Silencing of homeobox B9 is associated with down-regulation of CD56 and extrathyroidal extension of tumor in papillary thyroid carcinoma

Kim, J.H.,Kim, Y.H.,Han, J.H.,Lee, K.B.,Sheen, S.S.,Lee, J.,Soh, E.Y.,Park, T.J. W. B. Saunders Co ; Centrum Philadelphia 2012 Human pathology Vol.43 No.8

Papillary thyroid carcinoma is the most common type of thyroid malignancy, and CD56, a neural cell adhesion molecule, is typically down-regulated in almost all cases of papillary thyroid carcinoma. Homeobox B9 is a transcription factor, belongs to the products of the homeobox transcription factor gene family, and has been known to regulate transcription of CD56 and to promote tumorigenicity and metastasis in some malignancies. In this study, we investigated the expression and relation of homeobox B9 to reduced expression of CD56 in papillary thyroid carcinomas and also a relationship between their expression and clinicopathologic parameters. Therefore, we performed CD56 and homeobox B9 immunohistochemical staining on 72 papillary thyroid carcinomas and Western blotting on 31 papillary thyroid carcinomas. CD56 protein staining revealed that it was reduced or absent in 65 papillary thyroid carcinomas (90.3%) and was related to silencing of homeobox B9 (77.8%) (P = .003). The loss of homeobox B9 expression was associated with extrathyroidal extension (P = .002), pathologic stage of tumor (P = .01), and age older than 45 years (P = .032). However, the CD56 staining did not reveal any significant relationship with clinicopathologic features (P > .05). In conclusion, reduced expression of CD56 is associated with homeobox B9 in papillary thyroid carcinomas. Furthermore, silencing of homeobox B9 is more common in older age and is linked to extrathyroidal extension and advanced pathologic stage of papillary thyroid carcinoma.

A Case of Concurrent Papillary and Medullary Thyroid Carcinomas Detected as Recurrent Medullary Carcinoma after Initial Surgery for Papillary Carcinoma

안동빈,손진호,박지영 대한갑상선학회 2013 International Journal of Thyroidology Vol.6 No.1

As the prevalence of thyroid carcinoma is rapidly increasing, coexisting subtypes of thyroid carcinomas are often found. However, concurrent papillary and medullary carcinomas in the thyroid gland are extremely rare. We report the case of a 50-year-old man with co-occurrence of multiple papillary and medullary thyroid carcinomas; the latter were undetected at initial diagnosis. Sixty-three months after the initial operation performed because of papillary carcinoma diagnosis, a metastatic lymph node was detected in the left level IV region, which was revealed as medullary carcinoma. The histopathologic results from initial surgery were reviewed, and we found multiple coexisting medullary carcinomas that were not identified initially. The incidence of concurrent papillary and medullary thyroid carcinomas will continue to increase as rates of diagnosis of and surgery for thyroid carcinoma increase. Therefore, surgeons and pathologists should be aware of the possible coexistence of subtypes of thyroid carcinomas to avoid missing concurrent lesions.

한국인 갑상선 질환의 병리학적 연구 : 1095 례의 외과적 절제물을 대상으로 Based on 1095 Surgically resected specimen

박성회,지제근,이현순,이정빈,안긍환,김용일,함의근,이상국 인제대학교 1983 仁濟醫學 Vol.4 No.4

A prospective morphological study was made on 1095 thyroid specimens which were removed surgically under various diagnoses at Seoul National University Hospital during a period of 6 years from 1976 to 1981. All thyroid specimens were carefully examined grossly by 3-5mm serial cutting after fixation. Almost entire thyroid specimen was submitted for microscopic examination. Therefore microscopic slides of one specimen ranged from 4 to 106 in number. Clinical records including operation notes were also referred to confirm the diagnosis. All of the material was examined and reviewed critically by the authors and was classified according to modified WHO classification. Among 1095 surgically removed thyroids, adenomatous goiter was the most common single disease which accounted for 43% of the entire cases. It was followed by papillary carcinoma and follicular adenoma. Of the malignant tumors, papillary carcinoma was the most frequently reported tumor, accounting for 259 cases (76%) of the entire malignancy. There were also 57 follicular carcinomas, 13 anaplastic carcinomas and 7 medullary carcinomas. Characteristic ground glass nuclei and psammoma bodies were seen fairly frequently showing the incidence of 64% and 65% of papillary carcinoma respectively. However, squamous metaplasia was present in only 17% of the papillary carcinoma. There were 56 occult sclerosing carcinomas. Most of these were detected in the thyroids of adenomatous goiter. The occult sclerosing carcinoma was found in 9.2% of adenomatous goiters while it was found in only 4.3% of follicular adenomas. It was interesting to note palpation thyroiditis seen in the thyroid specimens. It was seen in 24% of the adenomatous goiters, 17% of follicular carcinomas and 14% of the papillary carcinomas.

