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Original Articles
Prognostic Significance of Heat Shock Protein 70 Expression in Early Gastric Carcinoma
Youngran Kang, Woon Yong Jung, Hyunjoo Lee, Wonkyung Jung, Eunjung Lee, Bong Kyung Shin, Aeree Kim, Han Kyeom Kim, Baek-hui Kim
Korean J Pathol. 2013;47(3):219-226.   Published online June 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.219
  • 7,701 View
  • 33 Download
  • 8 Crossref
AbstractAbstract PDF
Background

Overexpression of heat shock protein 70 (HSP70) has been observed in many types of cancer including gastric adenocarcinomas, although the exact role of HSP70 in carcinogenesis remains unclear.

Methods

The study analyzed a total of 458 radical gastrectomy specimens which were immunohistochemically stained with HSP70, p53, and Ki-67 antibodies.

Results

The study determined that the expression of HSP70 was significantly increased in early gastric cancer (EGC) compared to advanced gastric cancer (p<0.001). The HSP70 expression was correlated with well-differentiated tumor type, intestinal type of Lauren classification and the lower pT and pN stage. Negative expression of Ki-67 and p53 expression was associated with poor prognosis. The study did not find any correlation between HSP70 and p53 expression. The study determined that HSP70 expression in the EGC subgroup was associated with a poor prognosis (p=0.009), as well as negative Ki-67 expression (p=0.006), but was not associated with p53. Based on multivariate analysis, HSP70 expression (p=0.024), negative expression of Ki-67, invasion depth and lymph node metastasis were determined to be independent prognostic markers.

Conclusions

HSP70 is expressed in the early stages of gastric adenocarcinoma. In EGC, HSP70 is a poor independent prognostic marker and is correlated with a low proliferation index.

