Clinical significance of P‑glycoprotein and glutathione S‑transferase π expression in gallbladder carcinoma

Ma,Qing‑Jiu; Zhang,Yu‑Cun; Shi,Jing‑Sen; Li,Guo‑Cai

doi:10.3892/etm.2014.1472

Clinical significance of P‑glycoprotein and glutathione S‑transferase π expression in gallbladder carcinoma

Authors:
- Qing‑Jiu Ma
- Yu‑Cun Zhang
- Jing‑Sen Shi
- Guo‑Cai Li
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Affiliations: General Surgery Department, GaoXin Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi 710075, P.R. China, Hepatobiliary Department, First Hospital of Xi'an Jiao Tong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: January 2, 2014 https://doi.org/10.3892/etm.2014.1472
Pages: 635-639

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Abstract

P‑glycoprotein (P‑gp) and glutathione S‑transferase π (GST‑π) are not only drug‑resistance markers, but also prognostic markers of various cancers. The aim of the present study was to investigate the clinical significance of P‑gp and GST‑π in gallbladder carcinoma (GBC). Tissue samples from 42 patients with GBC were immunostained. Demographic, clinical and follow‑up data were collected and analyzed. The positive expression rates of P‑gp and GST‑π in the GBC tissues were significantly higher (76.2 and 64.3%, respectively) than that of chronic cholecystitis specimens (30 and 20%, respectively) (P=0.014 and 0.035, respectively), and correlated with the Nevin stage of GBC. Multivariate analysis demonstrated that patients with positive expression of P‑gp and GST‑π showed a significantly lower 2‑year survival rate (11.1 and 12%, respectively) compared with patients with negative expression (55.6 and 45.5%, respectively) (P=0.013 and 0.036, respectively). P‑gp was also found to be an independent prognostic marker of 2‑year survival rate by logistic regression analysis (B=‑2.76, P=0.061). Results of this study suggest that P‑gp is a prognostic marker of GBC and the detection of P‑gp and GST‑π may contribute to the prognosis of GBC and the application of chemotherapy as a therapeutic treatment.

