Clinicopathological factors associated with HER2 status in gastric cancer: results from a prospective multicenter observational cohort study in a Japanese population (JFMC44-1101).
BACKGROUND
Human epidermal growth factor (HER) 2 positivity and its association with clinicopathological factors remain unclear in Japanese gastric cancer (GC) patients. We performed a prospective, multicenter, observational cohort study to evaluate HER2 protein expression and gene amplification in Japanese metastatic and recurrent GC patients, and explored its correlations with clinicopathological features.


METHODS
HER2 protein expression and gene amplification were centrally assessed in formalin-fixed, paraffin-embedded GC tissue by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Patient information was collected, and associations between clinicopathological factors and HER2 positivity (IHC score 3+ and/or FISH positive) and low HER2 expression (IHC score 0/FISH positive or IHC score 1+/FISH positive) were examined.


RESULTS
From September 2011 to June 2012, 1461 patients were registered across 157 sites, and the HER2 status of 1427 patients was evaluated. The rate of HER2 positivity was 21.2 %, whereas the rate of high HER2 expression (IHC score 2+/FISH positive or IHC score 3+) was 15.6 % and that of low HER2 expression was 7.0 %. Multiple logistic regression analysis identified intestinal type, absence of peritoneal metastasis, and hepatic metastasis as significant independent factors related to HER2 positivity. The intestinal type was confirmed to be the GC subtype predominantly associated with lower HER2 expression. Sampling conditions including number of biopsy samples, formalin concentration, and formalin-fixation time did not significantly affect HER2 positivity.


CONCLUSIONS
HER2 expression in Japanese patients was comparable to that in other populations examined. Intestinal type was an independent factor related to HER2 positivity and low HER2 expression.
Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Satoshi
S
Matsusaka
Department of Surgery, Niigata Prefectural Cancer Center Niigata Hospital, Niigata, Japan.
Atsushi
A
Nashimoto
Department of Surgery, Osaka General Medical Center, Osaka, Japan.
Kazuhiro
K
Nishikawa
Department of Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.
Akira
A
Miki
Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Hiroto
H
Miwa
Department of Surgical Oncology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan.
Kazuya
K
Yamaguchi
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan.
Takaki
T
Yoshikawa
Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan.
Atsushi
A
Ochiai
Kyoto University Graduate School of Medicine, Kyoto, Japan.
Satoshi
S
Morita
Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Takeshi
T
Sano
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yasuhiro
Y
Kodera
Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Japan.
Yoshihiro
Y
Kakeji
Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan.
Junichi
J
Sakamoto
Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan.
Shigetoyo
S
Saji
Department of Surgical Oncology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan. kyoshida@gifu-u.ac.jp.
Kazuhiro
K
Yoshida
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
Fluorescence in situ hybridization; Human ERBB2 protein; Immunohistochemistry; Stomach neoplasms