• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.139-147
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• 2001

Objectives: The most important differential point of follicular carcinoma from adenoma is capsular invasion or angioinvasion of follicular cells. Serial sections for examination of levels of tumor margins are necessary to watch the invasion. However, the interpretation of capsular invasion or angioinvasion is sometimes not feasible on the routine staining of tumor tissue. The aim of this study is to evaluate the clinical significance of expressions of $p27^{KIP1}$, MIB-1, bcl-2 and p53 in differential diagnosis of follicular adenoma and carcinoma. Materials and Methods: 16 cases of follicular carcinoma and 26 cases of follicular adenoma were entered on study of immunohistochemical stains for $p27^{KIP1}$, MIB-1, bcl-2 and p53. In carcinoma cases, correlation between the above markers, patient's age, tumor size, infiltration pattern and metastasis was studied. Results: $p27^{KIP1}$ labelling index (LI) of follicular carcinoma and adenoma was $4.89{\pm}6.92$ and $14.52{\pm}9.17$, respectively, but there was no significant difference between adenoma and carcinoma (p=0.2560). MIB-1 LI of carcinoma and adenoma was $4.11{\pm}3.89$ and $0.80{\pm}0.75$, respectively, and MIB-1 LI was significantly higher in carcinoma (p=0.0000). bcl-2 expression was seen in 2(12.5%) of 16 carcinoma cases and 130(50.0%) of 26 adenoma cases, and bcl-2 expression rate was higher in adenoma than in carcinoma(p=0.014). In one adenoma and one carcinoma case, p53 expression was noted. In follicular adenoma with atypia compared to adenoma without atypia, lower $p27^{KIP1}$ LI, higher MIB-1 LI and lower bcl-2 expression rate were seen. In follicular carcinoma, MIB-1 LI was significantly higher in invasive carcinoma(p=0.045) and was relatively increased in tumors larger than 3.0cm, showing angioinvasion and distant metastasis. But $p27^{KIP1}$ LI was higher in cases over 40 years old(p=0.008) and with conspicuous capsular invasion. There were no positive correlations between expressions of MIB-1, bcl-2 and p53. Conclusion: MIB-1 labelling index and bcl-2 expression could be helpful for differential diagnosis of follicular adenoma and carcinoma, but p53 showed very low expression rate and no significance in differential diagnosis. $p27^{KIP1}$ labelling index reveals decreasing tendency in carcinoma compared with adenoma, MIB-1 LI was considered as a poor prognostic marker in follicular carcinoma, but $p27^{KIP1}$ LI was higher in carcinoma cases over 40 years old with showing conspicuous capsular invasion. Further study for the significance of $p27^{KIP1}$ labelling index in follicular neoplasms is necessary to evaluate diagnostic value of follicular carcinoma.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.88-93
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• 1998

In order to review the clinicopathologic characteristics of the thyroid cancer associated with benign thyroid disease, we evaluated 47 patients treated between January, 1993 and September, 1997 at the Chonnam National University Hospital. In those period, we had operated a total of 690 thyroidectomy of which 320 were diagnosed as thyroid cancer. Forty three(91.4%)occurred in women and four(8.5%)occurred in men. The mean age at operation was 46.7years(range, 15 to 76 years). Forty three of the 47 cancers(91.4%) were papillary carcinomas while 4(8.5%)were follicular. Twenty four of the 47 patients (51%) were occult thyroid carcinomas measured less than 1 cm in diameter. The concurrent benign disease were nodular goiter(n=17), Hashimoto's thyroiditis(n=16), follicular adenoma(n=10), Graves' disease(n=2) and diffuse hyperplasia(n=2). Thirty one patients were diagnosed by preoperative FNAC and they underwent total thyroidectomy. Three were diagnosed by frozen section examination at the time of operation. Among them, one underwent total thyroidectomy and two underwent subtotal thyroidectomy. Eight cases revealed lymph node metastases and 2 cases extended to surrounding muscles. In conclusion, concurrent thyroid cancers and benign thyroid disease are not uncommon and a regular ultrasonic follow-up with selective aspiration cytologic examination is recommaned to enhance their diagnostic accuracy.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.94-98
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• 1998