갑상선 유두상 암종과 유두상 증식에 대한 S-100 단백 및 EMA 발현에 대한 연구

강대영,김경희,최정목,송규상,강동욱 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.2

The diagnosis of papillary carcinoma of the thyroid is readily achieved based on a defined aggregate of histopathologic features. A papillary architecture is an imporant but not pivotal component of the diagnosis. The classic nuclear features are the essential diagnostic element. However, both papillary architecture and nuclear features may be encountered in other conditions and produce problems in histopahologic interpretation. A papillary architecture may be found within a follicular or an oncocytic neoplasm of within the nodules of hyperplastic nodular goiter. Moreover, there may be scattered cells within several thyroid lesions that display some of the nuclear characteristics of papillary carcinoma. The distinction of these lesions from papillary carcinoma is important for differential diagnosis. Thus, the availability of supportive diagnosic evidence would be helpful. Immunoreactivity for S-100 and epithelial membrace antigen was investigated in 16 papillary thyroid carcinomas(PTC), including three examples of the follicular variant, 16 cases of papillary hyperplasis, 8 follicular adenomas, and 6 follicular carcinomas. The degree of reaction was rated on a four point scale: +++, most cells(>51%) have positive staining; ++, 11-50% of cells have positive staining; +, less than 10% of cells have positive staining; -, no positive staining is present. The results are summarized as follows: 1) All the papillary carcinomas showed intense nuclear and cytoplasmic expression of S-100 (+++; 7 cases, ++; 9 cases), and EMA was expressed(++; 7 cases, ++; 6 cases, +; 3 cases). 2) In the cases of papillary hperplasia, papillary foci were generally negative for S-100 and EMA(12/16 ; -). In some areas, they were focal, of weak intensity, and showed preferential apical cytoplasmic location of oncocytic change. 3) Four of eight follicular adenomas expressed S-100(++;2 cases, +; 2 cases), whereas four were completely negative. EMA was also expressed(++; 2 cases, +; 3 cases). 4) Follicular carcinoma showed variable expression of S100 and EMA Five of six follicular carcinomas expressed S-100(++; 2 cases, +; 3 cases), whereas one was negative. EMA was also expressed(++; 2 cases, +; 1 case). In conclusion, in the distinction of papilary carcinoma from papillary hyperplasia, we would recommend an initial histological appraisal, with immunohistochemical staining of S100 and EMA in difficult cases.

Evaluating the Degree of Conformity of Papillary Carcinoma and Follicular Carcinoma to the Reported Ultrasonographic Findings of Malignant Thyroid Tumor

Jeh, Su-kyoung,Jung, So Lyung,Kim, Bum Soo,Lee, Yoen Soo unknown 2007 KOREAN JOURNAL OF RADIOLOGY Vol.8 No.3

