الفهرس | Only 14 pages are availabe for public view |
Abstract Thyroid nodules are common disorder in the adult population. Most of thyroid nodules are benign and only 5-15% are malignant. Thyroid cancer represents about 2.2% of all cancers in Egypt. The initial evaluation of patients with thyroid nodules includes full detailed history, physical examination, assessing risk factors, neck ultrasonography to assess the size and suspicious characteristics, and fine needle aspiration cytology (FNAC). The gold standard definitive diagnostic tool is the postoperative histopathological examination. Fine needle aspiration cytology (FNAC) has proved to be a reliable and cost effective way to evaluate thyroid nodules. It is a main method used to evaluate and triage thyroid nodules. However, FNAC still has its technical and diagnostic limitations. Nodules classified as atypia of undetermined significance or follicular neoplasm and even those suspicious for malignancy, represent inconclusive diagnoses and may necessitate surgical intervention for excisional biopsy and postoperative histopathological examination to reach a conclusive accurate diagnosis, though many of which prove later, by postoperative biopsy, to be of benign nature. Moreover, part of FNAC limitations is related to aspiration, showing inadequate cells. In addition, FNAC is an invasive diagnostic method and depends strongly on the technical performance and competence of the operators. All the previous makes a defect in the clinical decision pathway and exerts an extra burden on patients with thyroid nodules. Therefore, more accurate and less invasive methods must be developed to add more reliable and appropriate diagnostic tools. Molecular testing platforms have been developed and are used in combination with FNAC as an essential part of the cytologic evaluation. The definitive goal of thyroid molecular analysis is to ameliorate the clinical management of patients with thyroid nodules, by accurately assessing the nature of thyroid nodules and decreasing the diagnostic uncertainty of cytologically indeterminate thyroid nodules before surgical interferance. Avoiding unnecessary diagnostic thyroid surgeries has massive implications on overall patient quality of life and cost of health care. miRNAs are endogenous small non-coding RNAs of 19 to 25 nucleotides that negatively regulates gene expression by destroying messenger RNAs (mRNAs) or preventing their translations. Several miRNAs are known to target mRNAs entangled in cancer, including those of oncogenes and tumor suppressor genes and therefore have fundamental roles in cancer establishment, progression in addition to metastasis. miRNA profiles have emerged as a noninvasive way to classify extensive types of human cancers. Due to the good stability of miRNAs in peripheral blood, the identification of miRNAs is noninvasive, sensitive and simple, which has become a hot topic in the molecular biology of tumors in recent years. Recent studies suggest that circulating miRNAs may be useful as thyroid cancer marker. The aim of the present study was to evaluate the expression of circulating miRNA 222 and miRNA 146b as a potential differentiating tool between benign and malignant thyroid nodules Summary, Conclusion and Recommendations 84 This study was conducted on 46 Egyptian adults. Subjects were categorized into 2 groups, each twenty three patients, based on microscopic pathological examination. group (I) confirmed to have malignant nodules and group (II) confirmed to have benign nodules. Both groups were subjected to full detailed medical history, clinical physical examination and ultrasonography (US) of thyroid gland and neck. Cytopathological examination of fine needle aspirate (FNA) from thyroid nodule is done for most of the cases. Plasma miRNA 222 and 146b were measured by Real time quantitative PCR. We investigated the two miRNAs (146b and 222) as possible circulating biomarkers for thyroid cancer. We compared their expression levels in plasma samples of cases with thyroid cancer and cases with benign nodules. We also analyzed the relation of their expression with thyroid ultrasound findings and the pathologic characteristics of thyroid cancer Results found a significant upregulation of plasma miRNA 222 and miRNA 146b in patients with malignant thyroid nodules compared to patients with benign thyroid nodules (p value = 0.001). This upregulation of both miRNAs showed a good diagnostic performance represented with high AUC (0.776) of ROC curve, diagnostic sensitivity (60.87%) and specificity (100 %) for miRNA 222 and, high AUC (0.825), diagnostic sensitivity (78.26%) and specificity (78.26 %) for miRNA 146b. These results denote a promising diagnostic value of circulating miRNAs 222 and 146b for identification of thyroid cancer and discriminating malignant from benign thyroid nodules. The present study revealed a significant increase of plasma miRNA 222 with vascular invasion in malignant thyroid nodules (P=0.044) that suggests a correlation between its upregulation and tumor aggressiveness. However, we found no significant relation between miRNA 146b and vascular or capsular invasion nor nodal metastasis. Combined rise of plasma miRNAs 222 and 146b, above Youden identified cutoffs, revealed a diagnostic sensitivity of 60.87 % , specificity and PPV of 100% to identify thyroid cancer and to discriminate malignant from benign thyroid nodules. We discovered also a significant additive role of plasma miRNA 222 and miRNA 146b with different ultrasound and pathological diagnostic parameters. It was found that by adding either plasma miRNA 222 or miRNA 146b to microcalcification or TIRAD 4 &5 or Bethesda class III, & IV, AUC of ROC curves increased significantly. Combining miRNAs 222 and 146b to ultrasound diagnostic parameters significantly increased the diagnostic specificity. Summary, Conclusion and Recommendations 85 6.2. Conclusion Our study found that plasma molecular biomarker miRNA 222 and miRNA 146b show promising diagnostic value for identification of thyroid cancer and discriminating malignant from benign thyroid nodules. We discovered also that plasma miRNA 222 was increased in relation to vascular invasion in malignant thyroid nodules suggesting a possible relation to tumor aggressiveness. Regarding the diagnostic performance of combined examination of circulating miRNA 222 and miRNA 146b in both studied groups, it showed a significant increase in thyroid cancer group with high specificity and positive predictive value of 100%. The present study revealed the additive diagnostic role of plasma miRNA 222 and miRNA 146b with ultrasound diagnostic parameters, microcalcification or TIRAD IV &V or Bethesda class III, & IV that could help to distinguish between benign and malignant nodules. 6.3. Recommendations Considering the evaluation of combined plasma miRNAs 222 and 146b as a potential diagnostic tool, to distinguish malignant from benign thyroid nodules to improve the accuracy of diagnosis of thyroid nodule and to reduce the number of unnecessary diagnostic thyroid surgeries aiming for a better clinical management of patients. More studies are recommended with increasing number of cases to confirm the relation between miRNA 146b and vascular or capsular invasion and nodal metastasis in malignant thyroid nodules. Evaluation of plasma miRNAs 222 and 146b in patients with recurrent thyroid cancer is recommended to assess their role in the follow up of thyroid cancer. Further studies are needed to be performed on the correlation of circulating miRNAs 222 and 146b with other genetic mutations such as, BRAF (V600E) mutation . |