Background: Completion thyroidectomy can most accurately be described as reexploration of the neck to remove the contralateral thyroid lobe. This procedure has commonly been performed when the histopatholoic condition of the ipsilateral thyroid lobe reveals papillary or follicular carcinoma of the thyroid. Because of a definitely increased risk of complications with completion thyroidectomy, avoiding its routine use is important. But this operation is safe procedure with minimal morbidity by coinsidering interval, surgical approach, surgeon's experience. The purpose of this review is to define the indication, and the safety of completion thyroidectomy. Materials & Methods: Recent 2 years(1995. 1 to 1996. 12), we have performed 161 thyroid operations. Fourteen of these patients were treated by completion thyroidectomy. The patients ranged in age from 21 to 66 years. We have routinely used ultrasound guided needle biopsy and intraoperative frozen section. Result: The completion thyroidectomized specimen contained papillary carcinoma in 12 (86%), follicular carcinoma in 1(7%) and follicular adenoma(no residual tumor) in 1(7%). The complication of completion thyroicetomy was absent, although case number was a few. The indication of completion thyroidectomy in our study was defined recurrence in 9 and staging in 5. The site of recurrence consists of residual thyroid in 7 and residual thyroid added cervical lymph node in 2. The staging consists of incomplete thyroidectomy 3, questionable frozen biopsy 1, and huge follicular carcinoma. Conclusion: The incidence of completion thyroidectomy appear to be increasing by application of ultrasonogram in follow-up of thyroidectomized patients, especially, for the improving of well differentiated thyroid carcinoma. Experience suggests that the morbidity of completion thyroidectomy is low, so we recommend completion thyroidectomy as an efficient and safe method of surgical treatment.

• Korean Journal of Head & Neck Oncology
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• v.21 no.1
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• pp.15-20
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• 2005

Objectives: The hepatocyte growth factor(HGF)/c-Met pathway may play various roles in the carcinogenesis of various organs. Although HGF/c-Met signalling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities, the study on their expression related to clinicopathological parameters in thyroid tumor is relatively rare. So we want to find out the clinical significance of the c-Met in thyroid tumor. Materials and Methods: We assess the mRNA and protein expression of the c-Met genes by means of RT-PCR method and the immunohistochemical stain in 100 cases of thyroid tumors(50 papillary carcinomas, 10 follicular carcinomas, 20 follicular adenomas, 20 nodular hyperplasia). Results: By RT-PCR, c-Met mRNA was detected in 43(86%) in papillary carcinoma, 4(40%) in follicular carcinoma, 4(20%) in follicular adenoma and 2(10%) in nodular hyperplasia cases. By immunohistochemistry, c-Met protein expression was detected in 44(88%), 2(20%), 3(15%) and 1(5%). Expression of the c-Met mRNA and protein expression was significantly highly recognized in papillary carcinoma. The c-Met protein overexpression was significantly correlated with the grade of the differentiation. Conclusion: These results suggest that c-Met expression may be associated with thyroid papillary cancer progression. The differential expression of c-Met protein and mRNA suggests that these molecules may be a reliable diagnostic marker in thyroid papillary cancer.

• Korean Journal of Head & Neck Oncology
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• v.13 no.1
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• pp.16-23
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• 1997

Although normal thyroid epithelial cells do not constitutively express HLA-DR antigen, their expression in wide spread within thyroid glands obtained from the human with autoimmune thyroid disease and with many neoplastic thyroids. We have, therefore, studied immunohistochemically with regard to the expression of HLA-DR antigen of thyroidectomy specimens from 50 patients of various thyroid diseases with use of paraffin-embedded tissue. One or two sections from each case were stained with commercially available mouse monoclonal antibody for class II HLA-DR antigen(HLA-DR/Alpha, DAKO) and examined by semiquantitative counting system for thyrocytes, neoplastic thyrocytes and other cells expressing HLA-DR antigen. All patients with lymphocytic thyroiditis(2/2) and diffuse hyperplasia(Graves' disease)(5/5), most patients with Hashimoto's disease(9/ll) expressed HLA-DR antigens in thyrocyte with abundant HLA-DR expressing lymphocytic infiltrates with lymph follicle formation in its vicinity or adjacent to the lesion. Most patients with papillary carcinoma(9/1l) had HLA-DR antigen detected in malignant thyrocytes ; while follicular carcinoma(0/3) and follicular adenoma(0/5) did not have detactable HLA-DR immunoreactivity. Adenomatous goiter(3/7) had HLA-DR antigen detected focally in lesser than half cases. Conversely, in four papillary carcinomas and three adenomatous goiters, HLA-DR expression of thyrocytes was found in the absence of HLA-DR expressing lymphoid infiltrates. In such cases therefore other factors more than thyroid autoimmunity must be causative for HLA-DR immunoreactivity. The results of this study indicate as follows. 1) The expression of HLA-DR on thyrocytes involved in autoimmune reactions appeared to be secondary to cytokine release from associated lymphocytic infiltrates. 2) Thyrocytes in thyroid lesions with equal degrees of lymphocytic infiltration without HLA­DR expression exhibited no HLA-DR immunoreactivity. 3) In neoplastic thyrocytes, most papillary carcinoma(9/11) exhibited detactable HLA-DR expression, while follicular carcinoma/adenoma(0/3/0/5) exhibited no detactable HLA-DR immunoreactivity which suggest the existence of divergent mechanisms inducing and modulating HLA-DR expression of different types of neoplastic thyrocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5565-5570
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• 2014

