Analysis of RET Gene Point Mutation in a Family with Multiple Endocrine Neoplasia Type 2A / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Multiple Endocrine Neoplasia type 2A (MEN 2A) is a syndrome that encompasses medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Since MEN 2A is inherited as autosomal dominant, early detection and treatment is crucial. A genetic analysis of RET proto-oncogene of the family members of an index patient diagnosed as MEN 2A is reported. SUBJECTS AND METHOD: A patient diagnosed as MEN 2A and his 13 family members across two generations were studied. Initially, DNA was extracted from the peripheral blood leukocyte of family members and PCR amplification of exons 10, 11, 13, 14, 15, and 16 was performed, followed by investigation of point mutation on the RET proto-oncogene using a DNA sequence analyzer. Cervical ultrasonography was carried out in the 3 nephews who were revealed to have RET proto-oncogene point mutation. RESULTS: Point mutations of TGC (cys) to TGG (Trp) at codon 634 of exon 11 at RET proto-oncogene was detected by using automatic DNA sequence analyzing method in the index patient. The same point mutation was identified in 7 of the 13 family members. Cervical ultrasonography revealed bilateral thyroid nodules in all 3 nephews who had point mutations of RET proto-oncogene. CONCLUSION: With the genetic analysis of RET proto-oncogene, limitations of the conventional calcitonin stimulation test may be overcome, and a more complete approach can be achieved through early diagnosis by carrying out this screening test for point mutations in family members of the patient with MEN 2A.

Surgical Experience of Hyperthyroidism / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: In the field of otolaryngology-head and neck surgery, surgical experience in hyperthyroidism is still limited with a lack of study on the subject. The author realized the necessity to study problems of early experience with the surgery. The purpose of this study is to elucidate significant prognostic factors in the surgery of Graves' disease and propose an optimum surgical method which is considered significant prognostic factors. SUBJECTS AND METHODS: Nineteen cases of Graves' disease and 4 cases of toxic nodule diagnosed and operated at the department of Endocrinology and department of Otolaryngology-Head and neck surgery of Kosin university Gospel Hospital, from November 1999 to February 2004 were retrospectively studied. To evaluate the safety of the surgery, preoperative management and postoperative complications were analyzed. The relations between postoperative thyroid function and surgical extent, lymphocytic infiltration, and TSH (Thyroid stimulating hormone) receptor binding inhibiting immunoglobulin were studied. Histological results of the postoperative thyroid tissue were also analyzed to detect any concurrent disease. RESULTS: Among the 9 cases of subtotal thyroidectomy in Graves' disease, 3 cases (33.3%) revealed postoperative hypothyrodism and 5 cases (55.6%) had normal thyroid function, while in 1 case (11.1%), hyperthyroidism recurred. There was no statistically significant relation between the degree of lymphocytic infiltration and postoperative thyroid function. Hyperthyroidism recurred 6 months postoperatively in one case with persistently elevated TSH receptor binding inhibiting immunoglobulin. No intraoperative or postoperative complication occurred in any of the cases. According to histopathologic results, 6 cases of Graves' disease were determined as diffuse thyroid hyperplasia and thyroid cancer was detected in 6 cases. CONCLUSION: This study revealed many advantages of surgical treatment in hyperthyroidism. High success rate and safe treatment without complication could be accomplished, and histologic diagnosis could be determined. Amounts of the remnant thyroid tissue and the level of TSH receptor binding inhibiting immunoglobulin seemed to be related to postoperative thyroid function. This study was performed with limited cases within a short period; thus, to preserve the remission state of postoperative thyroid function, studies on various factors affecting postoperative thyroid function are required.

Significance of MAGE A1-6 mRNA Expression in Sputa of the Head and Neck Cancer Patients: A Preliminary Report / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: We have reported that the expression of MAGE gene is specific to the mRNA level or protein level in head and neck cancer tissues. In this study, we investigated the applicability of MAGE gene to molecular diagnosis of head and neck cancer by detecting MAGE mRNA with common MAGE primers in sputa of patients. MATERIALS AND METHOD: Nested RT-PCR with MAGE common primers were designed by authors and were performed to detect MAGE 1, 2, 3, 4a, 4b, 5a, 5b, and 6 (MAGE A1-6) genes in sputa obtained from 22 cancer patients (17 squamous cell carcinoma of laryngopharynx, 2 lung metastsis after surgery for tongue and hypopharyngeal cancer, 2 neck metastasis from primary lung cancer, and 1 case of sarcoma of hypopharynx) and 40 normal persons. RESULTS: Of 17 sputa from squamous cell carcinoma patients, expression of MAGE mRNA was positive in 13 (76.5%) cases. MAGE was detected in 72.7% (8/11) of laryngeal cancer, 50% (1/2) of base of tongue cancer, and 100% in hypopharyngeal (2/2) and tonsillar cancer. According to T stage, T1, T2, T3, T4 was positive in 50% (2/4), 100% (5/5), 66.6% (2/3), and 80% (4/5) respectively. In case of primary lung cancer, metastatic lung cancer, and hypopharyngeal sarcoma, all expressed MAGE mRNA. Among 22 cancer patients, 81.8% (18/22) were positive. MAGE expression was detected in 5% (2/40) of the normal control. CONCLUSION: Nested RT-PCR with common MAGE primers was helpful for assessing the presence of cancer cell in the sputa of the respiratory tract. This examination can be used as a tumor marker for the screening of laryngopharyngeal cancers and early detection of recurrent cancers or lung metastasis after treatment.