Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Use of Anti-Phosphohistone H3 (PHH3) as a Mitosis Marker for Classifying Pulmonary Carcinoid Tumors

  • Seo, Bo-Ram (Medical Research Center for Cancer Molecular Therapy, Dong-A University College of Medicine) ;
  • Hong, Young-Seob (Medical Research Center for Cancer Molecular Therapy, Dong-A University College of Medicine) ;
  • Choi, Phil-Jo (Department of Thoracic and Cardiovascular Surgery, Dong-A University College of Medicine) ;
  • Um, Soo-Jung (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Seo, Jeong-Wook (Prevention and Management Center, Regional Cardiocerebrovascular Center, Dong-A University Medical Center) ;
  • Roh, Mee-Sook (Medical Research Center for Cancer Molecular Therapy, Dong-A University College of Medicine)
  • Received : 2011.05.10
  • Accepted : 2011.07.18
  • Published : 2011.09.30
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Abstract

Mitosis count is one of the most helpful morphologic features for distinguishing pulmonary typical carcinoid (TC) from atypical carcinoid (AC). However, identifying areas of highest mitotic activity is tedious and time-consuming, and mitosis count may vary substantially among pathologists. Anti-phosphohistone H3 (PHH3) is an antibody that specifically detects histone H3 only when phosphorylated at serine 10 or serine 28, an event that is concurrent with mitotic chromatin condensation and not observed during apoptosis. In this study, immunohistochemical staining for PHH3 was performed to determine whether PHH3 was a reliable and objective mitosis-specific marker for pulmonary carcinoid tumors. Seventeen cases of surgically resected pulmonary carcinoid tumors (12 TCs and 5 ACs) were obtained and classified according to the 2004 World Health Organization classification. Mitotic counts determined by PHH3 correlated to ones determined by hematoxylin and eosin (H&E) staining; however, PHH3 mitotic counts (mean mitotic counts: 1 in TCs and 3.2 in ACs) were slightly higher than H&E mitotic counts (mean mitotic counts: 0.25 in TCs and 1.8 in ACs). The mitotic counts determined by experienced observer were more correlated to those determined by inexperienced observer with the PHH3-based method (R=0.968, P<0.001) rather than H&E staining (R=0.658, P<0.001). These results suggest that the PHH3 mitotic counting method was more sensitive and simple for detecting mitoses compared to traditional H&E staining. Therefore, PHH3 immunohistochemistry may contribute to more accurate and reproducible diagnosis of pulmonary carcinoid tumors and may be a valuable aid for administrating appropriate clinical treatment.

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References

  1. Baak JPA. Mitosis counting in tumors. Hum Pathol. 1990. 21: 683-685. https://doi.org/10.1016/0046-8177(90)90026-2
  2. Colman H, Giannini C, Huang L, Gonzalez J, Hess K, Bruner J, Fuller G, Langford L, Pelloski C, Aaron J, Burger P, Aldape K. Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas. Am J Surg Pathol. 2006. 30: 657-664. https://doi.org/10.1097/01.pas.0000202048.28203.25
  3. Harpole DH Jr, Feldman JM, Buchanan S, Young WG, Wolfe WG. Bronchial carcinoid tumors: a retrospective analysis of 126 patients. Ann Thorac Surg. 1992. 54: 50-54. https://doi.org/10.1016/0003-4975(92)91139-Z
  4. Hendzel MJ, Nishioka WK, Raymond Y, Allis CD, Bazett-Jones DP, Th'ng JP. Chromatin condensation is not associated with apoptosis. J Biol Chem. 1998. 273: 24470-24478. https://doi.org/10.1074/jbc.273.38.24470
  5. Kapur P, Rakheja D, Balani JP, Roy L, Amirkhan RH, Hoang MP. Phosphorylated histone H3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 expression in benign and atypical granular cell tumors. Arch Pathol Lab Med. 2007. 131: 57-64.
  6. Kim YJ, Ketter R, Steudel WI, Feiden W. Prognostic significance of the mitotic index using the mitosis marker antiphosphohistone H3 in meningiomas. Am J Clin Pathol. 2007. 128: 118-125. https://doi.org/10.1309/HXUNAG34B3CEFDU8
  7. Lee CH, Chang HK, Lee HW, Shin DH, Roh MS. The interobserver variability for diagnosing pulmonary carcinoid tumor. Korean J Pathol. 2010. 44: 267-271. https://doi.org/10.4132/KoreanJPathol.2010.44.3.267
  8. Lim E, Goldstraw P, Nicholson AG, Travis WD, Jett JR, Ferolla P, Bomanji J, Rusch VW, Asamura H, Skogseid B, Baudin E, Caplin M, Kwekkeboom D, Brambilla E, Crowley J. Proceedings of the IASLC international workshop on advances in pulmonary neuroendocrine tumors. 2007. J Thorac Oncol. 2008. 3: 1194-1201. https://doi.org/10.1097/JTO.0b013e3181861d7b
  9. Marty-Ane CH, Costes V, Pujol JL, Alauzen M, Baldet P, Mary H. Carcinoid tumors of the lung: do atypical features require aggressive management? Ann Thorac Surg. 1995. 9: 78-83.
  10. Ribalta T, McCutcheon IE, Aldape KD, Bruner JM, Fuller GN. The mitosis-specific antibody anti-phosphohistone-H3 (PHH3) facilitates rapid reliable grading of meningiomas according to WHO 2000 criteria. Am J Surg Pathol. 2004. 28: 1532 -1536. https://doi.org/10.1097/01.pas.0000141389.06925.d5
  11. Scott IS, Heath TM, Morris LS, Rushbrook SM, Bird K, Vowler SL, Arends MJ, Coleman N. A novel immunohistochemical method for estimating cell cycle phase distribution in ovarian serous neoplasms: implications for the histopathological assessment of paraffin-embedded specimens. Br J Cancer. 2004. 90: 1583-1590. https://doi.org/10.1038/sj.bjc.6601660
  12. Shibata K, Inaaki M, Ajiro K. Mitosis-specific histone H3 phsophorylation in vitro in nucleosome structures. Eur J Biochem. 1990. 192: 87-93. https://doi.org/10.1111/j.1432-1033.1990.tb19199.x
  13. Tapia C, Kutzner H, Mentzel T, Savic S, Baumhoer D, Glatz K. Two mitosis-specific antibodies, MPM-2 and phospho-histone H3 (Ser28), allow rapid and precise determination of mitotic activity. Am J Surg Pathol. 2006. 30: 83-89. https://doi.org/10.1097/01.pas.0000183572.94140.43
  14. Travis WD, Rush W, Flieder DB, Falk R, Fleming MV, Gal AA, Koss MN. Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol. 1998a. 22: 934-944. https://doi.org/10.1097/00000478-199808000-00003
  15. Travis WD, Gal AA, Colby TV, Klimstra DS, Falk R, Koss MN. Reproducibility of neuroendocrine lung tumor classification. Hum Pathol. 1998b. 29: 272-279. https://doi.org/10.1016/S0046-8177(98)90047-8
  16. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. World Health Organization Classification of Tumour. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. 2004. IARC press. Lyon, France.