Objectives: This study aimed to characterize the histopathological pattern of thyroid lesions among Saudi patients and to highlight the age and gender variations of these lesions as base line data. Materials and Methods: We retrospectively analyzed the data from thyroid specimens received at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia from January 2006 to December 2013. Results: The 292 thyroidectomy specimens received during the study period came from 230 (78.8%) females and 62 (21.2%) males giving a female: male ratio of 3.7:1. Age of the patients ranged from 14 to 95 years with a mean age 39.7 years. Two hundred and eleven (72.3%) cases were found to be non-neoplastic and 81 (27.7%) cases were neoplastic. The non-neoplastic group included: colloid goiter, including both diffuse and nodular goiter (170 cases; 58.2%), nodular hyperplasia (28 cases; 9.6%), Hashimoto/chronic lymphocytic thyroiditis (12 cases; 4.1%), and Grave's disease (1 case; 0.3%). In neoplastic lesions, there were 7 benign tumors and 74 malignant tumors. Among the benign tumors, 5 were follicular adenomas and 2 were Hurthle cell adenomas. Papillary carcinoma was the commonest malignant tumor accounting for 87.8% of all thyroid malignancies, followed by lymphoma, follicular carcinoma and medullary carcinoma. The size of papillary carcinoma was more than 2 cm in 40 cases (76.9%). Conclusions: Non-neoplastic thyroid lesions were more common than neoplastic ones. Colloid goiter was the most common lesion. Follicular adenoma was the commonest benign tumor and papillary carcinoma was the commonest malignant lesion. There appears to be a slightly increased trend of papillary carcinoma diagnosis, most being diagnosed at an advanced stage.

• Korean Journal of Head & Neck Oncology
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• v.15 no.2
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• pp.156-161
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• 1999

Objectives: The epidermal growth factor receptor(EGFR) family has been increasingly recognized as an important component in the control of normal cell proliferation and the pathogenesis of cancer. To confirm the usefulness of epidermal growth factor receptor as a tumor marker, we initiated this study. Materials and Methods: EGFR was measured by immunohistochemical staining using EGFR antibody. It was performed on section from paraffin blocks of 65 thyroid tissue including 33 paillary carcinoma, 11 follicular carcinoma, 11 nodular hyperplasia, 5 follicular adenoma and 5 normal thyroid tissue. We evaluated morphologic characteristic of various thyroid neoplasms, and the relationship between EGFR and other prognostic factors in papillary thyroid carcinomas. Results: The expression of EGFR was commonly found in neoplasms of thyroid, with trend for stronger staining in the more malignant tumor(p=0.000). Also the expression of EGFR in papillary thyroid cancer related to tumor characters including tumor size(p=0.042), extent(p=0.024) and prognostic features including AMES scores(p=0.019). The strong EGFR staining in papillary carcinoma was significantly associated with tumor recurrence(p=0.003). Conclusions: EGFR may have a role in the regulation of normal and neoplastic thyroid cell growth. EGFR status may help predict the clinical course of patients with malignant thyroid neoplasms. However, the study of more cases will be needed for significance of the information about the EGFR as an independent prognostic factor.

• The Korean Journal of Nuclear Medicine
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• v.12 no.2
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• pp.33-40
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• 1978

Clinical features of 147 patients with biopsy-proven thyroid carcinomas were investigated from January, 1972 to April, 1978 at the Seoul National University Hospital with the following results. 1) The incidence of thyroid carcinomas according to their histopathological classification revealed 76.2% of papillary carcinoma, 19.0% of follicular carcinoma, and 3 cases of occult sclerozing carcinoma, 1 case of giant cell carcinoma and 1 case of metastatic melanoma. 2) The ratio of male to femle patients was 1:8.3 and showed no difference between papillary and follicular carcinomas. 3) The age distribution showed the peak incidence in the fourth decade (29.3%) followed by the fifth and sixth decades. 4) The average duration of illness from the onset of symptoms was about 5 years while it was 4.4 years and 7.6 years in the papillary and follicular carcinomas respectively. 5) The diameter of the thyroid masses was smaller than 5 cm in 53.6% of the patients, from 5 cm to 10 cm in 40.0% and larger than 10 cm in 6.4%. 6) In 36.4% of the patients with thyroid carcinomas the thyroid masses were fixed to adjacent tissues. 7) Metastasis to the regional lymph nodes was noted in 40.0% of the total cases, and in 45.2% and 17.6% of the papillary and follicular carcinomas respectively, while the lung and bone metastases were found in 10.0% and 4.4% in each type respectively. 8) 88.9% of the patients showed cold areas in the thyroid scans using $^{131}I$. 9) Typical psammoma bodies were observed in 21.3% of the cases in the microscopic examination of the pathological specimens. 10) The initial diagnosis of thyroid malignancy could be made before histological confirmation in 64.5% of the patients. 11) The clinical staging slightly modified from Schulz method revealed 43.6% of the patients in stage I, 26.4% in stage II, 20.9% in stags III and 9.1 % in stage IV. 12) The association with Hashimoto's thyroiditis was noted in 4 cases, with nodular goiter in 3 cases, and with follicular adenoma in 1 case.

