Chromosomal Analysis of Anaplastic Thyroid Carcinomas by Comparative Genomic Hybridization / 대한내분비학회지

BACKGROUND: Compared with common well-differentiated thyroid carcinomas, the genetic alterations underlying the development and progression of anaplastic thyroid carcinomas(ATC) are still uncharacterized. Comparative genomic hybridization(CGH) is a cytogenetic technique that can identify gains and losses in the DNA sequence copy number in tumors. METHODS: The authors studied the changes in the DNA copy number due to CGH in paraffin-embedded tissue blocks of 17 ATC cases, and tried to ascertain whether the genomic changes correlate with the clinicopathological parameters including patients' age, sex, primary tumor size, lymphovascular invasion, extrathyroid extension, regional node metastasis and immunohistochemical expression of cyclin D1. RESULTS: Fourteen of the 17 samples(82.4%) showed chromosomal changes, with a mean number of gains or losses per carcinoma of 3.6(range 2~6; 30 gains and 21 losses). The most frequently detected imbalance was the gain of chromosome 1q, which was seen in 35.7% of cases, particularly commonly in ATC associated with a papillary thyroid carcinoma. Other commonly occurring gains were present in 11q13 and 19(28.6%, respectively). Genomic amplification was detected in all four cases showing the 11q13 gain. Genomic losses were commonly noted in 3q, 6q, 18q andchi(21.4%, respectively). When numerical CGH alterations were compared to the clinicopathological parameters, there were no significant correlations(P>0.05). Cyclin D1 expression was noted in sixteen of the 17 cases(94.1%), but the extent of cyclin D1 expression was not correlated with the numerical CGH alterations(P>0.05). CONCLUSION: Taken together, the aberrations of 1q, 3q, 6q, 11q13 and 18q are relatively common in ATC, and may play an important role it developement. These findings should lead to the characterization of tumor suppressor genes and oncogenes that are potentially involved in the carcinogenesis of ATC. The amplification of 11q13 is characteristically found, but cyclin D1 in this region may be innocent of the aggressiveness of these carcinomas.

Allelotyping and Comparative Genomin Hybridization Studies in Papillary Thyroid Carcinomas and Follicular Adenomas / 대한내분비학회지

BACKGROUND: In our previous study, the prevalence of the known causes of thyroid tumorigenesis was relatively rare in Korean population, suggesting genetic and environmental differences exist. Screening of genetic alteration in papillary thyroid carcinoma(PTC) and follicular adenoma(FA) in whole genomic scale was needed prior to search on individual genes of possible causes. METHODS: Ten cases of PTC without ret/PTC-I, -2, -3 rearrangement and 5 cases of follicular adenoma were included in the study of microsatellite marker allelotyping. Sixty two microsatellite markers available, were chosen to cover the known sites of loss of heterozygosity(LOH) involved in thyroid tumors, tumor suppressor genes and terminal portion of each chromosomes. PCR was performed on tumor DNA and leukocytes DNA from each patient with MDE gel electrophoresis to detect LOH. Same specitnens as above, 3 case of normal thyroid tissues and NPA, ARO cell lines were included in the study of comparative genomic hybridization(CGH). Tumor and control DNAs were hybridized to metaphase chromosome with differential stainings with fluorescein and rhoda-mine-dUTP. Obtained results were analyzed by multicolor fluorescence computer assisted image analyzer. RESULTS: In allelotyping, LOH were detected in 5 cases of PTC, 2 cases on D10S1435, 1 case each on D2S1780, DSS1099, D11S1986, D16S539, 1 case of PTC revealed LOH on DSS1099, D11S1986. In FA, LOH were detected in 3 cases on D1S534, D1S226, Dl 1S907, D22S683, DXS9807. In CGH, Xp addition was noticed in 1 case of PTC, 12q and 10p addition was noticed in 1 case each, 16q deletion and 17q addition in 1 case of FA. CONCLUSION: No hot spot of LOH was noticed in microsatellite marker allelotyping, neither of common chromosomal change in CGH study suggesting unbalanced translocation or gene amplification more than 5-10 Mb may be involved in the genetic alteration of PTC and FA.

