Role of ST6GAL1 in Thyroid Cancers: Insights from Tissue Analysis and Genomic Datasets.

Thyroid cancer is the predominant endocrine-related malignancy. ST6 ß-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.

Expression Pattern of Sonic Hedgehog, Patched and Smoothened in Clear Cell Renal Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the deadliest neoplasm of the urinary tract, and we are still far from completely understanding ccRCC development and treatment. The renal tissue paraffin blocks (20) of patients with ccRCC were collected at the University Hospital in Split from 2019 to 2020, and tissue sections were stained with patched (PTCH), anti-smoothened (SMO) and anti-Sonic Hedgehog (SHH) antibodies. SHH was highly expressed (31.9%) in grade 1 tumour, it being higher than all other grades and the control (p < 0.001-p < 0.0001). The trend of a linear decrease in the expression of SHH was observed with the progression of the tumour grade (p < 0.0001). PTCH expression was significantly lower in grades 1 and 2 in comparison to the control (p < 0.01) and grade 4 (p < 0.0001). A significant increase in the expression of SMO was found in grade 4 compared to all other grades (p < 0.0001) and the control (p < 0.001). The strong expression of SHH was observed in carcinoma cells of the G1 stage with a diffuse staining pattern (>50% of neoplastic cells). Stroma and/or inflammatory infiltrate display no staining and no expression of SHH in G1 and G2, while mild focal staining (10-50% of neoplastic cells) was observed in G3 and G4. Patients with high PTCH and low SMO expression had significant time survival differences (p = 0.0005 and p = 0.029, respectively). Therefore, high levels of PTCH and low levels of SMO expression are important markers of better survival rates in ccRCC patients.

Cardiac myxoma: benign, but deadly disease.

.

AATF and SMARCA2 are associated with thyroid volume in Hashimoto's thyroiditis patients.

Thyroid volume of Hashimoto's thyroiditis (HT) patients varies in size over the course of disease and it may reflect changes in biological function of thyroid gland. Patients with subclinical hypothyroidism predominantly have increased thyroid volume whereas patients with more pronounced hypothyroidism have smaller thyroid volumes. Suggested mechanism for thyroid atrophy is thyrocyte death due to apoptosis. We performed the first genome-wide association study (GWAS) of thyroid volume in two groups of HT patients, depending on levothyroxine (LT4) therapy, and then meta-analysed across. Study included 345 HT patients in total and 6 007 322 common autosomal genetic variants. Underlying hypothesis was that genetic components that are involved in regulation of thyroid volume display their effect in specific pathophysiologic conditions of thyroid gland of HT patients. We additionally performed immunohistochemical analysis using thyroid tissues and analysed differences in expression levels of identified proteins and apoptotic marker between HT patients and controls. We found genome-wide significant association of two loci, both involved in apoptosis, with thyroid volume of HT patients: rs7212416 inside apoptosis-antagonizing transcription factor AATF (P = 8.95 × 10-9) and rs10738556 near chromatin-remodeling SMARCA2 (P = 2.83 × 10-8). In immunohistochemical analysis we observed that HT patients with homozygous AATF risk genotypes have decreased AATF expression (0.46-fold, P < 0.0001) and increased apoptosis (3.99-fold, P = 0.0001) in comparison to controls. HT patients with heterozygous SMARCA2 genotypes have decreased SMARCA2 expression, albeit without reaching statistical significance (1.07-fold, P = 0.5876), and significantly increased apoptosis (4.11-fold, P < 0.0001). By two lines of evidence we show that two highly plausible genetic loci, AATF and SMARCA2, may be involved in determining the thyroid volume of HT patients. The results of our study significantly add to the current knowledge of disturbed biological mechanisms in thyroid gland of HT patients.

Effect of Methimazole Therapy on Thyroid Pathohistology That May Mimic Thyroid Malignancy.

Diffuse toxic goiter, as the most common cause of hyperthyroidism, is usually initially treated with thyrostatic drugs such as methimazole, followed by radioiodine therapy or surgery which may be indicated as definitive treatment. Radioactive iodine therapy has a known association with various histopathologic features including cytologic atypia, but herein we present a rare example of morphological thyrocyte changes induced by long-term pharmacological treatment with methimazole that mimicked thyroid malignancy in a pathohistological sample.