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1	Mekeel KL and Hemming AW: Surgical management of gallbladder carcinoma: a review. J Gastrointest Surg. 11:1188–1193. 2007. View Article : Google Scholar : PubMed/NCBI
2	Miller G and Jarnagin WR: Gallbladder carcinoma. Eur J Surg Oncol. 34:306–312. 2008. View Article : Google Scholar
3	Khdair A, Handa H, Mao G and Panyam J: Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro. Eur J Pharm Biopharm. 71:214–222. 2008. View Article : Google Scholar : PubMed/NCBI
4	Schrader AJ, Seger M, Konrad L, et al: Clinical impact of MDR1-expression in testicular germ cell cancer. Exp Oncol. 29:212–216. 2007.PubMed/NCBI
5	Bark H, Xu HD, Kim SH, Yun J and Choi CH: P-glycoprotein down-regulates expression of breast cancer resistance protein in a drug-free state. FEBS Lett. 582:2595–2600. 2008. View Article : Google Scholar : PubMed/NCBI
6	Berger W, Setinek U, Hollaus P, et al: Multidrug resistance markers P-glycoprotein, multidrug resistance protein 1, and lung resistance protein in non-small cell lung cancer: prognostic implications. J Cancer Res Clin Oncol. 131:355–363. 2005. View Article : Google Scholar
7	Bottke D, Koychev D, Busse A, et al: Fractionated irradiation can induce functionally relevant multidrug resistance gene and protein expression in human tumor cell lines. Radiat Res. 170:41–48. 2008. View Article : Google Scholar
8	Hanson JA, Gillespie JW, Grover A, et al: Gene promoter methylation in prostate tumor-associated stromal cells. J Natl Cancer Inst. 98:255–261. 2006. View Article : Google Scholar : PubMed/NCBI
9	Pandey SN, Jain M, Nigam P, Choudhuri G and Mittal B: Genetic polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3 and the susceptibility to gallbladder cancer in North India. Biomarkers. 11:250–261. 2006. View Article : Google Scholar : PubMed/NCBI
10	Tiirikainen MI, Elonen E, Syrjälä MT, Jansson SE and Krusius T: Flow cytometric analysis of glutathione-S-transferase-pi in acute leukemia. Leukemia. 8:978–984. 1994.PubMed/NCBI
11	Somlo G, Chu P, Frankel P, et al: Molecular profiling including epidermal growth factor receptor and p21 expression in high-risk breast cancer patients as indicators of outcome. Ann Oncol. 19:1853–1859. 2008. View Article : Google Scholar : PubMed/NCBI
12	Perry AS, Loftus B, Moroose R, et al: In silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer. Br J Cancer. 96:1587–1594. 2007. View Article : Google Scholar : PubMed/NCBI
13	Sutoh I, Kohno H, Nakashima Y, et al: Concurrent expressions of metallothionein, glutathione S-transferase-pi, and P-glycoprotein in colorectal cancers. Dis Colon Rectum. 43:221–232. 2000. View Article : Google Scholar : PubMed/NCBI
14	Nevin JE, Moran TJ, Kay S and King R: Carcinoma of the gallbladder: staging, treatment, and prognosis. Cancer. 37:141–148. 1976. View Article : Google Scholar : PubMed/NCBI
15	Henson DE, Albores-Saavedra J and Corle D: Carcinoma of the gallbladder. Histologic types, stage of disease, grade, and survival rates. Cancer. 70:1493–1497. 1992. View Article : Google Scholar : PubMed/NCBI
16	Levy AD, Murakata LA and Rohrmann CA Jr: Gallbladder Carcinoma: radiologic-pathologic correlation. Radiographics. 21:295–314. 2001. View Article : Google Scholar : PubMed/NCBI
17	Gottesman MM and Pastan I: The multidrug transporter, a double-edged sword. J Biol Chem. 263:12163–12166. 1988.PubMed/NCBI
18	Rodriguez C, Commes T, Robert J and Rossi JF: Expression of P-glycoprotein and anionic glutathione S-transferase genes in non-Hodgkin’s lymphoma. Leuk Res. 17:149–154. 1993.PubMed/NCBI
19	Kufe DW, Pollock RE, Weichselbaum RR, et al: Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; pp. 711–726. 2003
20	Stewart DJ: Mechanisms of resistance to cisplatin and carboplatin. Crit Rev Oncol Hematol. 63:12–31. 2007. View Article : Google Scholar : PubMed/NCBI
21	Chen YK and Lin LM: Placental glutathione S-transferase isoenzyme expression in polycyclic aromatic hydrocarbon-induced hemster buccal pouch mucosa. Oral Oncol. 34:180–185. 1998. View Article : Google Scholar
22	Tsuchida S and Sato K: Glutathione transferses and cancer. Crit Rev Biochem Mol Biol. 27:337–384. 1992. View Article : Google Scholar : PubMed/NCBI
23	Takabayashi A, Watkins JB, Soloway RD, Rios-Dalenz J and Henson DE: Glycolithocolic acid is greatly increased in stones from patients with carcinoma of the gallbladder. Gastroenterology. 79:1058–1063. 1980.
24	Henson DE, Albores-Saavedra J and Corle D: Carcinoma of the gallbladder. Histologic types, stage of disease, grade, and survival rates. Cancer. 70:1493–1497. 1992. View Article : Google Scholar : PubMed/NCBI
25	Lazcano-Ponce EC, Miquel JF, Muñoz N, et al: Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin. 51:349–364. 2001. View Article : Google Scholar : PubMed/NCBI
26	Seo S, Hatano E, Higashi T, et al: Fluorine-18 fluorodeoxyglucose positron emission tomography predicts tumor differentiation, P-glycoprotein expression, and outcome after resection in hepatocellular carcinoma. Clin Cancer Res. 13:427–433. 2007. View Article : Google Scholar
27	Sinicrope FA, Hart J, Brasitus TA, Michelassi F, Lee JJ and Safa AR: Relationship of P-glycoprotein and carcinoenbryonic antigen expression in human colon carcinoma to local invision, DNA ploidy, and disease relapse. Cancer. 74:2908–2907. 1994. View Article : Google Scholar : PubMed/NCBI
28	Saint-Ruf C, Malfoy B, Scholl S, Zafrani B and Dutrillaux B: GST gene is frequently complified with INT2 and HSTF1 proto-oncogene in human breast cancers. Oncogene. 16:403–406. 1991.PubMed/NCBI
29	Slebos RJ, Kibbelaar RE, Dalesio O, et al: K-ras oncogene activation as a prognostic marker in adenocarcinomar of the lung. N Eng J Med. 323:561–565. 1990. View Article : Google Scholar : PubMed/NCBI
30	Tsuda H, Hirohashi S, Shimosato Y, et al: Correlation between long-term survival in breast cancer patients and amplification of two putive oncogene-coamplification units: hst-1/int-2 and c-erbB-2/ear-1. Cancer Res. 49:3104–3108. 1989.PubMed/NCBI
31	Charpin C, Vielh P, Duffaud F, et al: Quantitative immunocytochemical assays of P-glycoprotein in breast carcinoma: correlation to messanger RNA experession and to immunohistochemical prognostic indicators. J Natl Cancer Inst. 86:1539–1545. 1994. View Article : Google Scholar
32	Ralhan R, Swain RK, Agarwal S, et al: P-glycoprotein is positively correlated with p53 in human oral pre-malignant and malignant lesions and is associated with poor prognosis. Int J Cancer. 84:80–85. 1999. View Article : Google Scholar : PubMed/NCBI
33	Malik IA: Gallbladder cancer: current status. Expert Opin Pharmacother. 5:1271–1277. 2004. View Article : Google Scholar : PubMed/NCBI
34	Brotherick I, Shenton BK, Egan M, et al: Examination of multidrug resistance in cell lines and primary breast tumours by flow cytometry. Eur J Cancer. 32A:2334–2341. 1996. View Article : Google Scholar : PubMed/NCBI