Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
권호 표지

Expression of Estrogen and Progesterone Receptors in Non-small-cell Lung Cancer Tissue Using Tissue Microarray Method

조직 미세배열법을 이용한 비소세포 폐암 조직에서 에스트로겐과 프로게스테론 수용체 발현

  • Han, Hye-Seung (Department of Pathology, College of Medicine, Konkuk University) ;
  • Kim, Min-Ji (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Cho, Jae-Hwa (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Yoon, Yong-Han (Department of Chest Surgery, College of Medicine, Inha University) ;
  • Kwak, Seung-Min (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Lee, Hong-Lyeol (Department of Internal Medicine, College of Medicine, Inha University) ;
  • Kim, Kwang-Ho (Department of Chest Surgery, College of Medicine, Inha University) ;
  • Ryu, Jeong-Seon (Department of Internal Medicine, College of Medicine, Inha University)
  • 한혜승 (건국대학교 의과대학 병리학교실) ;
  • 김민지 (인하대학교 의과대학 내과학교실) ;
  • 조재화 (인하대학교 의과대학 내과학교실) ;
  • 윤용한 (인하대학교 의과대학 흉부외과학교실) ;
  • 곽승민 (인하대학교 의과대학 내과학교실) ;
  • 이홍렬 (인하대학교 의과대학 내과학교실) ;
  • 김광호 (인하대학교 의과대학 흉부외과학교실) ;
  • 류정선 (인하대학교 의과대학 내과학교실)
  • Received : 2004.05.10
  • Accepted : 2004.12.09
  • Published : 2005.01.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background : To evaluate the role of estrogen and progesterone in the carcinogenesis of NSCLC, IHC studies for the expression of the receptors of estrogen and progesterone have been performed with inconsistent results. Recently the TMA method has been developed and has become recognized as a useful and rapid method for extensively analysing molecular markers at the gene and protein level. We have investigated their expressions in the tissue from NSCLC using the microarray method. Methods : The TMA construction was made with 70 formalinfixed, paraffin-embedded tissues of NSCLC. After heat-induced epitope retrieval, IHC staining on primary tissues of NSCLC was performed with the monoclonal antibodies, ER1D5 and PR1A6. Results : Our sample of 70 consisted of 74% men and 26% women. Of the patients, 49% were current smokers, 27% were non-smokers and 24% were former smokers. By histologic classification, 34 patients had squamous cell carcinoma, 24 had adenocarcinoma, 9 had adenosquamous cell carcinoma, and 3 had other carcinomas. No cancer cells were immunostained with these monoclonal antibodies in any primary tissues of NSCLC. Conclusions : No expression of neither of the two receptors was found in any of the lung cancer tissues. This suggests that adequate genetic variants for IHC staining need to be developed for NSCLC.

연구 배경 : 비소세포 폐암의 암화 과정에서 에스트로겐과 프로제스테론 단백의 역할에 대한 면역조직화학 염색을 이용한 연구들이 진행 중이다. 그러나 이 연구들은 아직 일치된 결과를 보이고 있지 않으며 이는 상용하는 면역조직화학 염색법이 한 문제로 제시되고 있다. 저자 들은 최근 새로 개발된 조직미세배열법을 이용하여 비소세포 폐암 환자의 조직에서 이들 호르몬 수용체 발현을 연구하였다. 대상 및 방법 : 대상은 70예의 비소세포 폐암 환자로 남성이 74%, 여성이 26%이었다. 이들의 포르말린 고정, 파라핀 포매조직을 이용하여 조직미세배열을 구축하였다. 가열을 통한 항체 재생 후에 폐암 조직에서 일차 단일클론 항체 (ER1D5와 PR1A6)를 이용한 면역조직화학 염색을 시행하였다. 결 과 : 흡연력은 현재 흡연자가 49%이었고, 비흡연자와 금연자는 각각 27%와 24%이었다. 폐암의 조직학적 분류는 편평상피세포암이 34예이었고, 선암, 편평상피선암, 기타 세포형은 각각 24예, 9예와 3예이었다. 단일클론 항체를 이용한 염색에서 양성 결과를 보이는 비소세포 폐암 세포는 관찰되지 않았다. 결 론 : 미세조직배열법을 이용한 에스트로겐과 프로제스테론 수용체 연구는 모든 비소세포 폐암 조직에서 음성 결과를 보였다. 현재 면역조직화학 염색에 사용되는 호르몬 수용체가 비소세포 폐암 조직에서 발현이 되지 않을 가능성을 시사해주는 소견으로 향후 적절한 항체들을 이용한 추가적인 연구가 필요하겠다.

