Purpose: Indeterminate thyroid lesions on fine needle aspiration (FNA) harbor malignancy in about 25% of cases. Hemi-or total thyroidectomy has, therefore, been routinely advocated for definitive diagnosis. In this study, we analyzed miRNA expression in indeterminate FNA samples and determined its prognostic effects on final pathologic diagnosis.Experimental Design: A predictive model was derived using 29 ex vivo indeterminate thyroid lesions on FNA to differentiate malignant from benign tumors at a tertiary referral center and validated on an independent set of 72 prospectively collected in vivo FNA samples. Expression levels of miR-222, miR-328, miR-197, miR-21, miR-181a, and miR-146b were determined using reverse transcriptase PCR. A statistical model was developed using the support vector machine (SVM) approach.Results: A SVM model with four miRNAs (miR-222, miR-328, miR-197, and miR-21) was initially estimated to have 86% predictive accuracy using cross-validation. When applied to the 72 independent in vivo validation samples, performance was actually better than predicted with a sensitivity of 100% and specificity of 86%, for a predictive accuracy of 90% in differentiating malignant from benign indeterminate lesions. When Hurthle cell lesions were excluded, overall accuracy improved to 97% with 100% sensitivity and 95% specificity.Conclusions: This study shows that that the expression of miR-222, miR-328, miR-197, and miR-21 combined in a predictive model is accurate at differentiating malignant from benign indeterminate thyroid lesions on FNA. These findings suggest that FNA miRNA analysis could be a useful adjunct in the management algorithm of patients with thyroid nodules.
Thyroid cancer is an uncommon malignancy that accounts for roughly 1% of all new cancers. Although anaplastic lesions constitute fewer than 5% of thyroid cancers, they represent over half of thyroid cancer-related deaths. The relative rarity of anaplastic thyroid cancer, its aggressive nature, and its rapidly fatal course have contributed to the difficulty in developing effective treatment for this disease. Radiation, chemotherapy, and surgery are rarely curative, but combinations of these modalities appear to offer greater benefit than any single treatment. New treatment modalities are desperately required, and promising molecular-based therapies are being investigated.
RESULTSIn all, 521 consecutive FISH tests from 300 patients were evaluated; 47% had a history of bladder cancer and 53% had suspicious symptoms. Of the 521 FISH tests, 24% were positive; concurrent cytology was available for 84% of the FISH tests, with a concordance rate of 78% (6% were positive for both and 72% were negative by both tests). For the discordant cases, FISH was positive and cytology negative in 21% of cases, and cytology was positive with a negative FISH for 1%. In all, 99 FISH tests had concurrent biopsy data. Of the 44 cases histologically positive for TCC, 32 were FISH-positive, resulting in an overall sensitivity (95% confidence interval) of 73 (60-88)%. FISH detected 95% of cases with high-grade carcinoma, while only seven of these 17 were positive by concurrent cytological assessment. FISH detected 56% and cytology detected 32% of low-grade lesions. FISH detected all nine new cases with positive histology. Overall, the specificity of FISH was 65 (53-78)%. Of 112 patients with previous TCC, 28 had a recurrence; 22 of these had positive FISH results.
CONCLUSIONFISH analysis has a high sensitivity for detecting new cases of TCC, as well as recurrences. From the present data FISH is considerably more sensitive and only slightly less specific than cytology in diagnosing TCC. Therefore, we recommend FISH as a useful initial diagnostic tool in patients suspected of both new and recurrent TCC.
KEYWORDSfluorescence in situ hybridization (FISH), UroVysion, urothelial carcinoma, detection, TCC
OBJECTIVETo determine the diagnostic sensitivity of genetic studies using fluorescence in situ hybridization (FISH) for detecting both new and recurrent cases of transitional cell carcinoma (TCC) in a routine clinical practice setting, as bladder cancer has a significant risk of recurrence and progression to invasive disease and thus sensitive surveillance testing is very important.
PATIENTS AND METHODSFISH was performed using the UroVysion TM kit (Vysis Inc., Downers Grove, IL, USA) Consecutive patients were assessed using FISH, both to evaluate those with a history of TCC or with suspicious symptoms, and the FISH results were compared with concurrent biopsy and cytological assessments.
BACKGROUND: Literature on the diagnostic yield of electromagnetic navigation bronchoscopy (ENB) with ENB-guided fine-needle aspiration (ENB-FNA) in peripheral lung lesions (PLLs) that measure 2 cm is scarce. Data on the diagnostic yield of ENB-FNA for PLLs when performed in conjunction with positron emission tomography-computed tomography (PET-CT), rapid on-site evaluation (ROSE), ENB-guided bronchial brushing (ENB-BB), and ENB-guided transbronchial biopsy (ENB-TBx) is also limited. In this study, the authors evaluated their experience with ENB-FNA performed in conjunction with all 4 modalities: PET-CT, ROSE, ENB-BB, and ENB-TBx. METHODS: ENB-FNA and other tests over a 2-yearperiod (from July 2011 to July 2013) were retrospectively reviewed. RESULTS: There were 50 PLLs from 40 patients, and the mean lesion size (available for 45 PLLs) was 2.6 cm: these included 24 PLLs that measured 2 cm and 21 PLLs that measured > 2.0 cm. The ENB-FNA diagnosis was malignant in 17 lesions, atypical in 1 lesion, benign in 31 lesions, and nondiagnostic in 1 lesion. On the basis of lesion size, the diagnostic yield of PLLs was 87% in lesions 2 cm and 100% in lesions > 2.0 cm (P 5 0.5; not significant). Follow-up available in 49 of 50 PLLs from 39 patients had an overall diagnostic yield of 94% for ENB-FNA. The diagnostic yield of PET-CT (available in 31 of 50 PLLs) and of ENB-BB and ENB-TBx (available in 40 of 50 PLLs) in conjunction with ENB-FNA was 61% and 95%, respectively. ROSE was performed in 46 of 50 PLLs: the overall sensitivity of ROSE and ENB-FNA was 85% and 89.4%, respectively, and their specificity was 96.5% and 100%, respectively. There were no procedure-related complications. CONCLUSIONS: The high overall diagnostic yield of 94% and fewer complications make ENB-FNA a useful modality for the assessment of PLLs. In this study, ROSE was useful, whereas PET-CT, ENB-BB, and ENB-TBx were not useful in the evaluation of PLLs. Cancer (Cancer Cytopathol) 2014;122:191-9.
ICAM-1 expression is upregulated in papillary thyroid carcinoma. Furthermore, ICAM-1 upregulation correlated with aggressive tumor features such as BRAF V600E mutation, ETE, and lymph node metastasis, suggesting that ICAM-1 plays a role in thyroid cancer progression.
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