갑상선 유두암에서 MHC class II 항원의 발현과 임상양상과의 관계 = The Relationship between the Expression of MHC Class II Antigens and the Clinical Prognosis of Papillary Thyroid Carcinoma Patients

다국어 초록 (Multilingual Abstract)

Background: Papillary thyroid carcinoma is among the most curable cancers, but some patients are at high risk for recurrence or even death. MHC antigens are essential molecules for the pathogenesis of carcinoma and also the physiologic immune responses against tumor. However, there is no data about the relationship between the expression of MHC antigens and the clinical prognosis of papillary thyroid carcinoma patients. Methods: We analyzed the relationship between the various prognostic factors and the MHC antigen expression by conducting a retrospective study of 215 patients, who had undergone thyroidectomy for papillary thyroid carcinoma between 1987 and 2003. Results: The expressions of MHC class II antigens were more frequent in papillary thyroid carcinoma than in the other thyroid diseases. Yet there was no statistically significant relationship between most of the clinicopathological factors and the expression of MHC class II antigens in papillary thyroid carcinoma patients. Interestingly, an HLA-DR expression was found in 8 (30.8%) of the 26 patients in the recurrence group and in 13 (76.5%) of the 17 patients in the non-recurrence group, and HLA-DP/DQ immunoreactivity was positive in 10 (38.5%) cases of the recurrence group and in 14 (82.4%) cases of the non-recurrence group. Conclusion: Papillary thyroid carcinoma showed a more frequent expression of MHC Class II antigens. However, the recurred papillary thyroid carcinoma showed a tendency to downregulate the expression of MHC class II antigens. Hence, the molecular mechanism for the expression of MHC class II antigens might have a role in the recurrence of papillary thyroid carcinoma. (J Kor Endocrinol Soc 22:26~34, 2007)

국문 초록 (Abstract)

연구배경: 갑상선 유두암은 비교적 예후가 좋은 것으로 알려져 있으나 재발을 하거나 원격전이 및 주위조직 침습을 동반하는 경우 예후가 나쁜 것으로 알려져 있다. 그러나 현재 갑상선 유두암의 예후를 예상할 수 있는 적당한 분자표지자가 없는 상태이다. MHC 항원은 갑상선암의 발생 및 진행에 대한 면역반응에 필수적인 분자로 알려져 있다. 또한 최근 진행된 연구에 의해 MHC class II 항원이 갑상선 유두암의 발암 유전자 돌연변이에 의해 발현이 증가된다는 사실이 알려졌다. 이에 저자들은 MHC class II 항원의 발현 유무와 갑상선 유두암의 임상양상의 관련성을 평가하기 위하여 본 연구를 수행하였다. 방법: 1987년부터 2003년까지 갑상선 절제술을 시행한 215명의 환자를 대상으로 의무기록 검토를 통한 임상양상 및 다양한 예후 인자들에 대한 후향적 분석을 시행하였으며 이들의 갑상선 조직에 대한 면역조직화학적 염색을 통해 MHC class II 항원의 발현 유무를 조사하였다. 추적관찰을 통해 재발 여부를 분명하게 판정할 수 있는 43명의 갑상선 유두암 환자를 선별하여 재발군과 비재발군으로 분류하였으며 두 군 간의 MHC 항원의 발현 양상에 따른 차이를 비교하였다. 결과: MHC class II 항원은 양성 질환에 비해 갑상선암에서 발현이 증가되어 있었으며 특히 갑상선 유두암에서 통계학적으로 의미 있게 발현이 증가되어 있었다. 갑상선 유두암에서 나이를 제외한 대부분의 임상적 인자 및 병리학적 인자들이 MHC class II 항원의 발현 유무에 따른 차이를 보이지 않았다. MHC class I 항원은 재발군과 비재발군 사이에서 발현 양상에 차이가 나지 않았으나 MHC class II 항원의 경우 재발군에서 발현이 억제되어 있어 비재발군과 통계학적으로 의미 있는 차이를 보였다.

참고문헌 (Reference)

1 "Tumor HLA-DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma" 115 : 231-240, 2005

2 "The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape" 53 : 904-910, 2004

3 "The relationship between MHC antigen expression and metastasis" 89-115, 1989

4 "The epidemiology of thyroid carcinoma" 25-52, 1993

5 "Structure of peptides associated with class I and class II MHC molecules" annu rev immu (annu rev immu): 181-2071994

6 "Serum thyroglobulin levels predicting recurrence and distant metastasis after surgery in patients with differentiated thyroid cancer" 18 : 153-165, 2003

7 "Regulation of signal transducer and activator of transcription 1 (STAT1) and STAT1-dependent genes by RET/PTC (rearranged in transformation/papillary thyroid carcinoma) oncogenic tyrosine kinases" 18 : 2672-2684, 2004

8 "Progress in human tumour immunology and immunotherapy" 411 : 380-384, 2001

9 "Prognostic factors for locally invasive papillary thyroid carcinomas" 59 : 478-487, 2000

10 "Modulation of the tumorigenicity of human adenovirus-12-transformed cells by interferon" 263-267, 1985

11 "Modulation of MHC antigen expression by viruses and oncogenes" immu (immu): 429-431, 1991

12 "Modification of histocompatibility antigen expression in cells expressing activated oncogene Implications for tumor development" 1161-1168, 1990

13 "Ministry of Health and Welfare Republic of Korea: 2002 annual report of the Korea Central Cancer Registry (based on registered data from 139 hospitals)" 2003

14 "Mechanisms and effects of loss of human leukocyte antigen class II expression in immune-privileged site-associated B-cell lymphoma" 12 : 2698-2705, 2006

15 "Management guidelines for patients with thyroid nodules and differentiated thyroid cancer" 16 : 109-142, 2006

16 "Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis" 34 : 1283-1289, 2003

17 "Loss of MHC class II expression is associated with a decrease of tumor-infiltrating T cells and an increase of metastatic potential of colorectal cancer: immunohistological and histopathological analyses as compared with normal colonic mucosa and adenoma" 196 : 807-815, 2000

18 "Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma" j clin endocri (j clin endocri): 960-967, 1986

19 "Immune responses to tumor antigens: implications for antigen specific immunotherapy of cancer" 54 : 669-674, 2001

20 "Expression of ras oncogene product MHC class II antigens and human papillomavirus 16/18DNA in carcinomas of the uterine cervix" 485-490, 1993

21 "Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer" 86 : 1447-1463, 2001

22 "Activation of NK cell cytotoxicity" 42 (42): 501-510, 2005

23 "A national cancer data base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995" 83 : 2638-2648, 1998