[해외논문]
Metallothionein expression in ovarian cancer in relation to histopathological parameters and molecular markers of prognosis
원문보기
International journal of cancer: Journal international du cancer ,
v.95 no.2 ,
2001년, pp.121 - 127
Hengstler, J.G.
(Institute of Toxicology, University of Mainz, Mainz, Germany)
,
Pilch, H.
(Department of Gynecology, University of Mainz, Mainz, Germany)
,
Schmidt, M.
(Department of Gynecology, University of Mainz, Mainz, Germany)
,
Dahlenburg, H.
(Department of Gynecology, University of Mainz, Mainz, Germany)
,
Sagemüller, J.
(Department of Gynecology, University of Mainz, Mainz, Germany)
,
Schiffer, I.
(Department of Gynecology, University of Mainz, Mainz, Germany)
,
Oesch, F.
(Department of Gynecology, University of Mainz, Mainz, Germany)
,
Knapstein, P.G.
(Department of Gynecology, University of Mainz, Mainz, Germany)
,
Kaina, B.
(Department of Gynecology, University of Mainz, Mainz, Germany)
,
Tanner, B.
(Department of Gynecology, University of Mainz, Mainz, Germany)
Metallothioneins (MTs) and glutathione constitute the major fractions of intracellular thiol factors. Abundant nucleophilic sulfhydryl groups can interact with many electrophilic substances, including several anti-neoplastic agents, participate in controlling intracellular redox potential, and act a...
Metallothioneins (MTs) and glutathione constitute the major fractions of intracellular thiol factors. Abundant nucleophilic sulfhydryl groups can interact with many electrophilic substances, including several anti-neoplastic agents, participate in controlling intracellular redox potential, and act as scavengers of reactive oxygen species. In the present study, we examined the relation of MTs (alone and in combination with glutathione) to histopathological parameters and survival time of ovarian cancer patients. Expression of the major MT isoforms (MT-1 and MT-2) was determined by immunohistochemistry on paraffin-embedded tumor specimens from 189 patients, 151 suffering from primary epithelial ovarian cancer and 38 from recurrences. MT was negatively associated with survival time when all patients with primary carcinomas (n = 151) were analyzed (p = 0.049, log-rank test). However, no significant association between MT expression and survival was obtained when subgroups of patients with histological grade 1, 2 or 3 carcinomas were analyzed. Similarly, no significant association of MT expression and survival was obtained with the proportional hazards model adjusted for histological grade. This scenario can be explained by a correlation between MT expression and histological grade: MT was detectable in 26%, 48% and 62% of grade 1, 2 and 3 carcinomas, respectively (p = 0.008, χ2 test). An interesting hypothesis is generated by combined analysis of MT and total glutathione content (GSH). The product of MT and GSH levels (MT × GSH) was negatively associated with survival of grade 1 carcinomas (p = 0.021, log-rank test) but not with grade 2 and 3 carcinomas (p = 0.176 and 0.403, respectively). When MT × GSH was greater than the median, 25% of patients with grade 1 carcinomas died within 235 days. In contrast, all patients with grade 1 carcinomas survived when MT × GSH in tumor tissue was smaller than the median. This suggests that high expression of sulfhydryl factors might facilitate survival and progression of low-grade ovarian cancer cells. A significant correlation was obtained between MT expression and mutant p53 (p = 0.037, χ2 test). However, this might be an indirect effect since both MT (p = 0.008) and mutant p53 (p = 0.000) were associated with histological grade. In conclusion, MT expression as well as the product of MT and GSH were associated with histological grade of primary ovarian carcinomas. High expression of both sulfhydryl factors may identify a subgroup of low-grade carcinomas with an increased risk of progression. © 2001 Wiley-Liss, Inc.