A Case of Biliary Papillomatosis which Underwent Curative Resection / 대한소화기내시경학회지

Biliary Papillomatosis is an extremely rare pathologic entity. Only about 40 cases of intrahepatic or diffuse intra- and extrahepatic papillomatosis have been described since the first report in 1959 by Caroli. Although this is a histologically benign lesion, its course is unfavaurable because of its tendency to extend to the entire biliary tract, high recurrence rate following local excision and the probability of progression to malignancy. We described herein a case of biliary papillomatosis associated with diffuse bile duct dilatation. The patient, a 59-year-old male, was admitted to our hospital because of right upper abdominal pain and weight loss. Cholangiogram revealed multiple round filling defects in common hepatic duct with intrahepatic bile duct dilatation. The patient underwent Whipple's operation with right lobectomy. Grossly, multiple small pin-head sized polypoid masses were seen in common bile duct, common hepatic duct and right intrahepatic duct. Microscapically, papillary epithelial hyperplasia with moderate cellular atypia was seen and there was no evidence of stromal invasion. He is healthy with a follow-up for 7 months.

The Expression of the Bcl-2 Family Proteins in Thyroid Neoplasms / 대한내분비학회지

BACKGROUND: Proteins of the Bcl-2 family are intracellular membrane-associated proteins that regulate programmed cell death either positively or negatively by as yet unknown mechanism. Bcl-2 family proteins have an antiapoptotic function, such as the Bcl-2, the long form of Bcl-x and Mcl-l, or a proapoptotic function, like the short form of Bcl-x and Bax. To investigate the potential role of Bcl-2 family proteins in thyroid tumorigenesis, the authors examined the pattern of expression of the Bel-2 family proteins in various thyroid neoplasms. METHODS: Bcl-2 family proteins, including Bcl-2, Bcl-x, Mcl-1 and Bax proteins were immunohistochemically stained in 57 cases of various thyroid neoplasms using formalin-fixed and paraffin embedded tissues; 18 cases of papillary carcinoma, 6 cases of medullary carcinoma, 4 cases of anaplastic carcinoma, 10 cases of follicular adenoma, 9 cases of adenomatous goiter, and 10 autopsy cases of fetal thyroid galnd. The intensity and frequency of the immunostaining were evaluated with the program of Image-Pro Plus Version 3.0 for image analysis. RESULT: Consistent expression of Bcl-2, Mcl-1, and Bax proteins were present in the surrounding normal thyroid tissue, however the expression of Bcl-x protein was not observed. Compare to the expression patterns of adenomatous goiter, and fetal and surrounding normal thyroid tissues, papillary and anaplastic carcinomas showed the decreased Bcl-2 and increased Bcl-x protein expressions(p (0.05). Medullary carcinoma revealed the increased Bcl-x protein expression only(p 0.05). CONCLUSION: These data suggest that combined patterns of decreased Bcl-2 and increased Bcl-x protein expressions may eontribute to the carcinogenesis of thyroid cancers originated from thyroid follicular cells, and an increased expression of Bcl-x protein may be related to the pathogenesis of medullary carcinoma from parafollicular C cells.

Prevalence of Gsa, ras, p53 Mutations and ret/PTC Rearrangement in Differentiated Thyroid Tumors of Korean Population / 대한내분비학회지

BACKGROUND: In thyroid tumor, ras, Gsa, p53 mutation and ret/FfC rearrangement have been reported with variable prevalences in different geographic regions. We studied the prevalences of these mutations and reammgement in thyroid tumors of Korean population. METHODS: Eleven cases of adenamatous goiter, 8 cases of follicular adenoma, 5 cases of foliicular carcinoma, 37 cases of papillary carcinoma were included in this study. To find mutations and rearrangement, RT-PCR, SSCP, and/or direct sequencing, after subcloning if necessary, were used. RESULTS: We could not find any rearrangment for ret/PTC-l, -2, -3 and mutations of Gsa. For ras oncogene, K and H-ras mutations were not found, but N-ras mutations, point mutation of CAA to CGA in codon 61, were detected in 1 follicular adenoma(12.5%, 1/8) and 1 follicular carcinoma(33%, 1/3). And p53 mutations were detected only in 1 case of papillary carcinoma (3%, 1/31: exon 8, codon 266 GGA-GAA). CONCLUSION: ret/PTC rearrangement, Gsa, ras and p53 mutations are relatively rare in differentiated thyroid neoplasms of Korean population, which may reflect the genetic and environmental differences from those countries with high prevalence.

