Abstract
Introduction
The objective of this study was to determine the expression levels of metallothionein (MT) and p53 protein, recognized neoplastic transformation markers, in pancreatic serous cystadenomas (SCA) and adenomocarcinomas.
Materials and Methods
Neoplastic pancreatic tissue was taken from 20 patients with diagnosed benign (SCA: 5 cases) or malignant tumors (adenomocarcinomas: 15 cases) and control pancreatic tissue from healthy persons who had died in car accidents. Sections were stained with hematoxylin-eosin. Immunohistochemical localization of MT and p53 protein was carried out by LSAB2-HRP using specific antibodies against MT and p53.
Results
Metallothionein expression was observed only in the epithelial cells of the neoplastic tissue of SCAs. MT expression in the cystadenomas was weaker than in the healthy pancreatic tissue. No tissue was found with p53 protein expression. In the adenomocarcinomas, positive staining for MT was observed in 67% and p53 was positive in the carcinoma cells.
Conclusion
The weak MT expression and lack of p53 protein expression in pancreatic SCAs confirms the lack of local invasive potential of the neoplastic lesion. Increased expressions of MT and p53 were observed in the less differentiated tumors. Thus the expression of MT may be a potential prognostic marker for tumors.
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Abbreviations
- MT:
-
metallothionein
- SCA:
-
serous cystadenomas
- PAS:
-
periodic acid-Schiff
References
Abdel-Mageed AB, Agrawal KC (1998) Activation of nuclear factor kappaB: potential role in metallothionein-mediated mitogenic response. Cancer Res 58: 2335–2338
Alrefaie W, Katz MH, Easter DW et al (2004) Simultaneous serous cystadenoma of the pancreas and mucinous cystadenoma of the appendix. J Pancreas 5: 97–100
Bartsch D, Bastian D, Barth P et al (1998) K-ras oncogene mutations indicate malignancy in cystic tumors of the pancreas. Ann Surg 228: 79–86
Cherian MG (1994) The significance of the nuclear and cytoplasmic tumor of metallothionein in human liver and tumor cells. Environ Health Perspect 102(suppl 3): 131–135
Cherian MG, Apostolova MD (2000) Nuclear localization of metallothionein during cell proliferation and differentiation.. Cell Mol Biol 46: 347–356
Compton CC (2000) Serous cystic tumors of the pancreas.. Semin Diagn Pathol 17: 43–55
Coyle P, Philcox JC, Carey LC et al (2002) Metallothionein: the multipurpose protein. Cell Mol Life Sci 59: 627–647
Danielson KG, Ohi S, Huang PC (1982) Immunochemical detection of metallothionein in specific epithelial cells of rat organs. Proc Natl Asad Sci USA 79: 2301–2304
Davis SR, Cousins RJ (2000) Metallothionein expression in animals: A physiological perspective on function. J Nutr 130: 1085–1088
del Vecchio MT, Pergola L, Tripodi SA et al (2002) Microcystic adenoma associated with a mucinous cystadenocarcinoma: a “collision tumor” of the pancreas. Pancreas 24: 106–108
Fan LZ, Cherian MG (2002) Potential role of p53 on metallothionein induction in human epithelial breast cancer cells. Br J Cancer 87: 1019–1026
Gerdes B, Wild A, Wittenberg J et al (2003) Tumor-suppressing pathways in cystic pancreatic tumors. Pancreas 26: 42–48
Hadama T., Kinoshita M., Kobayashi D et al (2002) Endogenous tumor necrosis factor promotes resistance to cellular stresses by inducing the metallothionein-1A gene. Anticancer Res 22: 4059–4063
Hainaut P, Milner J (1993) A structural role for metal ions in the “wide-type” conformation of the tumour suppressor protein p53. Cancer Res 53: 1739–1742
Ioachim EE, Goussia AC, Agnantis NJ et al (1999) Prognostic evaluation of metallothionein expression in human colorectal neoplasms. J Clin Pathol 52: 876–879
Ishikawa T, Nakao A, Nomoto S et al (1998) Immunohistochemical and molecular biological studies of serous cystadenoma of the pancreas. Pancreas 16: 40–44
Janssen AM, van Duijn W, Kubben FJ et al (2002) Prognostic significance of metallothionein in human gastrointestinal cancer.. Clin Cancer Res 8: 1889–1896
Joseph MG, Banerjee D, Kocha W et al (2001) Metallothionein expression in patients with small cell carcinoma of the lung. Correlation with other molecular markers and clinical outcome. Cancer 92: 836–842
Kagi JH (1991) Overview of metallothionein. Methods Enzymol 205: 613–626
Klassen CD, Liu J, Choudhuri S (1999) Metallothionein: an intracellular protein to protect against cadmium toxicity. Annu Rev Pharmacol Toxicol 39: 267–294
