Skip to main content
Top
Published in: Virchows Archiv 5/2005

01-05-2005 | Original Article

Analysis of trefoil factor family protein 1 (TFF1, pS2) expression in chronic cholecystitis and gallbladder carcinoma

Authors: Peter Kornprat, Peter Rehak, Martina Lemmerer, Margit Gogg-Kamerer, Cord Langner

Published in: Virchows Archiv | Issue 5/2005

Login to get access

Abstract

Trefoil factor family protein 1 (TFF1, pS2) interacts with mucins to protect gastrointestinal epithelium against injury and contributes to mucosal repair by promoting epithelial cell migration and restitution. Moreover, TFF1 has antiproliferative and anti-apoptotic effects and promotes cell scattering and invasion. We investigated TFF1 expression in healthy and inflamed non-neoplastic gallbladder mucosa as well as in gallbladder carcinomas (n=57) and corresponding metastases (n=18), using a tissue microarray technique. TFF1 immunoreactivity was absent in healthy mucosa, focally observed in epithelium with inflammatory changes and present in 35% of primary and 24% of metastatic cancer tissues. Immunoreactivity significantly decreased with increasing tumour stage (P=0.009) and increasing tumour grade (P=0.001). Patients with TFF1 positive tumours showed a more favourable outcome compared to patients with TFF1 negative tumours in univariate analysis (P=0.006). However, multivariate analysis proved resection status and tumour grade as the only independent prognostic factors. In conclusion, TFF1 is expressed in inflamed non-neoplastic gallbladder epithelium and in low stage and low grade gallbladder carcinomas. Thus, TFF1 may be the missing link between gallstones, chronic cholecystitis and gallbladder cancer. Further studies are needed to evaluate whether TFF1 immunostaining can be used as a diagnostic tool to identify patients with a more favourable outcome.
Literature
1.
go back to reference Albores-Saavedra J, Scoazec JC, Wittekind C, Sripa B, Menck HR, Soehendra N, Sriram PVJ (2000) Tumours of the gallbladder and extrahepatic bile ducts. In: Hamilton SR, Aaltonen LA (eds) WHO classification of tumours. Pathology and genetics. Tumours of the digestive system. IARC Press, Lyon, pp 203–218 Albores-Saavedra J, Scoazec JC, Wittekind C, Sripa B, Menck HR, Soehendra N, Sriram PVJ (2000) Tumours of the gallbladder and extrahepatic bile ducts. In: Hamilton SR, Aaltonen LA (eds) WHO classification of tumours. Pathology and genetics. Tumours of the digestive system. IARC Press, Lyon, pp 203–218
2.
go back to reference Balleine RL, Clarke CL (1999) Expression of the oestrogen responsive protein pS2 in human breast cancer. Histol Histopathol 14:571–578 Balleine RL, Clarke CL (1999) Expression of the oestrogen responsive protein pS2 in human breast cancer. Histol Histopathol 14:571–578
3.
go back to reference Bossenmeyer-Pourié C, Kannan R, Ribieras S, Wendling C, Stoll I, Thim L, Tomasetto C, Rio MC (2002) The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis. J Cell Biol 157:761–770 Bossenmeyer-Pourié C, Kannan R, Ribieras S, Wendling C, Stoll I, Thim L, Tomasetto C, Rio MC (2002) The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosis. J Cell Biol 157:761–770
4.
go back to reference Donohue JH, Stewart AK, Menck HR (1998) The national cancer data base report on carcinoma of the gallbladder, 1989–1995. Cancer 83:2618–2628 Donohue JH, Stewart AK, Menck HR (1998) The national cancer data base report on carcinoma of the gallbladder, 1989–1995. Cancer 83:2618–2628
5.