• Korean Journal of Head & Neck Oncology
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• v.10 no.2
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• pp.200-205
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• 1994

Proliferating cell nuclear antgen(PCNA) plays an important role in DNA synthesis in nucleoli and is highly conserved non-histone nuclear protein composed of 261 amino acid. and is considered to correlated with the cells proliferative state, because it is synthesized particulary during the proliferative period of late Gland S-phase. Therefore, PCNA index meaningfully increases in the active or proliferative kinetic cells. By the use of recently developed monoclonal antibodies against PCNA, the immunohistochemical staining methods can make possible. These staining methods are the useful and productive one for ascertaining the cell's proliferating abillity. Moreover, immunohistochemical staining method with a antiPCNA antibody has particulrar advantages as follows. By means of these methods, we can stain the tissue that was already fixed in formalin or paraffin wax. We can see with naked eye that which cell is, where is differentiated through a microscope. Lastly, it maintains the whole tissue architecture and makes a search for the correlation. As we have seen above, the immunohistochemical staining methods for PCNA have been studied as an impotant factor that can find the cell proliferative kinetics in malignancy and biologic behavior of tumors. To investigate of the proliferative activity in thyroid nodule, Authors evaluated cell proliferative activity by immunostaing for PNCA in 45 pathologically confirmed solitary thyroid nodule. The results were as follows. 1) The benign nodules were 25 cases(Adenomatous Goiter: 20 cases, Follicular adenoma: 5 cases) and malignant nodules were 20 cases(Papillary Ca : 14 cases, Follicular Ca : 4 cases, Anaplastic Ca : 2 cases). 2) The Most prevalent age groups were 4th decade(11 cases), and the next group was 5th decade. 3) The average PCNA labelling indices were as follows. Adenomatous goiter(I6.9%), Follicular adenoma(37.6%), papillary Ca(26.3%), Follicular Ca(8.8%) and Anaplastic Ca(86.7%). There were no significant differences in benign(20.4) and malignant nodules (28.8%) except anaplastic Ca(p=0.3226). 4) When the average tumor size 2cm in papillary Ca, the PCNA indices were 26.0% (below 2cm) : 26.6% (above 2cm) (p=0.9642). The PCNA incidies were 23.9% (with lymphatic spread) : 28.7% (without lymphatic spread) (p=0.7056). There were no signlficant differences in the above cases. In conclusion, there were no significant differences in cell proliferative activity by staining for PCNA between benign and malignat nodules except anaplastic Ca.

• Korean Journal of Head & Neck Oncology
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• v.14 no.1
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• pp.70-75
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• 1998

Tumor growth and metastasis depends on angiogenesis. Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells in vitro and promotes neoangiogenesis in vivo. Objective: Follicular thyroid cancers(FTC) are a vascular tumor and traditionally metastasize via blood vessels. Likely other cancers, angiogenesis may playa important role in FTC. We, therefore, investigated the expression of VEGF and microvascular density by immunohistochemistry in FTC and follicular adenoma(FA). Materials and Methods: Findings of immunohistochemical stainings for VEGF and CD31 were measured by grading scale from +1 to 4+(strongest) and by counting the stained microvessels in 14 FTCs and 14 FAs. Results: 1) Expression of VEGF. a) FTCs have stronger expression than FAs in areas of tumor adjacent to capsule($mean{\pm}SD\:\;3.2{\pm}0.9\;vs\;2.0{\pm}0.9$, p<0.01) and in central area($2.3{\pm}0.7\;vs\;1.3{\pm}0.6$, p<0.01). b) The VEGF expression of capsular area in FTCs are higher than that of central area(p<0.05). 2) Microvascular density by CD31. a) FTCs have more microvessels than FAs in areas of adjacent to capsule($78.9{\pm}27.3\;vs\;38.7{\pm}15.6$, p<0.01) and in central area($75.5{\pm}23.3\;vs\;27.8{\pm}10.7$, p<0.01). b) In FTCs, the number of microvessels of capsular area are more than that of central tumor area, but not significant statistically(p>0.05). Conclusion: The higher expression of VEGF and microvascular density in FTC suggests angiogenesis plays an important role in progression of FTC.