Virchows Archiv

, Volume 464, Issue 5, pp 539–545 | Cite as

Interpretation of HER2 tests in gastric cancer: confirmation of interobserver differences and validation of a QA/QC educational program

  • Ryoji Kushima
  • Takeshi Kuwata
  • Takashi Yao
  • Hiroshi Kuriki
  • Kaoru Hashizume
  • Shinobu Masuda
  • Hitoshi Tsuda
  • Atsushi Ochiai
Original Article

Abstract

Accurate testing for human epidermal growth factor 2 (HER2)-positive status is now mandatory to identify gastric cancer patients that will respond to trastuzumab treatment. Immunohistochemistry testing is the primary method used in hospitals. We performed a study of diagnostic accuracy by assessing interobserver variability in immunohistochemistry scoring of HER2 and determined the effectiveness of an educational program for general pathologists that used full sections of gastric cancer specimens. A first ring study (Japanese gastric cancer [JGC] ring study) was performed by five expert pathologists, using 50 whole surgical sections selected by a coordinator, to confirm interobserver discrepancies. A second study (quality assurance/quality control program) involved administration of an educational program to 49 general pathologists that consisted of (i) comments and explanation for a set of pre-educational program cases, (ii) a lecture, and (iii) presentation of typical and special cases for discussion. Effectiveness was measured by comparing indices of the difference between scores before and after the program. The JGC ring study demonstrated good agreement in the interpretation of HER2-immunohistochemistry. Kappa coefficients among the five observers were 0.73 (substantial) and 0.84 (almost perfect) in 4 × 4 and 3 × 3 cross tests, respectively. In the second study, the concordance rate and kappa coefficients improved from pre-educational program levels of 78.6 % and 0.68, respectively, to post-educational program levels of 87.1 % and 0.79, respectively. The present results suggest that effective educational programs reduce interobserver differences between pathologists and provide optimal information regarding patient selection for treatment.

Keywords

HER2 Immunohistochemistry Gastric carcinoma Ring study Educational quality assurance/quality control program 

Notes

Acknowledgments

We thank all the pathologists who participated and cooperated in this educational program. The authors would also like to thank Dr Ludovic Croxford for providing medical writing support. This study and the medical writing support were supported by Chugai Pharmaceutical Co., Ltd. Tokyo, Japan.

Conflict of interest

RK, TK, TY, SM, HT, and AO have received honoraria for attendance at pathological advisory boards and consensus meetings from Chugai Pharmaceutical Co., Ltd. Tokyo, Japan. HK and KH are full-time employees of Chugai Pharmaceutical Co., Ltd. Tokyo, Japan.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ryoji Kushima
    • 1
    • 9
  • Takeshi Kuwata
    • 2
  • Takashi Yao
    • 3
  • Hiroshi Kuriki
    • 4
  • Kaoru Hashizume
    • 5
  • Shinobu Masuda
    • 6
  • Hitoshi Tsuda
    • 7
  • Atsushi Ochiai
    • 8
  1. 1.Department of Pathology and Clinical LaboratoriesNational Cancer Center HospitalTokyoJapan
  2. 2.Department of Pathology and Clinical LaboratoriesNational Cancer Center Hospital EastKashiwaJapan
  3. 3.Department of Human PathologyJuntendo UniversityTokyoJapan
  4. 4.Clinical Research Planning DepartmentChugai Pharmaceutical Co., Ltd.TokyoJapan
  5. 5.Medical Plan Management DepartmentChugai Pharmaceutical Co., Ltd.TokyoJapan
  6. 6.Department of PathologyNihon University School of MedicineTokyoJapan
  7. 7.Department of Basic PathologyNational Defense Medical CollegeSaitamaJapan
  8. 8.Division of PathologyResearch Center for Innovative Oncology, National Cancer Center Hospital EastKashiwaJapan
  9. 9.Department of Pathology and Clinical LaboratoriesNational Cancer Center HospitalTokyoJapan

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