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Tyrosine1248-phosphorylated HER2 expression and HER2 gene amplification in female invasive ductal carcinomas

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Abstract

Background

Phosphorylated HER2 (pHER2) may more accurately reflect the signaling and functional activity of the HER2 protein than detection of HER2 itself. The detection of HER2 gene amplification using fluorescence in situ hybridization (FISH) provides superior prognostic information for the diagnosis of breast cancer. However, the relationship between pHER2 expression in tissue samples and HER2 gene amplification remains unclear.

Methods

A total of 210 cases were recruited. The expression of HER2 and tyrosine (Tyr)1248-pHER2 was investigated by immunohistochemistry, and HER2 gene amplification was analyzed by FISH. Spearman’s rank correlation test was employed to confirm correlation between HER2 and Tyr1248-pHER2. Chi-square and Student’s t test were used to determine a significant difference between the baseline characteristics of tumors and the FISH, HER2 and Tyr1248-pHER2 results. The phosphorylation rate of HER2 was calculated using a digital-analysis system.

Results

HER2 expression was significantly (P < 0.001) associated with Tyr1248-pHER2 expression. HER2 gene amplification could be detected in 55 (26.2%) of the 210 tumors; 40 were HER2 positive and 32 were Tyr1248-pHER2 positive. The sensitivity and specificity of HER2 and Tyr1248-pHER2 for HER2 gene amplification were 72.7 and 58.2%, and 91.6 and 95.5%, respectively. In cases with an HER2 score of 2, and a phosphorylation score of 2 or 3, gene amplification was observed in 4 (80.0%) out of 5 tumors.

Conclusions

Tyr1248-pHER2 expression is highly specific for HER2 gene amplification. The phosphorylation status might provide an adjunct to the assessment of gene amplification in patients with an HER2 score of 2.

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Abbreviations

p:

Phosphorylated

FISH:

Fluorescence in situ hybridization

IHC:

Immunohistochemistry

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Authors and Affiliations

  1. Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, 737-0023, Japan

    Kiyomi Taniyama, Junichi Motoshita, Kazuya Kuraoka, Akihisa Saito & Toshinori Uike

  2. Department of Pathology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, 737-0023, Japan

    Kiyomi Taniyama, Katsunari Ishida, Tamaki Toda, Junichi Motoshita, Kazuya Kuraoka & Akihisa Saito

  3. Department of Medical Science, DakoCytomation Co. Ltd, Nishinotouin-higashiiru, Shijo-dori, Shimogyo-ku, Kyoto, 600-8493, Japan

    Yoichi Tani

  4. Department of Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, 737-0023, Japan

    Seiichi Teramoto & Masato Koseki

Authors
  1. Kiyomi Taniyama
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  2. Katsunari Ishida
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  3. Tamaki Toda
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  4. Junichi Motoshita
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  5. Kazuya Kuraoka
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  6. Akihisa Saito
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  7. Yoichi Tani
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  8. Toshinori Uike
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  9. Seiichi Teramoto
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  10. Masato Koseki
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Correspondence to Kiyomi Taniyama.

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Taniyama, K., Ishida, K., Toda, T. et al. Tyrosine1248-phosphorylated HER2 expression and HER2 gene amplification in female invasive ductal carcinomas. Breast Cancer 15, 231–240 (2008). https://doi.org/10.1007/s12282-007-0026-8

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  • DOI: https://doi.org/10.1007/s12282-007-0026-8

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