THERAPEUTIC APPLICATION OF HISTOCHEMISTRY TO BREAST CANCERS : Trastuzumab treatment and selection of patients based on HER2 histochemistry
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概要
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Breast cancers have been treated by surgery, radiation, chemotherapy and endocrine therapy. Recently developed humanized monoclonal antibody Trastuzumab (Herceptin) has been effective for metastatic or recurrent breast cancers if the tumors show overexpressed and amplified HER2 gene. HER2 has been recognized as unfavorable prognostic factor in the breast cancers. HER2 gene is located on chromosome 17 and HER2 gene product is 185kD transmembranous protein and stimulates tyrosine kinas related transduction system. The overexpression of HER2 protein has been assessed by immunohistochemistry (IHC) and the amplification of HER2 gene has been analyzed mainly by fluorescence in situ hybridization (FISH). It has been reported that HER2 overexpression and amplification correlate with worse prognosis of the breast cancers. The Trastuzumab has been effectively used for the patients with advanced (metastatic or recurrent) breast cancers if the cancers cells overexpress HER2 protein and show amplified HER2 gene. The evaluation of HER status has been done by IHC (for overexpression) or by FISH (for gene amplification). The staining results are graded semi-quantitatively as 0(negative), 1+, 2+, 3+ according to the intensity of the HER2 staining on the cell membrane. IHC 3+ shows high concordance with FISH amplifcation, but the concordance is low between FISH and IHC 2^* which requires futher reconfirmation by FISH. Currently, the patients with HER2 IHC3+ are treated with Trastuzumab, and the patients with IHC2+ subject to FISH and are treated if FISH is positive for gene amplification. For IHC, paraffin sections of the primary or metastatic carcinoma are subjected to the staining kit, HerecpTest (DAKO) or IHC using individual monoclonal antibodies (CB11, TAB250). For FISH, double colored FISH (PathVysion) for the genes HER2 and CEP17 has been frequently used for the analysis in breast cancers. FISH is interpreted as positive if the HER2/CEP17 ratio is greater than 2.. These histochemical techniques have been approved by the Ministry of Health and Labor in JAPAN. Automated FISH(Ventata INFORM), and choromogenic ISH(CISH) using peroxidase have been also used for the analysis of HER2 gene amplification As a summary, this may represent the first modle of the application of histochemistry in "personalized" or "Tailor made" medicine highlighting the role of pathologists in the cancer therapy.
- 日本組織細胞化学会の論文
著者
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Itoh H
Department Of Pathology & Division Of Diagnostic Pathology Tokai University School Of Medicine
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ITOH Hitoshi
Department of Pathology, Tokai University School of Medicine
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Umemura Shinobu
Department Of Pathology & Division Of Diagnostic Pathology Tokai University School Of Medicine
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Osamura R.yoshiyuki
Department Of Pathology & Division Of Diagnostic Pathology Tokai University School Of Medicine
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Itoh Hitoshi
Department Of Pathology School Of Medicine Tokai University
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ITOH HITOSHI
Department of Neuropsychiatry, School of Medicine, Keio University
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