Association between EGFR expression and clinical outcome of laryngeal HPV squamous cell carcinoma.

Background: Expression of the epidermal growth factor receptor (EGFR) and human papillomavirus (HPV) DNA can serve as independent prognostic factors in squamous cell carcinoma (SCC) of the larynx. EGFR correlation with the course of disease and its effect on survival makes EGFR expression a negative prognostic factor, whereas HPV DNA is a positive prognostic factor. Aim: To assess the association of EGFR expression with clinical outcome of laryngeal HPV SCC. Materials and methods: This retrospective study included 196 SCC patients operated on at the Department of ENT, Head and Neck Surgery, Split University Hospital Center in Split, Croatia, between 1 January 2000 and 31 December 2009. Results: The association of HPV infection and EGFR expression was found to be statistically significant, and so was the difference in survival between patient groups with different HPV to EGFR expression ratio. Conclusions: The group of laryngeal HPV SCC patients with increased EGFR expression had shorter survival, confirming EGFR as a major component in predicting patient prognosis and survival. Significance: This article confirms the importance of EGFR expression as a biomarker in laryngeal SCC.

Diagnosis of Helicobacter pylori infection : A short review.

Helicobacter pylori infections represent an important factor in the pathogenesis of chronic gastritis, peptic ulcer, MALT lymphoma and gastric adenocarcinoma. The recently published Maastricht V/Florence consensus report indicated that the urea breath test using 13 C urea still remains the best non-invasive test to diagnose H. pylori infections with high sensitivity and specificity. Among the stool antigen tests, the ELISA monoclonal antibody test is a rational option. Effective therapy should be based only on susceptibility testing in regions with documented high clarithromycin resistance (>15%). Advanced high-resolution endoscopic technologies enable increased diagnostic accuracy for detection of H. pylori infections.

RET EXPRESSION AND ITS CORRELATION WITH CLINICOPATHOLOGIC DATA IN PAPILLARY THYROID CARCINOMA.

- The purpose of this study was to analyze the possible prognostic value of RET mutation in papillary thyroid carcinoma and its incidence in the past few decades in our population, due to the increasing incidence of papillary thyroid carcinoma. The present study included 180 patients operated for papillary thyroid carcinoma. The clinical and histopathologic characteristics were analyzed. Paraffin sections of the selected histologic slides were cut again and immunohistochemically stained by the Clone 3F8 P (HIER) from Novocastra (Vision Bio Systems Europe, Newcastle upon Tyne, UK) monoclonal antibody to RET oncoprotein. Univariate analysis indicated sex (p=0.01), histologic subtype (p=0.075) and capsular invasion (p=0.010) to be statistically significant predictors of lymph node metastases, whereas age (p=0.796), tumor size (p=0.556) and intraglandular dissemination (p=0.131) showed no such correlation. The presence of RET mutation (p=0.704) was not a statistically significant predictor of the tumor metastasizing potential. RET mutation (p=0.500) showed no statistically significant correlation with papillary thyroid carcinoma classifed into prognostic groups according to clinicopathologic features either. RET mutation was detected in 30% of 180 papillary thyroid carcinomas. This is the first large study demonstrating that RET mutation incidence in papillary thyroid carcinoma in Croatian population is consistent with the classic distribution of sporadic cases, despite the increased prevalence of papillary thyroid carcinoma in the past few decades.