<P><B>Objective</B></P><P>We wanted to evaluate the degree of conformity of papillary carcinoma and follicular carcinoma to the reported ultrasonographic findings of malignant thyroid tumor.</P><P><B>Materials and Methods</B></P><P>Between January 2003 and December 2004, fine needle aspiration biopsy was performed in 1,036 patients with palpable and nonpalpable thyroid lesions. We retrospectively reviewed the ultrasonographic findings of patients with papillary carcinomas (n = 127) and follicular carcinomas (n = 23) that were proven by operation or fine needle aspiration biopsy. We analyzed the ultrasonographic findings of these nodules based on the reported ultrasonographic findings of malignant thyroid tumor: hypoechogenicity, a taller than wide orientation, a microlobulated or irregular margin, a thick hypoechoic rim (halo sign), microcalcification and cystic change.</P><P><B>Results</B></P><P>The echogenicity was hypoechoic in 72.4% (92/127) of the papillary carcinomas, but it was isoechoic in 65.2% (15/23) of the follicular carcinomas (<I>p</I> < 0.001). The nodule shape was tall or round in 74.1% of the papillary carcinomas, but it was flat in 72.7% of the follicular carcinomas (<I>p</I> < 0.001). The tumor margin was microlobulated or irregular in 92.9% of the papillary carcinomas and in 60.9% of the follicular carcinomas (<I>p</I> < 0.001). A hypoechoic rim was seen in 26% of the papillary carcinomas (thin rim: 13.4%, thick rim: 12.6%) and in 86.6% of the follicular carcinomas (thin rim: 39.1%, thick rim: 47.8%, <I>p</I> < 0.001). Microcalcifications were demonstrated in 33.9% of the papillary carcinomas and in none of the cases of follicular carcinoma (<I>p</I> < 0.001). A solid mass without cystic change were seen in 98.4% of the papillary carcinomas and in 82.6% of the follicular carcinomas (<I>p</I> < 0.001).</P><P><B>Conclusion</B></P><P>The previously reported ultrasonography findings of malignant thyroid tumor are in conformity with most of the papillary carcinomas, but not with follicular carcinomas. The current ultrasonographic features for thyroid malignancy should be cautiously applied as the indication for needle aspiration biopsy so that follicular carcinomas are not missed by too narrow and strict biopsy criteria.</P>

유두 갑상선암의 왈틴 양 변이의 임상병리적 특성

정종주,이용상,홍순원<SUP>1<,SUP>,강상욱,성태연,이승철,남기현,장항석,정웅윤,박정수,Jong Ju Jeong,M,D,Yong Sang Lee,M,D,Soon Won Hong,M,D,<SUP>1<,SUP>,Sang-Wook Kang,M,D,Tae Yon Sung,M,D,Seung Chul Lee,M,D,Kee-Hyun Nam,M,D,Hang-Seok 대한갑상선-내분비외과학회 2007 The Koreran journal of Endocrine Surgery Vol.7 No.4

Purpose: Warthin-like papillary carcinomawas named owing to its close histologic resemblance to a tumor encountered in salivary gland, and this tumor is a variant of papillary thyroid carcinoma. Among the variants of papillary thyroid carcinoma, the tall cell variant and diffuse sclerosing variant have more aggressive behavior than the classic papillary carcinoma. But Warthin-like papillary carcinoma arises in a background of thyroiditis and it behaves in an indolent fashion. Since then, a few case have reported in Korea. We report here on the clinicopathologic features of five cases of warthin-like papillary carcinoma. Methods: From Jan. 1996 to Feb. 2008, five patients who were diagnosed with Warthin-like papillary thyroid carcinoma at YUMC were retrospectively reviewed. Results: All 5 patients whose pathologic features were warthin-likepapillary thyroid carcinoma were women (age range: 34∼60 years). The tumor size ranged from 0.6 to 2.4 cm. 3 tumors were confined to the thyroid, but 2 tumors had invaded the strap muscles. 3 of the 5 tumors arose in a background of lymphocytic thyroditis. Central nodal metastases were identified in 2 cases. But no lateral nodal or distant metastasis had occurred. The mean duration of follow-up was 16.5 months (range: 5∼50 months). 1 patient died because of lung cancer, and there was no recurrence for the other 4 cases during the follow-up period. Conclusion: Although the long-term follow-up data on patients with Warthin-like papillary carcinoma is not available, the clinicopathologic data does not show that Warthin-like papillary carcinoma is any more aggressive than the usual papillary carcinoma. (Korean J Endocrine Surg 2007;7: 257-259)