Klöppel G, Solcia E, Longnecker DS et al (1996) Histological typing of tumours of the exocrine pancreas, second edition.. Springer-Verlag, Berlin-Heidelberg-New York, pp 7–18
Kondo Y, Rusnak JM, Hoyt DG et al (1997) Enhanced apoptosis in metallothionein null cells. Mol Pharmacol 52: 195–201
Madej JA, Milnerowicz H, Dzimira S (1999) Immunohistochemical localization of metallothionein (MT) in epithelial tumors in animals. Med Wet 55: 806–808
Milnerowicz H, Sliwinska-Mosson M, Bizon A et al (2006) Expression of metallothionein and p53 in pancreatic tumors in relation to prognosis. Gut 55: A324
Montag AG, Fossati N, Michelassi F (1990) Pancreatic micro- cystic adenoma coexistent with pancreatic ductal carcinoma: a report of two cases. Am J Surg Pathol 14: 352–355
Nath R, Kambadur R, Gulati S et al (1988) Molecular aspects, physiological, functions, and clinical significance of metallothioneins.. Crit Rev Food Sci Nutr 27: 41–85
Nitta H, Hirota M, Ohkado A et al (2008) Coexistence of serous cystadenoma and ductal adenocarcinoma in the pancreas: a case report. Pancreas 36: 218–219
Ohshio G, Imamura T, Okada N et al (1996) Immunohistochemical study of metallothionein in pancreatic carcinomas.. J Cancer Res Clin Oncol 122: 351–355
Oyama T, Take H, Hikino T et al (1996) Immunohistochemical expression of metallothionein in invasive breast cancer in relation to proliferative activity, histology and prognosis. Oncology 53: 112–117
Pellegata NS, Sessa F, Renault B et al (1994) K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res 54: 1556–1560
Perez-Ordonez B, Nassem A, Lieberman PH et al (1996) Solid serous adenoma of the pancreas: the solid variant of serous cystadenoma. Am J Surg Pathol 20: 1401–1405
Pillai G, Roberts H, Gatter K et al (2003) p53 expression in normal paraffin-embedded tissue using different antibodies and antigen retrieval buffer systems. Histopathology 42: 83–87
Posniak HV, Olson MC, Demos TC (1991) Coexistent adenocarcinoma and microcystic adenoma of the pancreas. Clin Imaging 15: 220–222
Rabczynski J, Milnerowicz H, Sliwinska-Mosson M et al (2006) Hormone-producing serous cystadenoma of the pancreas. Neoplasma 53: 495–499
Saga Y, Hashimoto H, Yachiku S et al (2002) Immunohistochemical expression of metallothionein in human bladder cancer: correlation with histopathological parameters and patient survival. J Urol 168: 2227–2231
Santos LD, Chow C, Henderson CJ et al (2002) Serous oligocystic adenoma of the pancreas: a clinicopathological and immunohistochemical study of three cases with ultrastructural findings. Pathology 34: 148–156
Satoh K, Shimosegawa T, Moriizumi S et al (1996) K-ras mutation and p53 protein accumulation in intraductal mucin-hypersecreting neoplasms of the pancreas. Pancreas 12: 362–368
Schmid KW, Ellis IO, Gee JM et al (1993) Presence and possible significance of immunocytochemically demonstrable metallothionein over-expression in primary invasive ductal carcinoma of the breast. Virchows Arch A Pathol Anat Histopathol 422: 153–159
Schwartz D, Rotter V (1998) p53-dependent cell cycle control: response to genotoxic stress. Semin Cancer Biol 8: 325–336
Strobel O, Z’graggen K, Schmitz-Winnenthal FH et al (2003) Risk of malignancy in serous cystic neoplasms of the pancreas. Digestion 68: 24–33
Symonds H, Krall L, Remington L et al (1994) p53-dependent apoptosis suppresses tumor-growth and progression in-vivo. Cell 78: 703–711
Tekada A, Hisada H, Okada S et al (1997) Tumor cell growth is inhibited by suppressing metallothionein-I synthesis. Cancer Lett 116: 145–149
Tomita T (2000a) Metallothionein in pancreatic endocrine neoplasms. Mod Pathol 13: 389–395
Tomita T (2000b) New markers for pancreatic islets and islet cell tumors. Pathol Int 52: 425–432
Zelger B, Hittmair A, Schir M et al (1993) Immunohistochemically demonstrated metallothionein expression in malignant melanoma. Histopathology 23: 257–263
Zeng J, Heuchel R, Schaffner W et al (1991) Thionein (apometallothionein) can modulate DNA binding and transcription activation by zinc finger containing factor Sp1. FEBS Lett 279: 310–312
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Śliwińska-Mossoń, M., Milnerowicz, H., Rabczyński, J. et al. Immunohistochemical localization of metallothionein and p53 protein in pancreatic serous cystadenomas. Arch. Immunol. Ther. Exp. 57, 295–301 (2009). https://doi.org/10.1007/s00005-009-0033-x
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DOI: https://doi.org/10.1007/s00005-009-0033-x