Metallothioneins (MTs) and glutathione constitute the major fractions of intracellular thiol factors. Abundant nucleophilic sulfhydryl groups can interact with many electrophilic substances, including several anti-neoplastic agents, participate in controlling intracellular redox potential, and act as scavengers of reactive oxygen species. In the present study, we examined the relation of MTs (alone and in combination with glutathione) to histopathological parameters and survival time of ovarian cancer patients. Expression of the major MT isoforms (MT-1 and MT-2) was determined by immunohistochemistry on paraffin-embedded tumor specimens from 189 patients, 151 suffering from primary epithelial ovarian cancer and 38 from recurrences. MT was negatively associated with survival time when all patients with primary carcinomas (n = 151) were analyzed (p = 0.049, log-rank test). However, no significant association between MT expression and survival was obtained when subgroups of patients with histological grade 1, 2 or 3 carcinomas were analyzed. Similarly, no significant association of MT expression and survival was obtained with the proportional hazards model adjusted for histological grade. This scenario can be explained by a correlation between MT expression and histological grade: MT was detectable in 26%, 48% and 62% of grade 1, 2 and 3 carcinomas, respectively (p = 0.008, χ2 test). An interesting hypothesis is generated by combined analysis of MT and total glutathione content (GSH). The product of MT and GSH levels (MT × GSH) was negatively associated with survival of grade 1 carcinomas (p = 0.021, log-rank test) but not with grade 2 and 3 carcinomas (p = 0.176 and 0.403, respectively). When MT × GSH was greater than the median, 25% of patients with grade 1 carcinomas died within 235 days. In contrast, all patients with grade 1 carcinomas survived when MT × GSH in tumor tissue was smaller than the median. This suggests that high expression of sulfhydryl factors might facilitate survival and progression of low-grade ovarian cancer cells. A significant correlation was obtained between MT expression and mutant p53 (p = 0.037, χ2 test). However, this might be an indirect effect since both MT (p = 0.008) and mutant p53 (p = 0.000) were associated with histological grade. In conclusion, MT expression as well as the product of MT and GSH were associated with histological grade of primary ovarian carcinomas. High expression of both sulfhydryl factors may identify a subgroup of low-grade carcinomas with an increased risk of progression. © 2001 Wiley-Liss, Inc.
Keyword
참고문헌 (32)
Drug Metab Rev Moffatt 29 261 1997 10.3109/03602539709037585
Gen Pharmacol Ebadi 25 1297 1994 10.1016/0306-3623(94)90152-X
Proc Natl Acad Sci USA Palmiter 89 6333 1992 10.1073/pnas.89.14.6333
J Biol Chem Nielson 259 4941 1984 10.1016/S0021-9258(17)42937-1
J Am Chem Soc Margoshes 79 4813 1957 10.1021/ja01574a064
Toxicol Appl Pharmacol Liu 149 24 1998 10.1006/taap.1997.8325
Mol Pharmacol Kondo 52 195 1997 10.1124/mol.52.2.195
Proc Natl Acad Sci USA Masters 584 1994 10.1073/pnas.91.2.584
Proc Natl Acad Sci USA Michalska 90 8088 1993 10.1073/pnas.90.17.8088
Science Kelley 241 1813 1988 10.1126/science.3175622
Cancer Res Basu 51 893 1991
Cancer Res Kasahara 51 3237 1991
Carcinogenesis Lohrer 11 1937 1990 10.1093/carcin/11.11.1937
Mutat Res Robson 274 177 1992 10.1016/0921-8777(92)90064-A
Int J Cancer Schilder 45 416 1990 10.1002/ijc.2910450306
J Urol Bahnson 146 1518 1991 10.1016/S0022-5347(17)38155-7
Mod Pathol Wood 6 33 1993
Br J Cancer Murphy 63 711 1991 10.1038/bjc.1991.160
Int J Gynecol Pathol Germain 15 54 1996 10.1097/00004347-199601000-00009
Int J Cancer Hengstler 84 388 1999 10.1002/(SICI)1097-0215(19990820)84:4<388::AID-IJC10>3.0.CO;2-3
Int J Cancer Tanner 74 438 1997 10.1002/(SICI)1097-0215(19970822)74:4<438::AID-IJC13>3.0.CO;2-5
Cancer Res Hengstler 59 3206 1999
Gynecol Oncol Tanner 65 54 1997 10.1006/gyno.1996.4593
Int J Gynecol Pathol Tanner 17 66 1998 10.1097/00004347-199801000-00012
Toxicol Appl Pharmacol Yamada-Okabe 133 233 1995 10.1006/taap.1995.1146
Blaustein?s pathology of the female genital tract Czernobilski 560 1987 10.1007/978-1-4757-1942-0_18 Blaustein?s pathology of the female genital tract. New York: Springer, 1987: 560-607.
Virchows Arch Douglas-Jones 430 373 1997 10.1007/s004280050046
Anal Biochem Griffith 106 207 1980 10.1016/0003-2697(80)90139-6
Mutat Res Oesch 321 175 1994 10.1016/0165-1218(94)90042-6
Anal Biochem Bradford 72 248 1976 10.1016/0003-2697(76)90527-3
The statistical analysis of failure data Kalbfleisch 1980 The statistical analysis of failure data. New York: Wiley, 1980.
Int J Gynecol Pathol Meden 17 61 1998 10.1097/00004347-199801000-00011
더보기
AI-Helper
※ AI-Helper는 부적절한 답변을 할 수 있습니다.