PMID- 29744813 OWN - NLM STAT- MEDLINE DCOM- 20180905 LR - 20181114 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 35 IP - 6 DP - 2018 May 9 TI - Assessment of the methods used to detect HER2-positive advanced extramammary Paget's disease. PG - 92 LID - 10.1007/s12032-018-1154-z [doi] AB - The human epidermal growth factor receptor 2 (HER2) is recognized as an oncogene as well as a therapeutic target in various cancers. Certain patients with advanced extramammary Paget's disease (EMPD) have also been reported to express HER2, which is therefore considered a therapeutic target for EMPD. However, an accurate methodology to determine HER2-positive EMPD has not been established. To assess the optimal methods for detection of HER2-positive EMPD, 73 EMPD samples were analyzed by immunohistochemical (IHC) staining, fluorescence in situ hybridization (FISH), and the HER2 testing algorithm for breast cancer of the American Society of Clinical Oncology/College of American Pathologists, which combined the results of IHC staining and FISH. The results showed discordance in the rate of positive IHC staining and FISH results. While 68.6% (24/35) of the metastatic samples showed equivocal or positive IHC staining, only 37.1% (13/35) were positive by FISH. To assess the accuracy of these methods, the degree of HER2 expression detected by each method was correlated with the staining profiles of activated downstream signaling pathways involving phosphorylated p44/42 MAPK (Thr202/Tyr204) (p-ERK1/2) and phosphorylated AKT (Ser473) (p-AKT). Among 16 lymph node metastasis samples, all HER2-positive samples as determined by the testing algorithm stained positively for both p-ERK1/2 and p-AKT. On the other hand, 10-14.3% of the samples determined by FISH or IHC showed negative staining for p-ERK1/2 and p-AKT. The results showed that combining the results of IHC and FISH according to the HER2 testing algorithm is a useful method for accurately evaluating HER2-positive EMPD. FAU - Hirai, Ikuko AU - Hirai I AD - Department of Dermatology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan. FAU - Tanese, Keiji AU - Tanese K AUID- ORCID: 0000-0002-1409-6475 AD - Department of Dermatology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan. tanese@2001.jukuin.keio.ac.jp. FAU - Nakamura, Yoshio AU - Nakamura Y AD - Department of Dermatology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan. FAU - Otsuka, Atsushi AU - Otsuka A AD - Department of Dermatology, Kyoto University School of Medicine, Kyoto, Japan. FAU - Fujisawa, Yasuhiro AU - Fujisawa Y AD - Department of Dermatology, University of Tsukuba School of Medicine, Tsukuba, Japan. FAU - Yamamoto, Yuki AU - Yamamoto Y AD - Department of Dermatology, Wakayama Medical University School of Medicine, Wakayama, Japan. FAU - Hata, Hiroo AU - Hata H AD - Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan. FAU - Fujimura, Taku AU - Fujimura T AD - Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan. FAU - Matsushita, Shigeto AU - Matsushita S AD - Department of Dermato-Oncology/Dermatology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan. FAU - Yoshino, Koji AU - Yoshino K AD - Department of Dermatology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan. FAU - Kameyama, Kaori AU - Kameyama K AD - Department of Pathology, Keio University School of Medicine, Tokyo, Japan. FAU - Amagai, Masayuki AU - Amagai M AD - Department of Dermatology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan. FAU - Funakoshi, Takeru AU - Funakoshi T AD - Department of Dermatology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan. LA - eng GR - JP17lk0201063/AMED/ PT - Journal Article DEP - 20180509 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Aged MH - Aged, 80 and over MH - Algorithms MH - Female MH - Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Paget Disease, Extramammary/*enzymology/genetics/pathology MH - Receptor, ErbB-2/*biosynthesis/genetics/metabolism MH - Signal Transduction OTO - NOTNLM OT - AKT signaling pathway OT - Extramammary Paget's disease OT - HER2 OT - MAPK signaling pathway EDAT- 2018/05/11 06:00 MHDA- 2018/09/06 06:00 CRDT- 2018/05/11 06:00 PHST- 2018/04/10 00:00 [received] PHST- 2018/05/03 00:00 [accepted] PHST- 2018/05/11 06:00 [entrez] PHST- 2018/05/11 06:00 [pubmed] PHST- 2018/09/06 06:00 [medline] AID - 10.1007/s12032-018-1154-z [pii] AID - 10.1007/s12032-018-1154-z [doi] PST - epublish SO - Med Oncol. 2018 May 9;35(6):92. doi: 10.1007/s12032-018-1154-z.