HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer

被引：30

作者：

Hosonaga, Mari ^{[1
]}

Arima, Yoshimi ^{[2
]}

Sampetrean, Oltea ^{[2
]}

Komura, Daisuke ^{[3
]}

Koya, Ikuko ^{[4
]}

Sasaki, Takashi ^{[5
]}

Sato, Eiichi ^{[6
]}

Okano, Hideyuki ^{[4
]}

Kudoh, Jun ^{[7
]}

Ishikawa, Shumpei ^{[3
]}

Saya, Hideyuki ^{[2
]}

Ishikawa, Takashi ^{[1
]}

机构：

[1] Tokyo Med Univ, Dept Breast Surg & Oncol, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan

[2] Keio Univ, Inst Adv Med Res, Div Gene Regulat, Sch Med,Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[3] Tokyo Med & Dent Univ, Med Res Inst, Dept Genom Pathol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138510, Japan

[4] Keio Univ, Dept Physiol, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[5] Keio Univ, Ctr Supercentenarian Med Res, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[6] Tokyo Med Univ, Inst Med Sci, Dept Pathol, Med Res Ctr,Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan

[7] Keio Univ, Lab Gene Med, Sch Med, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 08期

关键词：

HER2; heterogeneity; breast cancer; poor prognosis; caspase-1; GENE AMPLIFICATION; INTRATUMORAL HETEROGENEITY; CELLS; CARCINOMAS; EXPRESSION; CASPASE-1; EVOLUTION; IMPACT;

D O I：

10.3390/ijms19082158

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity has been reported in 16-36% of HER2-positive breast cancer and its clinical impact is under discussion. We examined the biological effects of HER2-heterogeneity on mouse models and analyzed metastatic brains by RNA sequence analysis. A metastatic mouse model was developed using 231-Luc (triple negative cells) and 2 HER2-positive cell lines, namely, HER2-60 and HER2-90 which showed heterogeneous and monotonous HER2 expressions, respectively. Metastatic lesions developed in 3 weeks in all the mice injected with HER2-60 cells, and in 69% of the mice injected with HER2-90 and 87.5% of the mice injected with 231-Luc. The median survival days of mice injected with 231-Luc, HER2-60, and HER2-90 cells were 29 (n = 24), 24 (n = 22) and 30 (n = 13) days, respectively. RNA sequence analysis showed that CASP-1 and its related genes were significantly downregulated in metastatic brain tumors with HER2-60 cells. The low expression of caspase-1 could be a new prognostic biomarker for early relapse in HER2-positive breast cancer.

引用

页数：12

共 50 条

[1] HER2 Heterogeneity Affects Trastuzumab Responses and Survival in Patients With HER2-Positive Metastatic Breast Cancer
Lee, Hee Jin
Seo, An Na
Kim, Eun Joo
Jang, Min Hye
Suh, Koung Jin
Ryu, Han Suk
Kim, Yu Jung
Kim, Jee Hyun
Im, Seock-Ah
Gong, Gyungyub
Jung, Kyung Hae
Park, In Ae
Park, So Yeon
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2014, 142 (06) : 755 - 766
[2] HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer
Kaito, Akio
Kuwata, Takeshi
Tokunaga, Masanori
Shitara, Kohei
Sato, Reo
Akimoto, Tetsuo
Kinoshita, Takahiro
WORLD JOURNAL OF CLINICAL CASES, 2019, 7 (15) : 1964 - 1977
[3] HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer
Akio Kaito
Takeshi Kuwata
Masanori Tokunaga
Kohei Shitara
Reo Sato
Tetsuo Akimoto
Takahiro Kinoshita
World Journal of Clinical Cases, 2019, (15) : 1964 - 1977
[4] Clinicopathologic Significance of the Intratumoral Heterogeneity of HER2 Gene Amplification in HER2-Positive Breast Cancer Patients Treated With Adjuvant Trastuzumab
Lee, Hee Jin
Kim, Joo Young
Park, So Yeon
Park, In Ah
Song, In Hye
Yu, Jong Han
Ahn, Jin-Hee
Gong, Gyungyub
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 2015, 144 (04) : 570 - 578
[5] HER2 mutation status in Japanese HER2-positive breast cancer patients
Endo, Yumi
Dong, Yu
Kondo, Naoto
Yoshimoto, Nobuyasu
Asano, Tomoko
Hato, Yukari
Nishimoto, Mayumi
Kato, Hiroyuki
Takahashi, Satoru
Nakanishi, Ryoichi
Toyama, Tatsuya
BREAST CANCER, 2016, 23 (06) : 902 - 907
[6] Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer
Maddox, Adam L.
Brehove, Matthew S.
Eliato, Kiarash R.
Saftics, Andras
Romano, Eugenia
Press, Michael F.
Mortimer, Joanne
Jones, Veronica
Schmolze, Daniel
Seewaldt, Victoria L.
Jovanovic-Talisman, Tijana
CANCERS, 2022, 14 (11)
[7] HER2 intratumoral heterogeneity is independently associated with distal metastasis and overall survival in HER2-positive breast carcinomas
Shen, Tiansheng
Nitta, Hiroaki
Wei, Lai
Parwani, Anil, V
Li, Zaibo
BREAST CANCER RESEARCH AND TREATMENT, 2020, 181 (03) : 519 - 527
[8] Understanding the spectrum of HER2 status in breast cancer: From HER2-positive to ultra-low HER2
Ahuja, Sana
Khan, Adil Aziz
Zaheer, Sufian
PATHOLOGY RESEARCH AND PRACTICE, 2024, 262
[9] Targeting HER2 heterogeneity in breast cancer
Hamilton, Erika
Shastry, Mythili
Shiller, S. Michelle
Ren, Rongqin
CANCER TREATMENT REVIEWS, 2021, 100
[10] Pathologic complete response to neoadjuvant anti-HER2 therapy is associated with HER2 immunohistochemistry score in HER2-positive early breast cancer
Chen, Hai-Long
Chen, Qiang
Deng, Yong-Chuan
MEDICINE, 2021, 100 (44)

← 1 2 3 4 5 →