A Case of Somatostatinoma which Manifested as Insulinoma when Metastasized to the Liver / 대한내분비학회지

We report a case of somatostatinoma, which manifested as insulinoma after liver metastasis. A 74-year-old man suffered from diabetes mellitus and jaundice. The abdominal CT scan of this patient showed a mass in the pancreas head, which obstructed biliary duct. He underwent Whipples procedure. Immunohistochemical staining of postoperative specimen disclosed that this tumor was strongly positive for somatostatin. After 4 months, follow up CT scan showed multiple metastatic lesions in the liver. We performed transarterial chemoinfusion two times, but the response was disappointing. After 2 months, he suffered from altered mentality, which was relieved by intake of sugar. Biochemical laboratory findings and immunohistochemical staining of liver biopsy disclosed that the metastatic lesion in this patient was insulinoma. We performed embolization of hepatic artery with gelform. The biochemical response was dramatic, but he died of septic shock, which was caused by gas forming liver abscess. In summary, we report a case of somatostatinoma which manifested as insulinoma after metastasis to the liver.

Concurrent Medullay and Papillary Carcinoma of the Thyroid / 대한내분비학회지

The origins of medullary carcinoma and papillary carcinoma of thyroid are embryologically different. We report a case of simultaneous occurrence of medullary carcinoma and papillary carcinoma of the thyroid in the same thyroid gland. In this case, the occurrence of the two tumors may be a coincidence, does not have embryological or genetical significance.

The Differential p53 Expression in Breast Cancer Development and the Correlation to Proliferative Index of Breast Cancer

p53 plays an important function as a negative regulator of cell growth and also inhibits transformation. It has been hypothesized that p53, acting as a control gene at a G1 check point, may detect DNA damage, slow the cell devision, and allow time for DNA repair. If damage is irreparable, the cell may be driven down into the apoptotic pathway, thus preventing replication of defective cells. In this retrospective study, we investigated the correlation between p53 protein expression by IHC staining and benign breast disease with or without atypical ductal hyperplasia, DCIS and invasive breast cancer. Also We analyzed the association between p53 protein expression and the following prognostic parameters in breast cancer patients; age, tumor size, axillary node involvement, stage, histologic grade, estrogen receptor, and progesteron receptor, and DNA ploidy. And, we investigated the correlation between p53 protein expression and the proliferative index of S phase fraction in diploid breast cancer. The results were as follows ; 1) In histopathological classification, none out of ten benign breast diseases, none out of seventeen fibrocystic disease with atypical ductal hyperplasia patients were p53 protein positive, 3 out of fifteen DCIS (20%), 29 out of eighty-six (34%) invasive breast cancer patients were p53 protien positive.2) There were no significant differences between p53 positivity and age, tumor size, axillary node involvement, stage, histologic grade, ER and PGR status, and DNA ploidy by Fisher's exact test with chi-squre test for trend, in invasive breast cancer. (n=86) 3) In diploid tumor (n=35), statistically significant differences were noted such that high S-phase fraction tumor revealed increased p53 positivity. (p<0.05) We have found that immunopositivity for p53 was detected in 20% of in situ carcinoma, suggesting that p53 mutation can be acquired early in malignant progression. We have also found that there is a strong direct correlation between the amount of mutant protein and tumor proliferation rate. These results are consistent with the hypothesis that wild-type p53 is involved in suppression of the cell cycle.

Two Cases of Mucinous Ductal Ectasia of the Pancreas which Showed Characteristic Pancreatoscopic Findings / 대한소화기내시경학회지

We report two cases of mucinous ductal ectasia of the pancreas which showed characteristic pancreatoscopic findings. They also showed characteristic duodenoscopic findings such as patulous ampullary orifice and mucus leakage from the papilla, and underlying pathology was hyperplasia in one case and adenoma in the other case, The insertions of pancreatoscope into the main pancreatic duct were easy without previous sphincterotomy and whitish frog egg-like mucosa was noted in one case and finger-like papillary projection was noted in the other case.

Thre Cases of Mucinous Ductal Ectasia of the Pancreas Which Were Diagnosed by Duodenoscopic Findings / 대한소화기내시경학회지

We have experienced three cases of mucinous ductal ectasia of the pancreas. They showed the characteristic duodenoscopic findings and underlying pathology was hyperplasia in two cases and adenocarcinoma in one case. When endoscopic retrograde pancreatography was performed, bulging ampulla of Vater, patulous ampullary orifice and mucus leakage from papillary orifice were noted. Also cyst-like dilatation of main duct or side branch of the uncinate process were observed.