Prognostic Significance of Heat Shock Protein 70 Expression in Early Gastric Carcinoma
4
조회
0
다운로드
1
인용
0
참고문헌
초록
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.
Abstract
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.
참고문헌 (30)
- Rüschoff J, "HER2 testing in gastric cancer : a practical approach", Mod Pathol, 25, pp.637~650 (2012)
- "Goyang: National Cancer Information Center"[URL]
- Jang BG, "Molecular pathology of gastric carcinoma", Pathobiology, 78, pp.302~310 (2011)
- Garrido C, "Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties", Cell Cycle, 5, pp.2592~2601 (2006)
- Nylandsted J, "Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2", Proc Natl Acad Sci U S A, 97, pp.7871~7876 (2000)
- Kaur J, "Cell surface expression of 70 kDa heat shock protein in human oral dysplasia and squamous cell carcinoma: correlation with clinicopathological features", Oral Oncol, 34, pp.93~98 (1998)
- Lazaris AC, "Heat shock protein 70 and HLA-DR molecules tissue expression: prognostic implications in colorectal cancer", Dis Colon Rectum, 38, pp.739~745 (1995)
- Ciocca DR, "Colocalization of estrogen and progesterone receptors with an estrogen-regulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue", Breast Cancer Res Treat, 16, pp.243~251 (1990)
- Elpek GO, "Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovaries", APMIS, 111, pp.523~530 (2003)
- Nanbu K, "Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas: correlation with clinicopathology, sex steroid receptor status, and p53 protein expression", Cancer, 77, pp.330~338 (1996)
- Ciocca DR, "Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications", Cell Stress Chaperones, 10, pp.86~103 (2005)
- Ciocca DR, "Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications", J Natl Cancer Inst, 85, pp.570~574 (1993)
- Chuma M, "Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma", Hepatology, 37, pp.198~207 (2003)
- Maehara Y, "Overexpression of the heat shock protein HSP70 family and p53 protein and prognosis for patients with gastric cancer", Oncology, 58, pp.144~151 (2000)
- Canoz O, "General features of gastric carcinomas and comparison of HSP70 and NK cell immunoreactivity with prognostic factors", Pathol Oncol Res, 8, pp.262~269 (2002)
- Isomoto H, "Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer", Cancer Lett, 198, pp.219~228 (2003)
- Edge SB, "AJCC cancer staging handbook: from the AJCC cancer staging manual" (2010), Springer
- Bosman FT, "WHO classification of tumours of the digestive system" (2010), IARC Press
- Piura B, "Heat shock proteins and malignancies of the female genital tract", Harefuah, 141, pp.969~972 (2002)
- Ciupitu AM, "Immunization with heat shock protein 70 from methylcholanthrene-induced sarcomas induces tumor protection correlating with in vitro T cell responses", Cancer Immunol Immunother, 51, pp.163~170 (2002)
- Zhao ZG, "Heat shock protein 70 antisense oligonucleotide inhibits cell growth and induces apoptosis in human gastric cancer cell line SGC-7901", World J Gastroenterol, 11, pp.73~78 (2005)
- Park CS, "An immunohistochemical analysis of heat shock protein 70, p53, and estrogen receptor status in carcinoma of the uterine cervix", Gynecol Oncol, 74, pp.53~60 (1999)
- Cornford PA, "Heat shock protein expression independently predicts clinical outcome in prostate cancer", Cancer Res, 60, pp.7099~7105 (2000)
- Fourie AM, "HSP70 binding sites in the tumor suppressor protein p53", J Biol Chem, 272, pp.19471~19479 (1997)
- Rohde M, "Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms", Genes Dev, 19, pp.570~582 (2005)
- Ramires M, "Ki67 labelling index in gastric carcinomas. An immunohistochemical study using double staining for the evaluation of the proliferative activity of diffuse-type carcinomas", J Pathol, 182, pp.62~67 (1997)
- Lim MS, "Predictable factors for lymph node metastasis in early gastric cancer-analysis of single institutional experience", J Gastrointest Surg, 15, pp.1783~1788 (2011)
- Shakoori AR, "Expression of heat shock genes during differentiation of mammalian osteoblasts and promyelocytic leukemia cells", J Cell Biochem, 48, pp.277~287 (1992)
- Spector NL, "Heat shock protein is a unique marker of growth arrest during macrophage differentiation of HL-60 cells", J Cell Physiol, 156, pp.619~625 (1993)
- Spector NL, "Regulation of the 28 kDa heat shock protein by retinoic acid during differentiation of human leukemic HL-60 cells", FEBS Lett, 337, pp.184~188 (1994)