하시모토 갑상선염의 동반 여부에 따른 갑상선 유두암의 초음파 소견

박준영,이태현,박동희 대한영상의학회 2010 대한영상의학회지 Vol.63 No.2

목적: 하시모토 갑상선염을 동반한 환자와 동반하지 않은 환자에서 발생한 갑상선 유두암의 초음파 소견을 비교하고자 한다. 대상과 방법: 갑상선 결절로 수술을 시행한 후 갑상선 유두암으로 진단받은 190명을 후향적으로 분석하였다. 하시모토 갑상선염이 동반된 유두암 환자군과 동반되지 않은 유두암 환자군의 초음파 소견을 비교하였다. 결과: 190명의 환자 중에 61명이 수술 후 하시모토 갑상선염으로 진단되었다. 하시모토 갑상선염을 동반한 유두암 환자군은 남자 3명, 여자 58명으로 여성에서 발생 빈도가 높았다(p=0.0026). 초음파 소견상 하시모토 갑상선염을 동반한 갑상선 유두암에서 거대석회화의 발생 빈도가 유의하게 높았으며(p=0.0009), 침상 경계, 현저한 저에코, 그리고 불규칙한 모양 등은 두 집단간에 유의한 차이점이 없었다. 석회화가 없는 경우 하시모토 갑상선염이 동반된 환자에서 초음파상 유두암을 발견하지 못하는 빈도가 높았다. 결론: 하시모토 갑상선염을 동반한 갑상선 유두암은 갑상선염이 없을 때보다 거대석회화가 많이 발생하며, 초음파상 석회화가 없는 경우 악성 결절을 발견하지 못하는 경우가 있기 때문에 하시모토 갑상선염이 있는 경우 세심한 검사가 필요할 것으로 생각한다. Purpose: This study was designed to compare the ultrasonographic features of papillary thyroid carcinoma with and without Hashimoto’s thyroiditis. Materials and Methods: This retrospective study included 190 patients with papillary thyroid carcinoma which was proven by neck surgery. The difference in the ultrasonographic findings between papillary thyroid carcinoma with Hashimoto’s thyroiditis and papillary thyroid carcinoma without Hashimoto’s thyroiditis were calculated statistically. Results: Hashimoto’s thyroiditis was diagnosed in 61 of 190 patients following neck surgery. The incidence of coexisting papillary thyroid carcinoma with Hashimoto’s thyroiditis was significantly higher in women (p=0.0026). In addition, the frequency of macrocalcification in patients with Hashimoto’s thyroiditis was also significantly higher (p=0.0009). Conversely,other ultrasonographic findings including the shape, margin, echogenicity and calcifications, for patients with papillary thyroid carcinoma with Hashimoto’s thyroiditis and papillary thyroid carcinoma without Hashimoto’s thyroiditis, were not statistically significant. We also found that patients with Hashimoto’s thyroiditis who showed no calcification on ultrasonography tended not to detect the papillary carcinoma at a higher frequency. Conclusion: On ultrasonography, macrocalcifications occurred more frequently in patients with Hashimoto’s thyroiditis than those without Hashimoto’s thyroiditis. Malignant thyroid nodules without calcifications in patients with Hashimoto’s thyroiditis more often could not be detected. Therefore, it is important carefully examine patients with Hashimoto’s thyroiditis.

한국인의 갑상선 질환에서 RET 유전자 발현

이시훈,홍순원,문우철,오명열,이진경,안철우,차봉수,김경래,임승길,이현철 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.2