go back to reference Emami S, Le Floch N, Bruyneel E, Thim L, May F, Westley B, Rio MC, Mareel M, Gespach C (2001) Induction of scattering and cellular invasion by trefoil peptides in src- and RhoA-transformed kidney and colonic epithelial cells. FASEB J 15:351–361 Emami S, Le Floch N, Bruyneel E, Thim L, May F, Westley B, Rio MC, Mareel M, Gespach C (2001) Induction of scattering and cellular invasion by trefoil peptides in src- and RhoA-transformed kidney and colonic epithelial cells. FASEB J 15:351–361
6.
go back to reference Hackel C, Falkenberg B, Gunther T, Lippert H, Roessner A (1998) The pS2 protein in colorectal carcinomas and metastases. Pathol Res Pract 94:171–176 Hackel C, Falkenberg B, Gunther T, Lippert H, Roessner A (1998) The pS2 protein in colorectal carcinomas and metastases. Pathol Res Pract 94:171–176
7.
go back to reference Higashiyama M, Doi O, Kodama K, Yokouchi H, Inaji H, Nakamori S, Tateishi R (1994) Prognostic significance of pS2 protein expression in pulmonary adenocarcinoma. Eur J Cancer 30A:792–797 Higashiyama M, Doi O, Kodama K, Yokouchi H, Inaji H, Nakamori S, Tateishi R (1994) Prognostic significance of pS2 protein expression in pulmonary adenocarcinoma. Eur J Cancer 30A:792–797
8.
go back to reference Ito H, Matros E, Brooks DC, Osteen RT, Zinner MJ, Swanson RS, Ashley SW, Whang EE (2004) Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg 8:183–190 Ito H, Matros E, Brooks DC, Osteen RT, Zinner MJ, Swanson RS, Ashley SW, Whang EE (2004) Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg 8:183–190
9.
go back to reference Katoh M (2003) Trefoil factors and human gastric cancer. Int J Mol Med 12:3–9 Katoh M (2003) Trefoil factors and human gastric cancer. Int J Mol Med 12:3–9
10.
go back to reference Kirikoshi H, Katoh M (2002) Expression of TFF1, TFF2 and TFF3 in gastric cancer. Int J Oncol 21:655–659 Kirikoshi H, Katoh M (2002) Expression of TFF1, TFF2 and TFF3 in gastric cancer. Int J Oncol 21:655–659
11.
go back to reference Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847PubMed Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847PubMed
12.
go back to reference Koshiyama M, Yoshida M, Konishi M, Takemura M, Yura Y, Matsushita K, Hayashi M, Tauchi K (1997) Expression of pS2 protein in endometrial carcinomas: correlation with clinicopathologic features and sex steroid receptor status. Int J Cancer 74:237–244 Koshiyama M, Yoshida M, Konishi M, Takemura M, Yura Y, Matsushita K, Hayashi M, Tauchi K (1997) Expression of pS2 protein in endometrial carcinomas: correlation with clinicopathologic features and sex steroid receptor status. Int J Cancer 74:237–244
13.
go back to reference Lazcano-Ponce EC, Miquel JF, Munoz N, Herrero R, Ferrecio C, Wistuba II, Alonso de Ruiz P, Aristi Urista G, Nervi F (2001) Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin 51:349–364 Lazcano-Ponce EC, Miquel JF, Munoz N, Herrero R, Ferrecio C, Wistuba II, Alonso de Ruiz P, Aristi Urista G, Nervi F (2001) Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin 51:349–364
14.
go back to reference Lefebvre O, Chenard MP, Masson R, Linares J, Dierich A, LeMeur M, Wendling C, Tomasetto P, Chambon P, Rio MC (1996) Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein. Science 274:259–262 Lefebvre O, Chenard MP, Masson R, Linares J, Dierich A, LeMeur M, Wendling C, Tomasetto P, Chambon P, Rio MC (1996) Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein. Science 274:259–262
15.
