Journal of Pathology and Translational Medicine

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

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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

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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; 55(2): 599. 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

p53, Heat Shock Protein 70 and Topoisomerase II Expression in Gallbladder Carcinoma.: Dae Cheol Kim, Mee Sook Roh, Jin Sook Jeong; Korean J Pathol. 2006;40(6):432-438.

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Abstract PDF: BACKGROUND
The present study was designed to investigate the expression of p53, Heat Shock Protein 70 (HSP70), and Topoisomerase (Topo) II alpha in the preneoplastic lesions and carcinomas of the gallbladder (GB) and to assess the correlation between the expression of these proteins and the clinicopathologic parameters by performing immunohistochemistry.
METHODS
The immunohistochemical expressions of p53, HSP70 and Topo II alpha were evaluated in 38 gallbladder carcinomas and 3 adenomas. Fifteen CIS(s) and 8 dysplasias that were located adjacent to invasive carcinomas were also studied.
RESULTS
A p53 expression was identified in 22 (57.9%) of the 38 GB carcinomas, in 9 (64.3%) of 14 CISs, and in none of the 8 dysplasias and 3 adenomas. A HSP70 expression was found in 11 (29%) of the 38 carcinomas, in 11 (78.6%) of 14 CIS(s), and in 4 (57.2%) of 7 dysplasias. A Topo II alpha expression was present in 36 (94.7%) of the 38 carcinomas, in 13 (92.9%) of 14 CIS(s), in 7 (100%) of 7 dysplasias and in 3 (100%) of 3 adenomas. p53 overexpression was related to the T stage of the primary tumor, while HSP70 and Topo II alpha were not related to any of the clinicopathologic parameters.
CONCLUSION
p53 may be involved in GB carcinogenesis and in the progression of cancer. p53 may be also helpful for making the differential diagnosis between dysplasia and CIS. A further large study is needed to better elucidate the roles of HSP70 and Topo II alpha in GB carcinogenesis.

Expression of Heat Shock Protein 27 and Apoptosis in Renal Cell Carcinomas.: Ghil Suk Yoon; Korean J Pathol. 2006;40(1):39-45.

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Abstract PDF: BACKGROUND
Heat shock protein 27 (HSP27) is induced by heat shock and other pathophysiologic stresses, including neoplastic transformation. We examined the relationship between the HSP27 expression and the clinical and histologic parameters to elucidate the biologic and prognostic significance of HSP27 in renal cell carcinomas (RCCs). Its regulation of apoptosis in RCC development was also observed.
METHODS
We performed immunohistochemical studies for HSP27, caspase 3 and TUNEL on paraffin-embedded tissue microarray specimens from 48 RCCs.
RESULTS
There was a tendency to higher expression of HSP27 in the RCC than in normal renal tubular cells. Of the 48 RCCs, the HSP27 expression was positive in 38 cases. An inverse relationship was found between the Fuhrman nuclear grade and HSP27 expression, but this was without statistical significance (r=-0.218, p=0.093). No relationship between the HSP27 expression and the other parameters was observed. Also, no statistically significant difference was observed between apoptosis and the HSP27 expression more (p=0.951).
CONCLUSIONS
Although HSP27 expression was increased in RCC than in normal renal tubular cell the HSP27 expression may not be a powerful and statistically significant prognostic indicator in patients with RCC.

Immunohistochemical Study of Heat Shock Protein(HSP) and Estrogen Receptor(ER) in the Normal Endometrium and in Adenocarcinoma of the Endometrium.: Hyuni Cho, Aeree Kim, Yung Suk Lee, Han Kyeom Kim, Insun Kim; Korean J Pathol. 1995;29(2):205-211.

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Abstract PDF: Heat shock protein(HSP), first found in the MCF-7 human breast tumor cell line is one of the estrogen-regulated proteins and its synthesis is stimulated by estradiol. In this study, immunohistochemical staining was done for estrogen receptor(ER) and HSP on formalin-fixed, paraffin-embedded tissue sections in twelve normal cyclic and twenty carcinomatous endometria. 1) During the proliferative and early secretary phases, the nuclei of surface and glandular epithelial cells and stromal cells had moderate to strong staining for ER, whereas during the mid and late secretary phases, the glandular epithelial and stromal cells had weak staining for ER. The surface epithelial cells had positive staining of variable intensity. 2) From the early proliferative to mid secretary phases, the glandular and surface epithelial cells showed a positive reaction of variable intensity for HSP. In the late secretary phase, the glandular and surface epithelial cells showed a weak positive or a negative reaction for HSP. During the menstrual cycle, the stromal cells remained negative for HSP. 3) In adenocarcinomas of the endometrium, 8 of 11 (72.7%) well differentiated carcinomas were positive for both ER and HSP, while only 3 of 9(33.3%) moderately and poorly differentiated carcinomas were positive for ER and HSP. In conclusion, ER and estrogen-regulated heat shock protein(HSP) were closely related in normal and carcinomatous endometria and the reactivity was decreased according to poor differentiation.

Amniotic Fluid Embolism of Lung: Clinical and histopathological study.: Tae Jung Kwon; Korean J Pathol. 1994;28(6):651-656.

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Abstract PDF: Amniotic fluid embolism is caused by the infusion of amniotic fluid into the maternal circulation with embolization to the lungs during pregnancy, labor or just after delivery. Clinically, this condition combines acute cardiopulmonary failure with a hemorrhagic tendency. We have experienced 11 autopsy cases of amniotic fluid embolism for about 2 years. The most common presenting feature was the postpartum uterine bleeding, followed by shock during oxytocin-induced labor. Histologically, various amount of amniotic debris, among which the most common component was epithelial squames, was demonstrated within the pulmonary vasculatures. In 4 cases, many fibrin thrombi were noted, reflecting the coagulation defect. Masson's trichrome and Alcian blue stains were proven to be valuable to demonstrate the squames and mucin, respectively.

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