disease-free or overall survivals include a lack of tumor capsule, the presence of vascular invasion, tumor-infiltrating lymphocytes, fibrosclerotic changes, age > 55 years, and a high pTN stage. Various pathways were differentially regulated in non-aggressive as compared to aggressive PTC, including the DNA damage repair, the MAPK, and the RAS pathways. In particular, the hedgehog pathway was differentially de-regulated in aggressive PTC as compared to non-aggressive PTC cases, being WNT10A and GLI3 genes significantly up- and down-regulated in aggressive PTC and GSK3B up-regulated in non-aggressive PTC cases. In conclusion, our study revealed specific molecular signatures and morphological features in aggressive PTC that may be useful to predict more aggressive behavior in a subset of PTC patients. These findings may be useful when developing novel, tailored treatment options for these patients.
Topics: Humans; Middle Aged; Thyroid Cancer, Papillary; Transcriptome; Thyroid Neoplasms; Carcinoma, Papillary; Hedgehog Proteins; Prognosis
PubMed: 37208504
DOI: 10.1007/s12022-023-09769-x -
Deutsches Arzteblatt International Oct 2023Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform... (Review)
Review
BACKGROUND
Ampullary or papillary carcinoma is a malignant tumor arising from the mucosa in the region of the major duodenal papilla, also known as the ampulla of Vater. Uniform treatment recommendations are lacking both for the adjuvant situation and for palliative care.
METHODS
A selective literature search was carried out in PubMed in order to identify the most informative publications concerning the epidemiology, clinico-pathological background, and surgical and medical treatment of this condition.
RESULTS
Ampullary carcinoma has an incidence of 0.5 to 0.9 per 100 000 persons and a poor prognosis, with a 5-year survival rate of 41% to 45% for locally confined and 4% to 7% for metastatic disease. Most such tumors are of an intestinal or a pan - creaticobiliary immunohistochemical subtype; the latter has a worse prognosis (median survival, 72-80 vs. 33-41 months). Targeted treatment is not yet available for either subtype, nor is there enough scientific evidence available for the formulation of specific therapeutic recommendations in either the adjuvant or the palliative situation. The treatment of choice for ampullary carcinoma is radical oncological resection of the head of the pancreas with systematic lymphadenectomy. Five-year overall survival is between 10% and 75% depending on the stage. No definitive recommendation for adjuvant therapy can be given. Palliative therapy can be oriented to the published treatment strategies for cancer of the colon, pancreas, and bile duct.
CONCLUSION
The current state of the evidence on the treatment of ampullary carcinoma is poor. Therapeutic decisions should be discussed in an interdisciplinary tumor board and should, in our opinion, take the histological subtype into account.
Topics: Humans; Ampulla of Vater; Adenocarcinoma; Prognosis; Pancreatic Neoplasms; Combined Modality Therapy
PubMed: 37656482
DOI: 10.3238/arztebl.m2023.0195 -
Journal of Cancer Research and... 2023Solitary thyroid nodule should raise a suspicion of malignancy, which is very common in middle-aged females. Papillary carcinoma thyroid is the most common thyroid...
Solitary thyroid nodule should raise a suspicion of malignancy, which is very common in middle-aged females. Papillary carcinoma thyroid is the most common thyroid malignancy. Warthin-like papillary carcinoma is one of its rare variants. It has a frequent association with Hashimoto's thyroiditis. Here, we report a case of 43-year-old female who presented with swelling in the anterior aspect of neck for 1 month. Fine-needle aspiration cytology features were suggestive of papillary carcinoma thyroid and biopsy confirmed the diagnosis of Warthin-like papillary carcinoma thyroid. This variant is of great clinical and prognostic significance as it carries an excellent prognosis.
Topics: Middle Aged; Female; Humans; Adult; Carcinoma, Papillary; Thyroid Cancer, Papillary; Thyroid Neoplasms; Biopsy, Fine-Needle
PubMed: 37787334
DOI: 10.4103/jcrt.jcrt_1028_21 -
Medicine Dec 2023To retrospectively analyze the diagnosis and treatment of secondary hyperparathyroidism (SHPT) combined with thyroid disease, and to investigate the correlation between...