Cyclin D1, Ret and P27 Expression in Papillary Thyroid Microcarcinoma

Th e aim of the study was to determine the influence of RET, p27 and cyclin D1 on regional lymph node metastases in papillary microcarcinoma. The analysis included 70 patients with papillary thyroid microcarcinoma that underwent surgery at Split University Hospital Center between 1999 and 2001. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue by the RET, p27 and cyclin D1 antibodies. Quantification was based on the intensity and distribution of nuclear staining, dividing tumors into those that showed expression (expressors) and those that showed no expression (non-expressors). Univariate analysis using χ²-test and Fisher exact test was performed with the level of statistical significance set at p<0.05. There was no statistically significant difference in the incidence of metastases according to the expression or non-expression of RET mutation (χ²-test: p=0.459; Fisher exact test: p=0.672). Among 25 cases with cyclin D1 expression, 6 had metastases, whereas only 2 of 45 cases with no cyclin D expression had metastases (χ²-test: p=0.014; Fisher exact test: p=0.021), indicating that the expression of cyclin D1 is not crucial for the development of metastases in lymph nodes. In contrast, analysis of p27 expression showed it to be significantly associated with lymph node metastasis because 3 of 45 patients with p27 expression had metastases, indicating a statistically significant correlation between p27 expression and lymph node metastases (χ²-test: p=0.093; Fisher exact test: p=0.124). This study confirmed the importance of the evaluation of RET, p27 and cyclin D1 expression and demonstrated the validity of their application in the assessment of microcarcinoma behavior.

Epidermal growth factor receptor (EGFR) expression in patients with laryngeal squamous cell carcinoma.

To assess the epidermal growth factor receptor (EGFR) correlation with histopathologic and clinical characteristics of laryngeal squamous cell carcinoma (SCC) and the impact of EGFR overexpression on patient survival. This retrospective study included 185 SCC patients treated at Clinical Department of ENT, Head and Neck Surgery, Split University Hospital Center between January 1, 2000 and December 31, 2009. A statistically significant correlation (p < 0.001) was recorded between the level of EGFR expression and SCC histopathologic grade, stage, metastasizing potential, relapsing potential, and patient survival. Kaplan-Meier survival curve yielded a statistically significant difference (χ(2) = 75.05; p < 0.001) among the four patient groups with different levels of EGFR expression. The higher the level of EGFR expression, the poorer is the patient prognosis and survival. In our study, expression of EGFR as a biomarker showed a potential predictive value in laryngeal SCC.

Comparison of thermal damage of the internal thoracic artery using ultra high radiofrequency and monopolar diathermy.

BACKGROUND: The internal thoracic artery (ITA) has been accepted worldwide as a first choice conduit for myocardial revascularisation. It still remains questionable what is the best method for ITA harvesting in a skeletonized fashion according to structural integrity of artery, as a risk factor of early and late graft failure. The purpose of this study was to determine the impact of the ultra-high radiofrequency energy used for ITA harvesting on arterial structural integrity, in particular on the endothelial layer. METHODS: Seventy-four ITA specimens were divided into two groups depending on device used for harvesting (radiofrequency-knife (RF) or electrocauter (EC)). Thermal damage on arterial structural integrity was measured using light microscope, morphometric imaging analysis and immunohistochemical methods. RESULTS: Thermal damage of endothelium was 2.8 times higher in EC than in RF group (p = 0.041) and 5 times higher in patients older than 66 years of age (p = 0.002). Extent of endothelial damage (graded from 0 to 3) was significantly higher in EC group (p = 0.03). Also, in EC group, in patients older than 66 years of age higher proportion of extent of endothelial damage was found (p = 0.027). CONCLUSIONS: The endothelial damage was more often in EC than in RF group as in the patients older than 66 years of age. Demonstrated results suggest that the radiosurgery in comparison to conventional electrocautery is safe and effective method, and significantly reduces thermal damage to endothelial layer of artery.

Expression of matrix metalloproteinase-9 in patients with squamous cell carcinoma of the larynx.

Aim of this study was to investigate the correlation of matrix metalloproteinase-9 (MMP-9) expression with histopathologic and clinical characteristics of laryngeal squamous cell carcinoma, and to assess the role of MMP-9 expression in patient survival. Study included 196 patients with squamous cell carcinoma of the larynx treated at ENT Department, Split University Hospital Centre, from January 1, 2000 till December 31, 2009. The level of MMP-9 expression showed a statistically significant correlation (p < 0.001) with the disease histopathologic grade, stage, metastatic potential, recurrence potential, and survival. Kaplan-Meier curve yielded a statistically significant survival difference (p < 0.001) among the three patient groups with different levels of MMP-9 expression. The survival curve clearly showed the MMP-9 expression as a predictor of survival to be significantly (p < 0.001) associated with survival. In this study, MMP-9 expression as a biological marker showed a potential predictive value in laryngeal squamous cell carcinoma.