go back to reference Leung WK, Yu J, Chan FK, To KF, Chan MW, Ebert MP, Ng EK, Chung SC, Malfertheiner P, Sung JJ (2002) Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas, intestinal metaplasia, and non-neoplastic gastric tissues. J Pathol 197:582–588 Leung WK, Yu J, Chan FK, To KF, Chan MW, Ebert MP, Ng EK, Chung SC, Malfertheiner P, Sung JJ (2002) Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas, intestinal metaplasia, and non-neoplastic gastric tissues. J Pathol 197:582–588
16.
go back to reference Li X, Hui AM, Shi YZ, Takayama T, Makuuchi M (2001) Reduced p21(WAF1/CIP1) expression is an early event in gallbladder carcinogenesis and is of prognostic significance for patients with carcinomas of the gallbladder. Hum Pathol 32:771–777 Li X, Hui AM, Shi YZ, Takayama T, Makuuchi M (2001) Reduced p21(WAF1/CIP1) expression is an early event in gallbladder carcinogenesis and is of prognostic significance for patients with carcinomas of the gallbladder. Hum Pathol 32:771–777
17.
go back to reference Lipponen PK, Eskelinen MJ (1994) Expression of pS2 protein transitional cell bladder tumours. J Pathol 173:327–332 Lipponen PK, Eskelinen MJ (1994) Expression of pS2 protein transitional cell bladder tumours. J Pathol 173:327–332
18.
go back to reference Longman RJ, Thomas MG, Poulsom R (1999) Trefoil peptides and surgical disease. Br J Surg 86:740–748 Longman RJ, Thomas MG, Poulsom R (1999) Trefoil peptides and surgical disease. Br J Surg 86:740–748
19.
go back to reference Machado JC, Carneiro F, Ribeiro P, Blin P, Sobrinho-Simoes M (1996) pS2 protein expression in gastric carcinoma. An immunohistochemical and immunoradiometric study. Eur J Cancer 32A:1585–1590 Machado JC, Carneiro F, Ribeiro P, Blin P, Sobrinho-Simoes M (1996) pS2 protein expression in gastric carcinoma. An immunohistochemical and immunoradiometric study. Eur J Cancer 32A:1585–1590
20.
go back to reference Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P (1982) Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast-cancer cell line. Nucleic Acids Res 10:7895–7903 Masiakowski P, Breathnach R, Bloch J, Gannon F, Krust A, Chambon P (1982) Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast-cancer cell line. Nucleic Acids Res 10:7895–7903
21.
go back to reference Müller W, Borchard F (1993) pS2 protein in gastric carcinoma and normal gastric mucosa: association with clinicopathological parameters and patient survival. J Pathol 171:263–269 Müller W, Borchard F (1993) pS2 protein in gastric carcinoma and normal gastric mucosa: association with clinicopathological parameters and patient survival. J Pathol 171:263–269
22.
go back to reference Nocito A, Bubendorf L, Tinner ME, Suess K, Wagner U, Forster T, Kononen J, Fijan A, Bruderer J, Schmid U, Ackermann D, Maurer R, Alund G, Knonagel H, Rist M, Anabitarte M, Hering F, Hardmeier T, Schoenenberger AJ, Flury R, Jager P, Fehr LJ, Schraml P, Moch H, Mihatsch MJ, Gasser T, Sauter G (2001) Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J Pathol 194:349–357CrossRefPubMed Nocito A, Bubendorf L, Tinner ME, Suess K, Wagner U, Forster T, Kononen J, Fijan A, Bruderer J, Schmid U, Ackermann D, Maurer R, Alund G, Knonagel H, Rist M, Anabitarte M, Hering F, Hardmeier T, Schoenenberger AJ, Flury R, Jager P, Fehr LJ, Schraml P, Moch H, Mihatsch MJ, Gasser T, Sauter G (2001) Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J Pathol 194:349–357CrossRefPubMed
23.