Citations

Citations to this article as recorded by  
  • The Prognostic Importance of Ki-67 in Gastrointestinal Carcinomas: A Meta-analysis and Multi-omics Approach
    Mahdieh Razmi, Fatemeh Tajik, Farideh Hashemi, Ayna Yazdanpanah, Fatemeh Hashemi-Niasari, Adeleh Divsalar
    Journal of Gastrointestinal Cancer.2024;[Epub]     CrossRef
  • Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis
    Xiaolu Wang, Li Xie, Lijing Zhu
    BMC Gastroenterology.2021;[Epub]     CrossRef
  • Beta-sheet-specific interactions with heat shock proteins define a mechanism of delayed tumor cell death in response to HAMLET
    Aftab Nadeem, James C.S. Ho, Tuan Hiep Tran, Sanchari Paul, Victoria Granqvist, Nadege Despretz, Catharina Svanborg
    Journal of Molecular Biology.2019; 431(14): 2612.     CrossRef
  • Evolving paradigms on the interplay of mitochondrial Hsp70 chaperone system in cell survival and senescence
    Shubhi Srivastava, Vinaya Vishwanathan, Abhijit Birje, Devanjan Sinha, Patrick D’Silva
    Critical Reviews in Biochemistry and Molecular Biology.2019; 54(6): 517.     CrossRef
  • Clinicopathologic significance and prognostic value of Ki-67 expression in patients with gastric cancer: a meta-analysis
    Guanying Luo, Yunzhao Hu, Zhiqiao Zhang, Peng Wang, Zhaowen Luo, Jinxin Lin, Canchang Cheng, You Yang
    Oncotarget.2017; 8(30): 50273.     CrossRef
  • Extracellular HSP70-peptide complexes promote the proliferation of hepatocellular carcinoma cells via TLR2/4/JNK1/2MAPK pathway
    Yi Zhe, Yan Li, Dan Liu, Dong-Ming Su, Jin-Gang Liu, Hang-Yu Li
    Tumor Biology.2016; 37(10): 13951.     CrossRef
  • The cytomegalovirus protein UL138 induces apoptosis of gastric cancer cells by binding to heat shock protein 70
    Wenjing Chen, Kezhi Lin, Liang Zhang, Gangqiang Guo, Xiangwei Sun, Jing Chen, Lulu Ye, Sisi Ye, Chenchen Mao, Jianfeng Xu, Lifang Zhang, Lubin Jiang, Xian Shen, Xiangyang Xue
    Oncotarget.2016; 7(5): 5630.     CrossRef
  • Targeting the hsp70 gene delays mammary tumor initiation and inhibits tumor cell metastasis
    J Gong, D Weng, T Eguchi, A Murshid, M Y Sherman, B Song, S K Calderwood
    Oncogene.2015; 34(43): 5460.     CrossRef
Heat Shock Protein 70 and p53 Protein Expression in Colorectal Adenomas and Carcinomas.
Tae Jung Jang, Jung Ran Kim, Kung Bae Lee
Korean J Pathol. 1997;31(3):201-210.
  • 1,546 View
  • 17 Download
AbstractAbstract PDF
Heat shock protein 70 (HSP70) is a chaperone that binds to mutant p53 and consequently can regulate its accumulation or localization. Its expression is upregulated in tumor cells. We studied 44 adenomas and 29 carcinomas of colorectum to evaluate the expression of HSP70, and to assess the correlation among p53 protein and other clinical prognostic parameters. HSP70 expression was scored according to staining intensity and extent. p53 protein expression was 45.5%(20/44) in adenomas and 79.3%(23/29) in carcinomas(P<0.01). p53 protein expression of carcinomas was 57.1%(4/7) in diploidy tumors, 100.0%(8/8) in aneuploidy tumors(P=0.07), 100.0%(8/8) in well-differentiated tumors, and 50.0%(2/4) in poorly differentiated tumors(P= 0.09). HSP70 expression mainly revealed a fine granular cytoplasmic staining pattern in tumor cells. HSP70 was focally detected in some lymphocyte, ganglion cell and normal mucosa. HSP70 expression was 46.3%(19/41) in adenomas and 93.1%(27/29) in carcinomas. HSP70 score was 0.9+/-1.3 in adenomas(n=41) and 5.5+/-3.5 in carcinomas(n=29)(P<0.0005). Its score was 1.7+/-1.6 in p53 positive adenomas and 0.3+/-0.6 in p53 negative adenomas(P<0.005), and its expression rate was higher in p53 positive carcinomas than p53 negative carcinomas (P>0.05). There was no significant correlation among HSP70, tumor size, Dukes'stage, nodal metastasis, depth of tumor invasion, DNA ploidy and tumor differentiation. In conclusion, HSP70 and p53 protein appear to be correlated to each other, and that HSP70 and p53 protein may play a certain role in the progression of colorectal tumor. Further studies are needed for determining their prognostic factors in colorectal carcinoma.
Role of HSP70 Expression in the Development of Endometrial Adenocarcinoma Correlation of ER, PR, p53, and bcl-2 protein expressions and apoptosis .
Mi Seon Kang, Seo Young Park, Sang Bo Lee, Hye Kyoung Yoon
Korean J Pathol. 2000;34(5):358-365.
  • 1,429 View
  • 12 Download
AbstractAbstract PDF
Heat shock protein of 72 kDa (HSP70) has a role in the functional modulation of sex steroid hormone receptors and in p53-associated oncogenesis and inhibits apoptosis associated with bcl-2. However, the exact role of HSP70 in the development of endometrial adenocarcinoma has not been well established. The aim of this study is to evaluate the role of HSP70 in relation with ER, PR, p53 and bcl-2 expressions and apoptosis in benign and malignant endometrial lesions. Immunohistochemical studies for HSP70, ER, PR, p53, bcl-2 and TUNEL method for apoptosis were performed in 30 cases of adenocarcinoma and 30 cases of benign endometrial lesions consisted of each 10 cases of disordered proliferative endometrium (DP), simple or complex hyperplasia (HP), and atypical hyperplasia (AH). There were no significant differences of HSP70 and bcl-2 expression rates and apoptotic index (AI) between DP, HP, AH, and adenocarcinoma. p53 expression rate in adenocarcinoma was 36.7%, but no p53 expression was identified in DP, HP and AH (p<0.05). In adenocarcinoma, HSP70 expression rate was higher in ER and PR negative adenocarcinoma (p<0.05), and p53 expression rate was higher in nonendometrioid type and FIGO grade II and III (p<0.05), but no significant difference of bcl-2 expression rate according to the histological type and FIGO grade. AI was higher in nonendometrioid type (p<0.05). There was no correlation between HSP70, p53 and bcl-2 expressions, and no significant difference of AI according to HSP70, ER, PR, p53, and bcl-2 expressions. In conclusion, higher HSP70 expression rate in poorly differentiated and ER and PR negative adenocarcinoma suggests that HSP70 inhibits ER and PR expression and may be involved in the development of poorly differentiated endometrial adenocarcinoma.

J Pathol Transl Med : Journal of Pathology and Translational Medicine