Assessment of the methods used to detect HER2-positive advanced extramammary Paget’s disease

Ikuko Hirai, Keiji Tanese, Yoshio Nakamura, Atsushi Otsuka, Yasuhiro Fujisawa, Yuki Yamamoto, Hiroo Hata, Taku Fujimura, Shigeto Matsushita, Koji Yoshino, Kaori Kameyama, Masayuki Amagai, Takeru Funakoshi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Article number92
JournalMedical Oncology
Issue number6
Publication statusPublished - 2018 Jun 1


  • AKT signaling pathway
  • Extramammary Paget’s disease
  • HER2
  • MAPK signaling pathway

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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