The association between integrin ß4 overexpression and lymphovascular invasion in papillary thyroid cancer.

INTRODUCTION: Lymphovascular invasion is an independent prognostic marker in papillary thyroid carcinomas. In addition, integrin ß4 is associated with advanced progression and metastasis in many malignancies. We aimed to investigate the relationship between integrin ß4 and lymphovascular invasion in papillary thyroid carcinoma. MATERIAL AND METHODS: 73 patients with papillary thyroid cancer (48 patients with lymphovascular invasion and 25 patients without) were included in our study. The immunohistochemical staining score for integrin b4 was evaluated according to the percentage and intensity of staining. The staining intensity was scored as 0 (no staining), 1 (weak staining - light yellow), 2 (medium staining - yellow-brown), and 3 (strong staining - brown). The staining was scored by multiplying the percentage and intensity of staining. RESULTS: The mean percentage of integrin b4 staining was 63.54 ± 22.26% in the group with lymphovascular invasion and 10.2 ± 22.48% in the group without lymphovascular invasion (p < 0.001). When evaluated in terms of staining score, it was found to be 107.08 ± 45.29 in the group with lymphovascular invasion and 16.2 ± 40.03 in the group without lymphovascular invasion (p < 0.001). There was a linear relationship between the percentage of integrin ß4 and the staining scores (r² = 0.881; p < 0.001). In the by receiver-operating characteristic (ROC) curve analysis for the cut-off value of the percentage of integrin b4 staining, the area under the curve was found to be 0.916. The cut-off value for the percentage of integrin b4 was found to be 35 (sensitivity 91.7% and specificity 88%) (odds 80.66%). CONCLUSIONS: A significant relationship was found between integrin b4 expression and lymphovascular invasion in papillary thyroid carcinomas. Integrin b4 expression level can be used as a marker to predict the presence of lymphovascular invasion in papillary thyroid carcinomas, especially in large tumours where it may not be possible to sample the entire tumour.

Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

The Impact of Total Tumor Diameter on Lymph Node Metastasis and Tumor Recurrence in Papillary Thyroid Carcinomas.

(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs ≤ 10 mm, TTDs > 10 mm, TTDs ≤ 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease.

Tumor Microenvironment Features as Predictive Biomarkers in Metastatic Differentiated Thyroid Cancer and Their Relationship With 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Metabolic Parameters.

OBJECTIVE: The role of the tumor microenvironment in tumor progression and treatment response is being investigated for different types of cancer. This study aimed to determine the relationships between tumor microenvironment, histopathology, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based metabolic parameters, treatment response, and overall survival (OS) in metastatic differentiated thyroid cancer (DTC).  Methods: Metastatic DTC patients who underwent 18F-FDG PET/CT between 2015-2019 were evaluated. Clinicopathological, histopathological features and PET/CT parameters of patients were recorded. Microenvironmental characteristics of the primary tumor, such as mitosis, intratumoral and peritumoral lymphocytosis, intratumoral and peritumoral fibrosis, were evaluated from the tissue samples. The relationships between these factors were statistically analyzed. RESULTS:  Sixty-five patients (38 females, 27 males, age: 49±15 years) were included. Mitosis, intra/peritumoral lymphocytosis, and intra/peritumoral fibrosis were frequent; however, none of them had a statistically significant association with PET-positive metastases, treatment response, or OS. Univariate analysis showed that gender, size, thyroglobulin values, residual thyroid tissue, PET-positive metastases, and maximum standardized uptake value (SUVmax) were significant predictors of OS. At multivariate analysis, PET-positive metastases (HR=-2.65, 95%CI 0.007-0.707, p=0.024) and SUVmax (HR=-2.74, 95%CI 0.006-0.687, p=0.023) were the only independent predictors for OS.  Conclusion: Our study revealed that microenvironmental characteristics of the primary tumor did not show prognostic significance in metastatic DTC. PET-positive metastases and SUVmax levels were the only significant factors that predicted overall survival in DTC. Supporting the results of our study with further studies with a larger sample size may be necessary to determine the relationship between the tumor microenvironment and prognosis in DTC.