연구배경: RET 유전자는 제10번 염색체의 장완에 위치하는 전암유전자로서 갑상선 종양의 발생과 관련해서 두가지의 활성화 기전이 알려져 있는데, 하나는 RET/PTC 유전자 재배열로 갑상선 유두암의 발생과 연관이 있으며, 다른 하나는 점돌연변이로 갑상선 수질암과 연관이 있다. 한편 갑상선 유두암에서 RET의발현증가가 중요하다는 의견도 있으며, 한국인의 경우이에 대한 자료는 드물다. 이에 한국인의 갑상선 유두암을 비롯한 갑상선 질환에서 RET/PTC 유전자 재배열과 RET 유전자의 발현에 대해서 조사하였다. 방법: 병리 소견상 갑상선 유두암으로 진단된 27예, 갑상선 여포암 3예, 미분화암 1예, 선종 5예, 과증식 19예, 정상 소견 2예의 갑상선 조직을 대상으로 하여 RT-PCR 및 염기서열분석법을 이용하여 RET/PTC-1,-2, -3 유전자 재배열과 RET 유전자의 발현도를 조사하였고, 한편 면역조직화학 방법을 이용하여 ret 단백질의 발현을 검색하였다. 결과: RT-PCR분석 결과 갑상선 유두암중60.0%에서 RET 유전자가 검출되었고, 갑상선 여포암에서 100%, 과증식에서는 25.0%에서 RET 유전자가 검출되었으나, 미분화암, 선종, 정상 조직에서는 검출되지 않았다. 갑상선 유두암 2예에서 RET/PTC-1 재배열과RET/PTC-2 재배열이 한차례 관찰되었으나, RET/PTC-3 유전자의 재배열은 전혀 발견되지 않았다. 면역조직화학염색에서는 갑상선 유두암중 73.1%, 선종중 50%, 과증식 중 14.3%에서 RET가 강하게 발현되었으나, 정상 갑상선조직과 갑상선 여포암, 미분화암에서는 발현되지 않았다. RET의 발현 검색에 있어 RT-PCR 방법과 면역조직화학간에는 비교적 높은 일치도를 보였고, 하시모토 갑상선염에 해당하는 조직 14예 중 9예에서 ret 단백질이 강하게 발현되었다. 결론: 한국인의 갑상선 유두암에서는 RET/PTC 재배열은 드문 반면, RET 유전자의 과잉발현이 높은 빈도로 나타난다. RET의 과잉발현은 빈도가 낮긴 하나갑상선 유두암 뿐 아니라 선종과 과증식에서도 나타날 수 있다 이러한 결과는 RET의 과잉발현이 한국인의 갑상선유두암의 발병에 있어 중요한 원인이며, 지표가 될 수도 있음을 시사한다. Background: Activation of the RET proto-oncogene, located on the long arms of chromosome 10, contributes to the development of thyroid cancers in two different ways. Somatic rearrangements of RET with variable genes of activation are frequently found in papillary thyroid carcinomas. And Ggerm-line point mutations are responsible for the development of medullary thyroid carcinoma and the multiple endocrine neoplasia type 2 (MEN2). There are several conflicting reports on the influences of RET expression and RET/TTC rearrangements on the clinical outcome of thyroid cancer. Therefore, we performed an examination of RET expression and RET/TTC-1, -2, -3 rearrangements in papillary thyroid carcinomas and other thyroid diseases. Methods: Twenty-six papillary thyroid carcinomas (PTCs), three follicular thyroid carcinomas (FTCs), one anaplastic thyroid carcinoma (ATC), five follicular adenomas (FAs), nineteen hyper- plasias, and two normal thyroid tissues were included in this study. RT-PCR and immunohistochemistry analysis were done to identify RET gene, RET/TTC rearrangements, and ret RET protein expression. Results: By RT-PCR, 89.4% of PTCs, 100% of F K s , and 62.1% of hyperplasias expressed the RET gene, but no RET was observed in ATCs, FAs, and normal thyroid tissues. RETmC-1, -2, -3 rearrangements were not detected in any specimens. Immunohistochemical results revealed that 76.9% of PTCs, 50% of FAs, 52.3% of hyperplasias, and 20.6% of normal thyroid tissues expressed the RET ret protein, but lTCs and ATCs did not. Most PTCs showed strong cytoplasmic positivity in RET ret immunostaining, but the positive non- PTCs expressed weak and membranous staining. Overall, the two methods for detecting RET gene, RT-PCR and immunohistochemistry showed similar results. Conclusion: The RET gene was highly expressed in PTCs. In contrast to the previous reports of that theRET gene expression of RET gene is being limited to PTCs, RET was also expressed in hyperplasias, Fas, and normal thyroid tissues. However, the pattern and the degree of expression of the RET ret protein in non- PTCs were are different from those in PTCs (J Kor SOC Endocrinol 18: 140-152, 2003).

