Comparison of $Na^+/I^-$ Symporter Expression Rate in Malignant and Benign Thyroid Diseases: Immunohistochemical Study

악성 및 양성 갑상선 질환의 조직에서 면역조직학적 검사법에 의한 $Na^+/I^-$ symporter의 발현율 비교

  • Kang, Do-Young (Department of Nuclear Medicine, Dong-A University College of Medicine) ;
  • Jeong, Young-Jin (Department of Nuclear Medicine, Dong-A University College of Medicine) ;
  • Lee, Kyung-Eun (Medical Research Center for Cancer Molecular Therapy, Dong-A University College of Medicine) ;
  • Park, Heon-Soo (Department of Otolaryngology-Head and Neck Surgery, Dong-A University College of Medicine) ;
  • Yoo, Young-Hyun (Medical Science Research Center, Dong-A University College of Medicine) ;
  • Roh, Mee-Sook (Medical Research Center for Cancer Molecular Therapy, Dong-A University College of Medicine)
  • 강도영 (동아대학교 의과대학 핵의학교실) ;
  • 정영진 (동아대학교 의과대학 핵의학교실) ;
  • 이경은 (동아대학교 의과대학 암분자치료연구센터) ;
  • 박헌수 (동아대학교 의과대학 이비인후과학교실) ;
  • 유영현 (동아대학교 의과대학 의과학연구소) ;
  • 노미숙 (동아대학교 의과대학 암분자치료연구센터)
  • Published : 2006.02.28

Abstract

Purpose: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. Materials and Methods: Total patients were 119 cases (Men 15, $48{\pm}13$ yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was stored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. Results: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. Conclusion: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

목적 : 기존의 연구는 갑상선 악성 종양에서 NIS 단백질 발현에 대해 충분한 증례에서 일관성 있는 결과를 보이지 못하고 있다. 이에 본 연구에서는 원발성 갑상선 악성 종양의 조직에서 NIS 발현율의 분포를 알아보고, 이를 양성 갑상선 질환에서의 NIS 발현율의 분포와 비교하였다. 대상 및 방법 : 악성 갑상선 종양이나 양성 갑상선 질환으로 수술을 시행한 환자들을 대상으로 후향적 분석을 하였다. 환자들은 총 119명(남자 15명)이며. 나이는 $48{\pm}3$세(범위 20-75세) 였다. 이들에게서 얻은 조직 표본은 총 205개 였다. 이 표본들은 악성 질환(총 153개)으로 유두상 종양이 90개, 여포상 종양이 4개, 수질상 종양이 2개, 전이성 임파절이 57개 였으며, 양성 질환(총 52개)으로 갑상선 종대가 36개, 갑상선염이 11개, 여포선종이 5개였다. 단클론 항체인 mouse anti-NIS Ab를 사용하였다. 염색된 조직을 현미경으로 관찰하여 양성 등급은 염색 강도에 따라 약하게 염색되면 등급 1, 중등도로 염색되면 등급 2, 강하게 염색되면 등급 3으로 나누었으며, 음성인 경우는 등급 0으로 표시하였다. 개개의 질환에 있어서 NIS의 발현율은 전체의 개수에 대하여 등급 2와 3이 차지하는 비율을 백분율로 표시하였다. 결과: 갑상선 악성 질환에서 NIS의 발현율은 유두상 종양의 원발성 종양에서 63%, 전이성 임파선에서 81%를 보였다. 여포상 종양과 수질상 종양의 NIS의 발현율은 각각 71, 100% 였다. 갑상선 양성 질환에서 NIS의 발현율은 갑상선 종대에서 53%, 갑상선염에서 64%, 여포선종에서 40%였다. NIS의 발현율은 악성 종양에서 양성 질환보다 더 높았다(71% vs 54%) 증례수가 많은 유두상 종양과 갑상선 종대의 경우에 한쪽 등급에만 치우침이 없이 모든 등급에 걸쳐 분포를 보이는 특징을 보였다. 갑상선 질환을 보이는 병변 조직의 주위에 있는 정상 조직의 염색 정도는 다양한 등급을 보여서 일관성을 보이지는 않았으며, 병변조직의 염색 정도와도 연관성을 보이지 않았다. 결론: 갑상선 유두상 종양에서 면역조직화학검사에 기초한 NIS의 발현율은 불균질성 분포를 나타내며 증가하는 양상을 보였고, 악성 질환과 양성 질환 사이에 NIS의 발현율이 큰 차이를 보이지 않았다.

Keywords

References

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