Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes

BACKGROUND: Gastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear. METHODS: MSI status was assessed in 414 cases of gastric cancer using polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed. RESULTS: Out of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (> or =2/high power field, p or =10% of mass, p=0.031), tumor-infiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p=0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197). CONCLUSIONS: Our data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.

Primary Squamous Cell Carcinoma of the Liver Initially Presenting with Pseudoachalasia

Pseudoachalasia secondary to primary squamous cell carcinoma (SCC) of the liver is extremely rare and has not been reported until now. Here, we report a unique case of primary SCC of the liver initially presenting with progressive dysphagia along with short periods of significant weight loss. A 58-year-old man initially presented with progressive dysphagia along with significant weight loss over brief periods of time. The radiographic and manometric findings were consistent with achalasia. Subsequent esophagogastroduodenoscopy revealed a moderately dilated esophagus without evidence of neoplasm or organic obstruction. However, firm resistance was encountered while traversing the esophagogastric junction (EGJ), although no mucosal lesion was identified. Due to the clinical suspicion of the presence of a malignant tumor, endoscopic ultrasonography (EUS) and computed tomography scans of the chest and abdomen were obtained. A huge hepatic mass with irregular margins extending to the EGJ was found. EUS-guided fine-needle aspiration was performed, and the mass was diagnosed as a primary SCC of the liver by immunohistochemical staining.

Primary leiomyosarcoma of gallbladder / 대한외과학회지

Malignant mesenchymalneoplasms of the gallbladder are extremely rare with only 105 cases of primary gallbladder sarcoma having been described. It has a very aggressive behavior and is usually diagnosed at advanced stages. Therefore, curative surgical management may not be possible. We performed a radical cholecystectomy (S4b + S5 segmentectomy), omentectomy and small bowel resection in a 54-year-old patient with locally invasive leiomyosarcoma of the gallbladder. Further studies are needed to confirm the benefit of aggressive treatment for patients with leiomyosarcoma of the gallbladder.

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.

Menin Mutational Analysis in a MEN I Family / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: MEN I is an autosomal dominant disorder characterized by multiple tumors occurring in the parathyroid, pituitary, and pancreas. There is a variety of mutations in MEN I that are scattered throughout the coding region, thus MEN I family has its unique type of mutations. The aim of this study is to investigate the significance of genetic screening via analyzing the MEN I gene in the MEN I family. SUBJECTS AND METHOD: Three family members related to MEN I were involved for studying the MEN I gene mutation by using single strand conformational polymorphism and DNA sequence analysis of the coding region and the exon-intron boundaries of the MEN I gene. RESULTS: A specific germline mutation of 1023 a to g transition at the splice acceptor site of exon 7 was identified in all three members of the family in the direct sequence analysis of MEN I gene. CONCLUSION: Genetic analysis for mutations in the MEN I family allows identification of individuals predisposed to the disease and enables an early diagnosis and more complete management. Also, this new diagnostic approach is helpful not only in genetic counselling of clinical management of the MEN I families but also in reducing health care expenses and psychological burden of the diseases.

Analysis of RET Gene Point Mutation in a Family with Familial Medullary Thyroid Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Hereditary medullary thyroid carcinoma is presented as a part of MEN2A (65-75%) or MEN2B, but can also be inherited alone, which is called familial medullary thyroid carcinoma. The author sought to detect point mutations of the RET proto-oncogene using the molecular genetic method on the family line of the familial medullary thyroid carcinoma, which is identified by the family history of an index patient, and to investigate the presence of point mutation carriers among the family members. SUBJECTS AND METHOD: DNA was extracted from the peripheral blood leukocyte of 5 patients who were assumed to have sporadic medullary thyroid carcinoma and 1 patient who was an index of a family line assumed to contain hereditary medullary thyroid carcinoma according to the family history. The PCR amplification of exons, 10, 11, 13, 14, 15, 16 was then carried out, and we investigated point mutations of the RET proto-oncogene using a DNA sequence analyzer. After identifying point mutation of the familial medullary carcinoma with them, the same investigation was carried out with their family. RESULTS: We identified point mutation of TGC (Cys)->CGC (Arg) at codon 618 of the RET proto-oncogene exon 10, using the automatic DNA sequence analyzing method on the index patient and detected the same point mutation with 4 of the 9 family members. Among them, the index patient and her mother who had biochemical and clinical symptoms underwent a total thyroidectomy and neck dissection and are now being followed up ; operations are scheduled for two other members later on. CONCLUSION: With the genetic analysis of RET proto-oncogene, we expect to overcome the limitations of the calcitonin stimulation test and that more complete approach through early diagnosis would be possible by carrying out the screening test for point mutation in patients with the hereditary medullary thyroid carcinoma.

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.