Primary laryngeal NK/T-cell non-Hodgkin lymphoma: a case report.

The estimated prevalence of extranodal non-Hodgkin lymphoma ranges from 10 to 35% of all cases; a finding in the larynx is extremely rare. We describe the case of a 77-year-old man who presented for evaluation of a 1-month history of minor swallowing difficulty, cough, and a foreign-body sensation in the throat. Fiberoptic endoscopy detected a tumor mass on the left aryepiglottic fold. Vocal fold mobility was normal. A biopsy specimen was obtained, and microscopic analysis revealed that the stratified squamous epithelium was partially eroded by abundant infiltrate that had occupied the entire submucosa. The submucosal infiltration consisted of lymphatic cells, including small, medium-sized, and large cells with an anaplastic appearance. On immunohistochemical analysis, the lymphoma cell population stained positive for CD3 and CD2, focally positive for CD56, and negative for CD4, CD5, and CD7. In addition, tumor cells expressed TIA-1, perforin, and granzyme B. A complete radiologic, pulmonologic, and hematologic workup found no other tumor. The patient underwent two cycles of chemotherapy followed by radiotherapy, and he experienced complete tumor regression. At the 1-year follow-up, findings on fiberoptic endoscopy of the larynx were normal, and positron-emission tomography found no evidence of a recurrence. The prognosis for this type of tumor is good when the diagnosis is made in the early phase of the disease. Long-term follow-up is advisable for the timely detection of possible local or distant recurrences, which are common.

Echocardiographic appearance of a hydatid cyst of the papillary muscle and chordae tendineae.

A 24-year-old woman with a history of hydatid disease of the lung and brain, which was treated surgically and medically with albendazole, was admitted because of syncope. Echocardiography demonstrated a mass in the anterolateral papillary muscle and chordae tendineae. Despite negative serologic tests for Echinococcus granulosus, cytology and histology of the surgically removed mass confirmed hydatid disease. The patient was discharged and treated further with albendazole and praziquantel.

Preoperative Tc-99m-pertechnetate scan visualization of gross neck metastases from microcarcinoma papillare and another papillary carcinoma of tall cell variant scintigraphically presented like small warm nodule in Graves disease patient.

PURPOSE: Preoperative scintigraphic visualization of metastases from well-differentiated thyroid microcarcinoma in patients with Graves disease is extremely rare, as is the scintigraphic visualization of poorly differentiated thyroid carcinoma as a warm nodule. We present a patient with Graves disease and both of these rare entities. CASE REPORT: A 47-year-old woman complained of a growing left-side neck mass and symptoms of thyrotoxicosis. On clinical examination, the thyroid was palpable without discernible nodularity, while the left side of the neck was occupied by 3 gross, painless nodules. She also had signs of thyrotoxicosis and biochemical parameters of Graves hyperthyroidism. Ultrasound examination showed moderately hypoechogenic thyroid with a small hypoechogenic nodule in the upper pole of the left lobe and 3 gross, almost normoechogenic nodules on the left side of the neck. On Tc-99m-pertechnetate pinhole scintigraphy there was a small, warm nodule in the upper pole of the left lobe and 3 gross metastatic nodules on the left side of the neck. Fine needle aspiration of the neck nodules was consistent with metastases from thyroid papillary carcinoma. After thyrostatic preparation a total thyroidectomy with left modified radical neck dissection was done. RESULTS AND CONCLUSION: Histopathologic examination disclosed 2 carcinomas in the left thyroid lobe. One of them was a tall cell variant of papillary carcinoma in the upper pole of the left lobe that measured 5 mm and corresponded to the small warm nodule, and the second one was a classic form of papillary microcarcinoma that measured 2 mm. Metastases accrued from the classic form of papillary microcarcinoma. Although the patient had 2 thyroid carcinomas, one with metastases and the other of more aggressive form, which is consistent with advanced stage and aggressiveness, she is now disease-free, 4 years after the operation and radioiodine ablation.

