Diagnostic tool for diagnosing benign versus malignant thyroid lesions
Inventors
Zeiger, Martha Allen • Prasad, Nijaguna B. • Libutti, Steven K. • Umbricht, Christopher B.
Assignees
Johns Hopkins University • US Department of Health and Human Services
Publication Number
US-9234244-B2
Publication Date
2016-01-12
Expiration Date
2028-08-27
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Abstract
The present invention relates to the use of genes differentially expressed in benign thyroid lesions and malignant thyroid lesions for the diagnosis and staging of thyroid cancer.
Core Innovation
The invention relates to the use of genes differentially expressed in benign thyroid lesions and malignant thyroid lesions for the diagnosis, staging, and treatment of thyroid cancer. Specifically, it identifies a group of differentially expressed thyroid genes (DET genes) whose expression levels correlate with benign or malignant states in thyroid cells, enabling a molecular classification system for thyroid tumors. This allows for more accurate diagnosis compared to traditional histopathological methods.
The problem addressed is the difficulty in definitively diagnosing thyroid nodules as benign or malignant based on current methods such as fine needle aspiration biopsy (FNA), which often yields indeterminate or suspicious results in 10-25% of cases. This uncertainty complicates surgical decisions and can lead to unnecessary thyroidectomy or the need for multiple surgeries. Existing classification based on cellular architecture and cytology is limited, and there has been no significant improvement in diagnostic accuracy using FNA in the last few decades. Therefore, there is a compelling need for more accurate initial diagnostic tests for evaluating thyroid nodules.
The invention overcomes these diagnostic limitations by providing methods that measure expression levels of specific nucleic acid sequences of DET genes in a test cell population from a thyroid lesion, comparing these with reference cell populations of known classification. Differences in expression profiles allow classifying the lesion as benign or malignant with high accuracy. Moreover, methods are provided to identify the stage of thyroid tumors and to identify agents for treating thyroid tumors based on changes in these gene expression profiles.
Claims Coverage
The patent contains one independent claim focused on a diagnostic and treatment method involving gene expression analysis of specific thyroid cancer-related genes.
Method of diagnosing thyroid tumors using gene expression levels
A method comprising obtaining a tumor sample, measuring expression levels of HMGA2, MRC2, and SFN genes by quantitative RT-PCR, comparing these levels to reference expression levels in benign and malignant thyroid tumors, classifying the tumor as benign or malignant based on that comparison.
Treatment decision based on molecular diagnosis
Decision to treat the patient with surgical thyroid lobectomy if the tumor is benign or total thyroidectomy if malignant based on the gene expression classification.
Combination of molecular diagnosis with additional treatments
Optional treatment of the patient with anti-cancer therapy including surgery, chemotherapy, radiotherapy, immunotherapy, or any combination thereof following molecular classification.
Application to diverse thyroid tumor types
The method applies to tumors including papillary thyroid carcinoma, follicular variant of papillary thyroid carcinoma, follicular carcinoma, Hurthle cell tumor, anaplastic thyroid cancer, medullary thyroid cancer, thyroid lymphoma, poorly differentiated thyroid cancer, and thyroid angiosarcoma as well as benign lesions such as follicular adenoma, adenomatoid nodule, Hurthle cell adenoma, lymphocytic thyroiditis nodule, hyperplastic nodule, papillary adenoma, thyroiditis nodule, and multinodular goiter.
Integration with fine needle aspiration biopsy
The method can be applied where fine needle aspiration biopsy identifies indeterminate or suspicious thyroid lesions to improve diagnosis and treatment planning.
The claims cover a diagnostic method for classifying thyroid tumors as benign or malignant by evaluating expression levels of specific genes, primarily HMGA2, MRC2, and SFN, combined with treatment decision-making based on these classifications, applicable across various thyroid tumor subtypes and integrated with existing clinical procedures like FNA biopsy.
Stated Advantages
Provides a molecular classification system for thyroid tumors enabling more accurate diagnosis than current histopathological methods.
Improves the ability to distinguish benign from malignant thyroid lesions, especially in cases with indeterminate or suspicious fine needle aspiration biopsy results.
Enables more informed surgical decisions, potentially reducing unnecessary surgeries and the need for multiple operations.
Allows for the identification of tumor staging and prognosis, thus aiding clinical management.
Facilitates the identification of therapeutic agents effective for treating thyroid tumors by monitoring changes in gene expression.
The diagnostic method based on gene expression is robust, reproducible, and can be performed using standard molecular biology techniques such as RT-PCR.
Documented Applications
Diagnosis and staging of thyroid cancer by measuring differential expression of DET genes in thyroid tissue samples.
Classification of thyroid lesions as benign or malignant, including tumor subtypes such as papillary thyroid carcinoma, follicular variant of papillary thyroid carcinoma, follicular carcinoma, Hurthle cell tumors, and benign nodules.
Guiding therapeutic decisions including surgical interventions based on molecular diagnosis results.
Use as an adjunct to fine needle aspiration biopsy to improve diagnosis in indeterminate or suspicious cases.
Screening for agents that modulate expression of DET genes to identify potential treatments for thyroid tumors.
Prognostic evaluation of patients with thyroid tumors based on gene expression profiles.
Use in preparation of diagnostic kits comprising primers, probes, and antibodies for detection of DET gene expression.
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