Comparison of Immunohistochemical and Fluorescence In Situ Hybridization Assessment for HER-2/neu Status in Taiwanese Breast Cancer Patients

Kuo, Shou-Jen; Wang, Boris Bao-Tyan; Chang, Cheng-Shyong; Chen, Tze-Ho; Yeh, Kun-Tu; Lee, Dong-Jay; Yin, Pao-Lun; Chen, Ming

doi:10.1016/S1028-4559(07)60008-4

« Previous Next »Taiwanese Journal of Obstetrics and Gynecology
Volume 46, Issue 2 , Pages 146-151, June 2007

Comparison of Immunohistochemical and Fluorescence In Situ Hybridization Assessment for HER-2/neu Status in Taiwanese Breast Cancer Patients

Shou-Jen Kuo
- Department of Medical Research, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Surgery, National Taiwan University, and Hospital, Taipei, Taiwan
Boris Bao-Tyan Wang
- Department of Medical Research, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Center for Medical Genetics, National Taiwan University, and Hospital, Taipei, Taiwan
Cheng-Shyong Chang
- Department of Hematology-Oncology, National Taiwan University, and Hospital, Taipei, Taiwan
Tze-Ho Chen
- Department of Medical Research, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University, and Hospital, Taipei, Taiwan
Kun-Tu Yeh
- Department of Medical Research, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Pathology, Changhua Christian Hospital, Changhua, Taipei, Taiwan
Dong-Jay Lee
- Department of Medical Research, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Center for Medical Genetics, National Taiwan University, and Hospital, Taipei, Taiwan
Pao-Lun Yin
- Department of Center for Medical Genetics, National Taiwan University, and Hospital, Taipei, Taiwan
Ming Chen
- Department of Medical Research, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Center for Medical Genetics, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Obstetrics and Gynecology, National Taiwan University, and Hospital, Taipei, Taiwan
- Department of Medical Genetics, National Taiwan University, and Hospital, Taipei, Taiwan
- Correspondence to: Dr Ming Chen, Center for Medical Genetics, Changhua Christian Hospital, Changhua 500, Taiwan

Accepted 3 April 2007.

Summary

Objective

Accurate diagnostic assessment of human epidermal growth factor receptor-2 (HER-2) is essential and a prerequisite for appropriate application of the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) to the treatment of patients with breast cancer. Immunohistochemistry (IHC) is the most widely applicable diagnostic modality in studying HER-2 status. Fluorescence in situ hybridization (FISH) is also recognized as a modality in cases with an equivocal IHC status (score, 2+). Some authors claimed that FISH alone is sufficient. The aim of this study was to correlate the test results of IHC and FISH for HER-2 gene amplification in breast cancer patients. FISH for topoisomerase IIa (TOP2A) was also studied to see if deletion or amplification of TOP2A has any supplementary role to HER-2, FISH and IHC.

Materials and Methods

Assessment of HER-2 gene amplification and TOP2A gene amplification/deletion was made by FISH analysis using the LSI TOP2A/HER-2/CEP 17 multicolor probe or the LSI HER-2/CEP dual color probe (Vysis, Downers Grove, IL, USA) in formalin-fixed and paraffin-embedded tissue sections of 54 breast cancer patients who were grouped into stages 1+, 2+ or 3+ based on IHC (HercepTest; DakoCytomation, Carpinteria, CA, USA) observations.

Results

None of IHC 1+ breast tumors was HER-2 FISH positive, but three of 18 (17%) IHC 3+ tumors were HER-2 FISH negative. Overall, 53% of the IHC 2+ and 83% of the IHC 3+ cases were HER-2 FISH positive. Only one case with IHC 3+ tumor that was HER-2 FISH positive was found to have TOP2A amplification (> 2.0) and no IHC 2+ cases were found to have TOP2A amplification. There were no cases with TOP2A deletion (< 0.8) in our whole series. There were also no cases of HER-2 FISH negative tumors, but IHC scored as 2+ or 3+ (0 of 10), to be found with TOP2A amplification. The discordance rates by IHC were high (46.7% in IHC 2+, 16.7% in IHC 3+, 30.3% overall in IHC 2+ or 3+). On the contrary, the discordance rates were zero if by FISH.

Conclusion

The current algorithm to use HER-2 FISH as a supplementary role to IHC HercepTest 2+ may need some modifications according to the local setting. TOP2A FISH adds little value to HER-2 FISH and IHC staining in our study.

Key Words: breast cancer , fluorescence in situ hybridization , HER-2 , immunohistochemistry , topoisomerase IIα