Cyclin D1 and p27 expression as prognostic factor in papillary carcinoma of thyroid: association with clinicopathological parameters.

AIM: To determine the prognostic value of cell cycle regulators cyclin D1 and p27 for papillary thyroid carcinomas. METHODS: Analysis included 180 patients with papillary thyroid carcinoma who underwent surgery at Split University Hospital Center between 1999 and 2001. Clinical data were obtained from clinical charts and histopathology reports. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue by antibody p27 and cyclin D1. Quantification was based on the intensity and distribution of nuclear staining. RESULTS: Univariate analysis showed that sex (P=0.019) and capsular invasion (P=0.010) were significant predictors of lymph node metastases, whereas age (P=0.96), histopathological variant (P=0.075), size (P=0.556) and multifocality (P=0.131) were not. Univariate analysis also showed that overexpression of cyclin D1 (P<0.001) and underexpression of p27 (P<0.001) predicted lymph node metastases in papillary thyroid carcinomas. There was a significant correlation between cyclin D1 (P=0.024) and p27 (P=0.029) expression in two prognostic groups of low and high risk. Low risk group was cyclin D1 negative and p27 positive, while high risk group was cyclin D1 positive and p27 negative. Multivariate analysis confirmed that sex (P=0.041), capsular invasion (P=0.027), and p27 (P<0.001) were strong independent predictors of lymph node metastases in the high-risk group. CONCLUSIONS: Immunohistochemical analysis of p27 expression may be a valuable tool for identifying risk of lymph node metastases and more aggressive behavior of papillary thyroid carcinoma.

Role of exfoliative cytology in diagnosis of laryngeal tumors.

OBJECTIVE: To evaluate the value of cytologic examination in the diagnosis of laryngeal tumors. STUDY DESIGN: A series of 100 patients with suspected tumorous lesions of the larynx were included in the study. The material for cytologic analysis was obtained by use of a modified instrument, that is, a slightly concave discoid knife, during direct microlaryngoscopy, followed by biopsy for paraffin and frozen section histopathology. The findings obtained by cytology and frozen section histopathology were compared with the findings of paraffin section histopathology. RESULTS: Cytology showed an 83.9% sensitivity, 100% specificity and 90% accuracy compared with histopathologic findings (p < 0.05; chi2 = 7.7). Frozen section pathohistology vs. paraffin section histopathology showed an 80.6% sensitivity, 97.4% specificity and 87% accuracy (p < 0.05; chi2 = 8.1). CONCLUSION: Cytologic examination showed higher accuracy compared to frozen section histopathology, also giving an insight into the type of laryngeal pathology in the case of precancerous lesions. The use of cytology and frozen section histopathology during direct microlaryngoscopy improves clinical diagnostic accuracy.

Anti-CD20 monoclonal antibody (Rituximab) for therapy of mediastinal CD20-positive large B-cell non-Hodgkin lymphoma with a local tumor extension into the lung of a 10-year-old girl.

Intravenous therapy with the anti-CD20 antibody Rituximab has been recently approved for the treatment of CD20 positive non-Hodgkin's lymphoma (NHL) in adults but not in children. The authors present the benefits of its application for mediastinal NHL CD 20+ with a local extension into the lung of a 10-year-old-girl. Receiving the chemotherapy according to study NHL-BFM-95 for high-risk lymphoma the girl did not reach complete remission. Before the last chemotherapy block was started, a computed tomography scan of the thorax showed residue in the right lung. Twenty-five days after the last chemotherapy she received Rituximab at a dose of 375 mg/m(2) by intravenous infusion once a week for a total of four doses without the adverse reactions. Complete remission was achieved. The patient was high risk with lung involvement of lymphoma suggesting a pure prognosis. The results suggest that Rituximab may improve the outcome in high-risk patients and appeared to be safe and effective in children also.