갑상선 유두암 환자에서 경부 림프절 재발에 대한 최소 갑상선외 침습의 임상적 중요성

황성배(Seong-Bae Hwang),류우상(Woo-Sang Ryu),서우형(U-Hyoung Seo),이재복(Jea-Bok Lee),배정원(Jung-Won Bae),구범환(Bum-Hwan Koo) 대한외과학회 2007 Annals of Surgical Treatment and Research(ASRT) Vol.73 No.5

Purpose: Extra-thyroidal extension has been recognized as a poor prognostic factor for increased regional recurrence risk in papillary thyroid carcinoma, and is known to require treatment that is more aggressive. In the recent UICC TNM 6th Classification, an extra-thyroidal extension was divided into a minimal extra-thyroidal extension (T3) and a massive extra-thyroidal extension (T4). The aim of this study was to investigate the clinical effect of a minimal extra-thyroidal extension of a papillary carcinoma for the recurrence of regional cervical lymph nodes. Methods: We retrospectively studied 154 patients with papillary thyroid carcinoma where a thyroidectomy was performed from Feb. 2003 to May. 2006 at the Department of Surgery, with the exclusion of 6 patients with a massive extra-thyroidal extension. We divided the cases into a no extra-thyroidal extension group and a minimal extra-thyroidal extension group according to the grading of the extra-thyroidal extension. The grading of the extra-thyroidal extension was based on both pathological findings and intraoperative surgical findings. Clinicopathological factors associated with each group were analyzed by univariate and multivariate analysis. We divided the cases into two groups according to age (<45 yrs, ≥45 yrs) and lymph node status (positive, negative), and compared each group with regards to disease free survival according to the grading of the extra-thyroidal extension. Results: By univariate analysis, a minimal extra-thyroidal extension was related to lymph node metastasis, tumor size, mutifocality (P<0.05), and was not related to cervical lymph node recurrence statistically (P=0.108). Cervical lymph node recurrence was related to being male, lymph node metastasis and tumor size (P<0.05). By multivariate analysis, a minimal extra-thyroidal extension was independently related to tumor size, multifocality, and lymph node metastasis (P<0.05). In both groups with regards to age and lymph node status, a minimal extra-thyroidal extension was not statistically related to disease free survival (P>0.05). Conclusion: We need to downstage to less than T3 for a minimal extra-thyroidal extension because there is no significant difference in disease free survival according to the grading of an extra-thyroidal extension in patients with papillary thyroid carcinoma.

Correlation of Expression of p53, Cylcin D1 and Galectin-3 in Papillary Carcinoma and Follicular Carcinoma

Back, Oun-Cheol 대한임상검사과학회 2013 대한임상검사과학회지(KJCLS) Vol.45 No.1

The thyroid is the organ that has the greatest risk of malignant tumors among the endocrine tumors. The papillary carcinoma occupies 80% of the entire thyroid tumors. Immunohistochemical staining of galectin-3 has usually been used in differentiating papillary carcinoma and follicular carcinoma. The p53 gene of the cell cycle is a tumor suppressor gene acting in on the control points. The cyclin D1 genes in the cell cycle, involved in the implementation of G1 and S phase, plays an important role in the progression of thyroid tumors. This research compares and analyzes correlation between papillary carcinoma, follicular carcinoma, p53, cyclin D1 and galectin-3 gene expression patterns. In a total of 30 cases from papillary carcinoma, 21 cases from p53 (70%), 27 cases in galectin-3 (90%), and 26 cases in cyclin D1 (86.7%) showed positive rate. The galectin-3 staining investigated, showed a significant difference between a papillary carcinoma and a follicular carcinoma. Follicular carcinoma from 15 cases, p53 in 13 cases (86.7%), galectin-3 in 5 cases (33.3%) and cyclin D1 in 12 cases (80%) showed a positive rate. The cyclin D1 in follicular carcinoma and staining between the p53 that had correlation was also investigated. In this study, as the examples of the expression of the 27 cases of galectin-3 (90%) in papillary carcinoma and 5 cases in follicular carcinoma (33.3%) indicate, it was concluded that there is a difference in the expression on both carcinoma. In addition, cyclin D1 and p53 has a positive rate in follicular carcinoma, when cyclin D1 in 12 cases (80%), there was a significant correlation that was investigated. Distinguishing between papillary carcinoma and follicular carcinoma can be identified by the expression of galectin-3. It is considered to get results that are more accurate in follicular carcinoma diagnosis depending on whether the cyclin D1 and p53 is expressed or not.