Association of MG53 with presence of type 2 diabetes mellitus, glycemic control, and diabetic complications.

OBJECTIVES: Mitsugumin 53 (MG53) is a myokine that acts as a membrane repair protein in tissues. Data on the effect of MG53 on insulin signaling and type 2 diabetes mellitus (T2 DM) are still unknown; most are from preclinical studies. Nevertheless, some researchers have argued that it may be a new pathogenic factor, and therapies targeting MG53 may be a new avenue for T2 DM. Our study aims to evaluate the relationship of circulating MG53 levels with the presence of diabetes, diabetic complications, and glycemic control. METHODS: We conducted a case-control study with 107 patients with T2 DM and 105 subjects without insulin resistance-related disease. Concurrent blood samples were used for serum MG53 levels and other biochemical laboratory data. MG53 concentration was measured using Human-MG53, an enzyme-linked immunosorbent assay kit (Cat# CSB-EL024511HU). RESULTS: We found no difference in MG53 levels between the diabetic and control groups (p = 0.914). Furthermore, when the subjects were divided into tertiles according to their MG53 levels, we did not find any difference between the groups in terms of the presence of diabetes (p = 0.981). Additionally, no correlation was observed between weight, BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, albumin excretion in the urine, e-GFR levels, and MG53. Finally, MG53 levels were similar between the groups with and without microvascular and macrovascular complications of diabetes. CONCLUSION: Our research finding provides insightful clinical evidence of lack of association between the levels of MG53 and T2 DM or glycemic control, at least in the studied population of Turkeys ethnicity. However, further clinical studies are warranted to establish solid evidence of the link between MG53, insulin resistance and glycemic control in a wider population elsewhere in the world.

Assessment of three different radioiodine doses for ablation therapy of thyroid remnants: Efficiency, complications and patient comfort.

I-131 radioiodine (RAI) ablation removes postoperative residual tissue and facilitates follow-up in low- and intermediate-risk differentiated thyroid cancer (DTC). Although low doses have been reported to be as effective as higher doses for ablation, the doses administered still vary depending on the patient and the practitioner. We aimed to evaluate the ablation efficiency, complications, and length of stay (LOS) of patients with DTC treated with 3 different doses for ablation. Patients with DTC who received RAI therapy were retrospectively reviewed. One hundred thirty patients with low-intermediate-risk, according to American Thyroid Association classification, without known lymph nodes or distant metastases were included. Patients were divided into 3 groups as 30 to 50 mCi, 75 mCi, and 100 mCi. Residue thyroid and salivary glands were evaluated from 9 to 12 months post-RAI I-131 scans. No significant difference was found between groups regarding ablation success (P = .795). In multivariable analyses, pretreatment thyroglobulin (hazard ratio = 0.8, 95% confidence interval 0.601-0.952, P = .017) and anti- thyroglobulin antibody (hazard ratio = 1.0, 95% confidence interval 0.967-0.998, P = .024) were 2 independent predictors of ablation success. The mean LOS was 2.1 ±â€…0.3, 2.6 ±â€…0.6, and 2.9 ±â€…0.4 days, respectively, (P = .001). LOS rates of ≥ 3 days were 13.2%, 54.3%, and 84.8%, respectively. Mild decreases in hemoglobin, white blood cell (WBC), and platelet counts were observed in all groups after 6 weeks without any clinically significant findings. A lower rate of change in WBC counts was observed in the 30 to 50 mCi group compared to others. There was no dose-dependent difference regarding the early complaints questioned. Ablation with 30 to 50 mCi provides benefits such as shorter LOS, better patient comfort, less salivary gland dysfunction, and less WBC suppression, thus reducing costs without decreasing efficacy.