Follicular variants of papillary thyroid carcinoma include encapsulated (with or without capsular/vascular invasion) and infiltrative forms, which have different clinical behaviors. The encapsulated forms that lack capsular invasion have an indolent clinical behavior that is similar to benign lesions; therefore, they were recently reclassified as 'noninvasive follicular thyroid neoplasms with papillary-like nuclear features' (NIFTPs). Because NIFTPs have nuclear features of papillary carcinomas, distinguishing between NIFTPs and infiltrative follicular variant of papillary thyroid carcinoma is almost impossible with cytological examination. The aim of this study is to determine whether miRNA expression profiles may help distinguish between NIFTPs versus follicular adenomas and infiltrative follicular variant of papillary thyroid carcinomas. The expression profiling of 798 miRNAs was tested in 54 thyroid tumors, including 18 follicular adenomas, 19 NIFTPs and 17 infiltrative follicular variant of papillary thyroid carcinomas, using nCounter Nanostring. We found that miR-146-5p, miR-221-5p, miR-222-3p, miR-30e-3p, and miR-152-3p could discriminate between benign and malignant lesions with a very high level of significance (P-value<0.001). High expression levels of miR-146-5p, miR-199a-5p, miR-199b-5p, miR-1285-5p, miR-1915-3p, and miR-4516, and low miR-148b-3p expression were associated with infiltrative growth of follicular variant of papillary thyroid carcinomas. Interestingly, miR-152-3p, miR-185-5p, and miR-574-3p were significantly downregulated in NIFTPs compared with follicular adenomas, whereas miR-10a-5p and miR-320e can discriminate between NIFTPs and infiltrative forms of follicular variant of papillary thyroid carcinomas. In conclusion, a panel of these markers could have high diagnostic potential as well as could be applied to presurgical fine-needle aspiration, especially for lesions classified as indeterminate thyroid nodules.
Purpose The SARS-CoV-2 genome has been detected in a variety of human samples including blood, urine, semen, and faeces. However, evidence of virus presence in tissues other than lung are limited. Methods We investigated whether SARS-CoV-2 could be detected in 50 autoptic specimens of endocrine organs from 29 patients who died of COVID-19. Results The virus was detected in 25 specimens including ten abdominal subcutaneous adipose tissue samples (62%), six testes (67%), and nine thyroid (36%) samples. The analysis of multiple endocrine organ samples obtained from the same patients showed that, in virus-positive cases, the viral genome was consistently detected in all but two matched specimens. Conclusion Our findings show that the virus spread into endocrine organs is a common event in severe cases. Further studies should assess the rate of the phenomenon in clinically mild cases. The potential long-term effects of COVID-19 on endocrine functions should be taken into consideration.
Thyroid cancer is the most common type of endocrine-related malignancy, whose incidence rates have increased dramatically in the last few decades. Neoplasms of follicular origin generally have excellent prognosis, with the exception of less differentiated tumors. Follicular-derived thyroid cancer can manifest as a variety of morphologically distinct entities, characterized by various degrees of differentiation and invasiveness. Histological evaluation is thus crucial for the definition of patients’ prognosis. However, within each histological subtype, tumor behavior can be highly variable, and, in this respect, molecular characterization can provide insightful information to refine the risk stratification of tumors. In addition to the importance of its prognostic role, molecular testing can be used to support the differential diagnosis of thyroid nodules in the absence of marked cyto-morphological aberrations. Finally, with the advent of targeted drugs, the presence of molecular alterations will guide the therapeutic strategies for patients with advanced tumors who do not respond to standard treatment. This review aims to describe the genetic landscape of follicular-derived thyroid tumors also highlighting differences across histological subtypes.
Objective Obesity is a recognized risk factor for the progression to severe forms of COVID-19, yet the mechanisms of the association are unclear. Methods Subcutaneous abdominal adipose tissue specimens of subjects deceased from COVID-19 (n = 23) were compared to those of controls dying abruptly from causes other than infectious (accidental trauma, sudden cardiac death). Alterations of lung parenchyma consistent with moderate to severe disease were detected in all COVID-19 cases, not in controls. Investigations included: histopathologic features, detection of virus antigens and genome, characterization of infiltrating leukocytes, transcription levels of immune-related genes. Results By RT-PCR, the SARS-CoV-2 genome was detected in the adipose tissue of 13/23 (56%) cases of the COVID-19 cohort. The virus nucleocapsid antigen was detected in the cytoplasm of 1–5% adipocytes in 12/12 COVID-19 cases that were virus-positive by PCR in the adipose tissue (one case could not be assessed due insufficient tissue). The adipose tissue of COVID-19 cases showed leukocyte infiltrates and upregulation of the interferon-alpha pathway. After adjusting for age and sex, the activation score of IFN-alpha was directly related with transcription levels of the ACE2 gene, a key entry factor of SARS-CoV-2. Conclusions In lethal COVID-19 cases, the SARS-CoV-2 nucleocapsid antigen has been detected in a sizeable proportion of adipocytes, showing that the virus may directly infect the parenchymal cells of subcutaneous fat. Infection appears to activate the IFN alpha pathway and to attract infiltrating leukocytes. Due to the huge numbers of adipocytes in adults, the adipose tissue represents a significant reservoir for SARS-CoV-2 and an important source of inflammatory mediators.
The disruption of the Hippo pathway occurs in many cancer types and is associated with cancer progression. Herein, we investigated the impact of 32 Hippo genes on overall survival (OS) of cancer patients, by both analysing data from The Cancer Genome Atlas (TCGA) and reviewing the related literature. mRNA and protein expression data of all solid tumors except pure sarcomas were downloaded from TCGA database. Thirty-two Hippo genes were considered; for each gene, patients were dichotomized based on median expression value. Survival analyses were performed to identify independent predictors, taking into account the main clinical-pathological features affecting OS. Finally, independent predictors were correlated with YAP1 oncoprotein expression. At least one of the Hippo genes is an independent prognostic factor in 12 out of 13 considered tumor datasets. mRNA levels of the independent predictors coherently correlate with YAP1 in glioma, kidney renal clear cell, head and neck, and bladder cancer. Moreover, literature data revealed the association between YAP1 levels and OS in gastric, colorectal, hepatocellular, pancreatic, and lung cancer. Herein, we identified cancers in which Hippo pathway affects OS; these cancers should be candidates for YAP1 inhibitors development and testing.
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