Keywords

References

  1. Stein B, Dougherty D, Takita H, Antkowiak J, Kunz J, van Ragha D. Bronchogenic carcinoma in patients (pts) aged less than 40 years: changing demography. Proc Annu Meet Am Soc Clin Oncol 1993;12:A1141
  2. Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst 1996;88:183-92 https://doi.org/10.1093/jnci/88.3-4.183
  3. Shriver SP, Bourdeau HA, Gubish CT, Tirpak DL, Davis AL, Luketich JD, et al. Sex-specific expression of gastrin-releasing peptide receptor: relationship to smoking history and risk of lung cancer. J Natl Cancer Inst 2000;92:24-33 https://doi.org/10.1093/jnci/92.1.24
  4. Farrell PM. Fetal lung development and the influence of glucocorticoids on plmonary surfactant. J Steroid Biochem 1977;8:463-70 https://doi.org/10.1016/0022-4731(77)90248-5
  5. Mendelson CR, MacDonald PC, Johnston JM. Estrogen binding in human fetal lung tissue cytosol. Endocrinology 1980;106:368-74 https://doi.org/10.1210/endo-106-1-368
  6. Dresler CM, Fratelli C, Babb J, Everley L, Evans AA, Clapper ML. Gender differences in genetic susceptibility for lung cancer. Lung Cancer 2000;30:153-60 https://doi.org/10.1016/S0169-5002(00)00163-X
  7. Taioli E, Wynder EL. Endocrine factors and adenocarcinoma of the lung in women. J Natl Cancer Inst 1994;86:869-70 https://doi.org/10.1093/jnci/86.11.869
  8. Ollayos CW, Riordan GP, Rushin JM. Estrogen receptor detection in paraffin sections of adenocarcinoma of the colon, pancreas, and lung. Arch Pathol Lab Med 1994;118:630-2
  9. Canver CC, Memoli VA, Vanderveer PL, Dingivan CA, Mentzer RM Jr. Sex hormone receptors in nonsmall-cell lung cancer in human beings. J Thorac Cardiovasc Surg 1994;108:153-7
  10. Su JM, Hsu HK, Chang H, Lin SL, Chang HC, Huang MS, et al. Expression of estrogen and progesterone receptors in non-small-cell lung cancer: immunohistochemical study. Anticancer Res 1996;16:3803-6
  11. Vargas SO, Leslie KO, Vacek PM, Socinski MA, Weaver DL. Estrogen-receptor-related protein p29 in primary non-small cell lung carcinoma: pathologic and prognostic correlations. Cancer 1998;82:1495-500 https://doi.org/10.1002/(SICI)1097-0142(19980415)82:8<1495::AID-CNCR10>3.0.CO;2-#
  12. Omoto Y, Kobayashi Y, Nishida K, Tsuchiya E, Eguchi H, Nakagawa K, et al. Expression, function, and clinical implications of the estrogen receptor beta in human lung cancers. Biochem Biophys Res Commun 2001;285:340-7 https://doi.org/10.1006/bbrc.2001.5158
  13. di Nunno L, Larsson LG, Rinehart JJ, Beissner RS. Estrogen and progesterone receptors in non-small cell lung cancer in 248 consecutive patients who underwent surgical resection. Arch Pathol Lab Med 2000;124:1467-70
  14. Dabbs DJ, Landreneau RJ, Liu Y, Raab SS, Maley RH, Tung MY, et al. Detection of estrogen receptor by immunohistochemistry in pulmonary adenocarcinoma. Ann Thorac Surg 2002;73:403-6 https://doi.org/10.1016/S0003-4975(01)03358-6
  15. Radzikowska E, Langfort R, Giedronowicz D. Estrogen and progesterone receptors in non small cell lung cancer patients. Ann Thorac Cardiovasc Surg 2002;8:69-73
  16. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998;4:844-7 https://doi.org/10.1038/nm0798-844
  17. Bubendorf L, Nocito A, Moch H, Sauter G. Tissue microarray (TMA) technology: miniaturized pathology archives for highthroughput in situ studies. J Pathol 2001;195:72-9 https://doi.org/10.1002/path.893
  18. Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997;111:1710-7 https://doi.org/10.1378/chest.111.6.1710
  19. Kern JA, Filderman AE. Oncogenes and growth factors in human lung cancer. Clin Chest Med 1993;14:31-41
  20. Baron JA, la Vecchia C, Levi F. The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol 1990;162:502-14 https://doi.org/10.1016/0002-9378(90)90420-C
  21. Cagle PT, Mody DR, Schwartz MR. Estrogen and progesterone receptors in bronchogenic carcinoma. Cancer Res 1990;50:6632-5
  22. Werner M, Chott A, Fabiano A, Battifora H. Effect of formalin tissue fixation and processing on immunohistochemistry. Am J Surg Pathol 2000;24:1016-9 https://doi.org/10.1097/00000478-200007000-00014
  23. Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD, Christie N, et al. Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor ${\alpha}\;and\;{\beta}$ and show biological responses to estrogen. Cancer Res 2002;62:2141-50
  24. Kim WH. Tissue array method for large scale clinicopathologic study. Korean J Pathol 2002;36:199-204