To retrospectively analyze the diagnosis and treatment of secondary hyperparathyroidism (SHPT) combined with thyroid disease, and to investigate the correlation between SHPT and papillary thyroid carcinoma (PTC), SHPT and thyroid disease, and the importance of preoperative localization diagnosis in patients with SHPT. Clinical data of 101 patients who underwent surgical treatment for SHPT at the Third Hospital of Hebei Medical University were collected from August 2014 to May 2023, and patients were divided into SHPT without PTC group (n = 94) and SHPT with PTC group (n = 7) according to their postoperative pathology. Patients were divided into SHPT without thyroid disease group (n = 32) and SHPT with thyroid disease group (n = 69) according to their preoperative ultrasound diagnosis and postoperative pathology. The differences between the 2 groups were compared to explore the association between SHPT and PTC and between SHPT and thyroid disease. Of the 101 patients with SHPT, 65 were male and 36 were female with a mean age of (44.26 ± 11.16) years. There were 69 patients (68.32%) with concomitant thyroid disease and 32 patients (31.68%) without concomitant thyroid disease, including 7 patients (6.93%) with PTC. The results of univariate analysis showed that the differences in age and preoperative PTH levels between the SHPT without PTC group and the SHPT with PTC group were statistically significant (P < 0. 05),There were no significant differences in age, gender, preoperative PTH, preoperative alkaline phosphatase, preoperative serum calcium, preoperative serum phosphorus, preoperative serum creatinine, duration of dialysis disease, and whether they were accompanied by hypertension or not between the SHPT without thyroid disease group and the SHPT with thyroid disease group (P > 0. 05), logistic regression analysis showed that there was a correlation between the age of patients with SHPT and the level of preoperative PTH with PTC. In patients with SHPT, concomitant thyroid disease is more common, so patients with SHPT should be screened for thyroid disease at the same time as routine preoperative ultrasonography combined with nuclear scan for localized diagnosis, and surgical resection is preferred if concomitant PTC is present.
Topics: Humans; Male; Female; Adult; Middle Aged; Retrospective Studies; Renal Dialysis; Hyperparathyroidism, Secondary; Thyroid Cancer, Papillary; Thyroid Neoplasms; Parathyroid Hormone
PubMed: 38115353
DOI: 10.1097/MD.0000000000036514 -
Scientific Reports Oct 2023Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy with a rapidly increasing incidence. The pathogenesis of PTC is unclear, but metabolic and...
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy with a rapidly increasing incidence. The pathogenesis of PTC is unclear, but metabolic and lipidomic reprogramming may play a role in tumor growth. We applied ultra-performance liquid chromatography-tandem mass spectrometry to perform widely targeted metabolomics and lipidomics on plasma samples from 94 patients with PTC and 100 healthy controls. We identified 113 differential metabolites and 236 differential lipids, mainly involved in branched-chain amino acid metabolism, glutamate and glutamine metabolism, tricarboxylic acid cycle, and lipid metabolism. We also screened three potential metabolite biomarkers: sebacic acid, L-glutamine, and indole-3-carboxaldehyde. These biomarkers showed excellent diagnostic performance for PTC in both discovery and validation cohorts, with areas under the receiver operating characteristic curves of 0.994 and 0.925, respectively. Our findings reveal distinct metabolic and lipidomic features of PTC and provide novel targets for diagnosis and treatment.
Topics: Humans; Thyroid Cancer, Papillary; Lipidomics; Thyroid Neoplasms; Carcinoma, Papillary; Metabolomics; Metabolome; Biomarkers; Biomarkers, Tumor
PubMed: 37848492
DOI: 10.1038/s41598-023-41176-4 -
The American Journal of Surgical... Oct 2023Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in...
Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in digital papillary adenocarcinoma (DPA). The main objectives of the present study were (i) to provide an overview of the prevalence of previously identified oncogenic drivers in acral sweat gland tumors and (ii) to genetically characterize tumors in which no recurrent genetic alteration has been identified yet. Cases of acral sweat gland tumors were identified from the database of the French network CARADERM. After histologic review, the presence of previously identified genetic alterations was investigated in the entire cohort (n=79) using a combination of immunohistochemistry and targeted DNA and RNA sequencing. Tumor entities with no recurrent genetic alterations were submitted to whole-transcriptome sequencing. CRTC1::MAML2 fusion was identified in cases of hidradenoma and hidradenocarcinoma (n=9/12 and n=9/12). A p.V600E mutation of BRAF was observed in all cases of tubular adenoma (n=4). YAP1:MAML2 and YAP1::NUTM1 fusions were observed in poroid tumors (n=15/25). ETV6::NTRK3 and TRPS1::PLAG1 fusion transcripts were identified in secretory carcinoma (n=1/1) and cutaneous mixed tumors (n=3/4), respectively. The HPV42 genome was detected in most cases of DPA (n=10/11) and in 1 adnexal adenocarcinoma not otherwise specified. Finally, whole-transcriptome analysis revealed BRD3::NUTM1 or NSD3::NUTM1 fusions in 2 cases of NUT adnexal carcinoma and NCOA4::RET and CCDC6::RET fusion transcripts in 2 cystadenoma/hidrocystoma-like tumors. Our study confirms distinctive cytogenetic abnormalities in a wide number of acral adnexal neoplasms and supports the use of molecular analysis as a valuable aid in the diagnosis of these rare and often difficult to diagnose group of neoplasms.
Topics: Humans; Sweat Gland Neoplasms; Skin Neoplasms; Carcinoma; Acrospiroma; Transcription Factors; Adenocarcinoma, Papillary; Repressor Proteins
PubMed: 37505808
DOI: 10.1097/PAS.0000000000002098 -
Revista Espanola de Enfermedades... Jan 2024We present the case of an 82-year-old woman with a history of well-differentiated adenocarcinoma of the cecum, stage pT3N1M0, treated ten years before with right...
We present the case of an 82-year-old woman with a history of well-differentiated adenocarcinoma of the cecum, stage pT3N1M0, treated ten years before with right hemicolectomy and adjuvant chemotherapy (Capecitabine and Bevacizumab). She developed painless obstructive jaundice of sudden onset. Computed tomography (CT) showed an ampullary nodule with secondary dilatation of the biliary and the pancreatic ducts. Subsequent duodenoscopy and endoscopic ultrasound identified the presence of multiple 3-10 mm tumor-like nodules from the first to the second duodenal knee, the largest one infiltrating the papillary area and preventing its cannulation. Biopsy revealed a moderately differentiated adenocarcinoma with cribriform, nidiform and acinar architectural patterns and positive immunohistochemistry for CK20 and CDX2, compatible with colon origin. The patient was treated with five cycles of chemotherapy (FOLFOX) with the disappearance of the duodenal nodules, although during follow-up she developed disease progression with a left adnexal metastasis with identical histological and immunohistochemical pattern.
PubMed: 38258804
DOI: 10.17235/reed.2024.10089/2023 -
Indian Journal of Cancer Oct 2023Concurrence of medullary and papillary thyroid carcinoma (MTC and PTC) represents less than 1% of all thyroid malignancies. We aimed to reveal the demographic and...
PURPOSE
Concurrence of medullary and papillary thyroid carcinoma (MTC and PTC) represents less than 1% of all thyroid malignancies. We aimed to reveal the demographic and clinical characteristics of this rare pathology and to evaluate the effect of the same or contralateral lobular localization of these two malignancies in clinical and laboratory features. Evaluation of progression-free survival (PFS) in current pathology is one of the important features of our study.
METHODS
All patients diagnosed with simultaneous MTC and PTC after thyroidectomy were evaluated retrospectively. Data on the following variables were recorded: age, gender, tumor localization (ipsilateral lobe located MTC and PTC-Group I, contralateral lobe located MTC and PTC-Group II), tumor size, cervical lymph node metastasis, distant metastasis, tumor stage, postoperative basal calcitonin, carcinoembryonic antigen, thyroglobulin (Tg), and anti-Tg values. In all our cases, since MTC progressed before PTC, progression was accepted as serum calcitonin values exceeded 150 pg/mL.
RESULTS
Groups were formed as follows: Group I, four cases where MTC and PTC were localized in different foci in the same lobe; Group II, nine cases where they were localized in different lobes. There was only one case in which two tumors were located in the same focus. The case with dual differentiation was included in Group I (35. 7%). When the PFS of the two groups were compared, no statistically significant difference was found ( P = 0.87).
CONCLUSIONS
As a result of this analysis, the location of the simultaneously detected PTC in the same or different lobes with the MTC does not make a significant difference in clinical and laboratory features.
Topics: Humans; Thyroid Cancer, Papillary; Calcitonin; Survival Rate; Retrospective Studies; Carcinoma, Papillary; Thyroid Neoplasms; Carcinoma, Neuroendocrine
PubMed: 38090963
DOI: 10.4103/ijc.IJC_9_21