go back to reference North JH Jr, Pack MS, Hong C, Rivera DE (1998) Prognostic factors for adenocarcinoma of the gallbladder: an analysis of 162 cases. Am Surg 64:437–440 North JH Jr, Pack MS, Hong C, Rivera DE (1998) Prognostic factors for adenocarcinoma of the gallbladder: an analysis of 162 cases. Am Surg 64:437–440
24.
go back to reference Parwani AV, Geradts J, Caspers E, Offerhaus GJ, Yeo CJ, Cameron JL, Klimstra DS, Maitra A, Hruban RH, Argani P (2003) Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions. Mod Pathol 16:299–308 Parwani AV, Geradts J, Caspers E, Offerhaus GJ, Yeo CJ, Cameron JL, Klimstra DS, Maitra A, Hruban RH, Argani P (2003) Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions. Mod Pathol 16:299–308
25.
go back to reference Ribieras S, Lefebvre O, Tomasetto C, Rio MC (2001) Mouse Trefoil factor genes: genomic organization, sequences and methylation analyses. Gene 266:67–75 Ribieras S, Lefebvre O, Tomasetto C, Rio MC (2001) Mouse Trefoil factor genes: genomic organization, sequences and methylation analyses. Gene 266:67–75
26.
go back to reference Roa I, Araya JC, Villaseca M, de Artxabala X, Ferreira A, Roa JC (1995) Gallbladder cancer: immunohistochemical expression of the protein related to estrogen receptor (p29) and of the protein induced by estrogen (pS2). Rev Med Chile 123:1333–1340 Roa I, Araya JC, Villaseca M, de Artxabala X, Ferreira A, Roa JC (1995) Gallbladder cancer: immunohistochemical expression of the protein related to estrogen receptor (p29) and of the protein induced by estrogen (pS2). Rev Med Chile 123:1333–1340
27.
go back to reference Rodrigues S, van Aken E, van Bocxlaer S, Attoub S, Nguyen QD, Bruyneel E, Westley BR, May FEB, Thim L, Mareel M, Gespach C, Enami S (2003) Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cyclooxygenase-2 and EGF receptor signaling. FASEB J 17:7–16CrossRefPubMed Rodrigues S, van Aken E, van Bocxlaer S, Attoub S, Nguyen QD, Bruyneel E, Westley BR, May FEB, Thim L, Mareel M, Gespach C, Enami S (2003) Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cyclooxygenase-2 and EGF receptor signaling. FASEB J 17:7–16CrossRefPubMed
28.
go back to reference Rodrigues S, Attoub S, Nguyen QD, Bruyneel E, Rodrigue CM, Westley BR, May FEB, Thim L, Mareel M, Emami S, Gespach C (2003) Selective abrogation of the proinvasive activity of the trefoil peptides pS2 and spasmolytic polypeptide by disruption of the EGF receptor signaling pathways in kidney and colonic cancer cells. Oncogene 22:4488–4497CrossRefPubMed Rodrigues S, Attoub S, Nguyen QD, Bruyneel E, Rodrigue CM, Westley BR, May FEB, Thim L, Mareel M, Emami S, Gespach C (2003) Selective abrogation of the proinvasive activity of the trefoil peptides pS2 and spasmolytic polypeptide by disruption of the EGF receptor signaling pathways in kidney and colonic cancer cells. Oncogene 22:4488–4497CrossRefPubMed
29.
go back to reference Sagol O, Tuna B, Coker A, Karademir S, Obuz F, Astarcioglu H, Kupelioglu A, Astracioglu I, Topalak O (2002) Immunohistochemical detection of pS2 protein and heat shock protein-70 in pancreatic adenocarcinomas. Relationship with disease extent and patient survival. Pathol Res Pract 198:77–84 Sagol O, Tuna B, Coker A, Karademir S, Obuz F, Astarcioglu H, Kupelioglu A, Astracioglu I, Topalak O (2002) Immunohistochemical detection of pS2 protein and heat shock protein-70 in pancreatic adenocarcinomas. Relationship with disease extent and patient survival. Pathol Res Pract 198:77–84
30.
go back to reference Sasaki M, Tsuneyama K, Nakanuma Y (2003) Aberrant expression of trefoil factor family 1 in biliary epithelium in hepatolithiasis and cholangiocarcinoma. Lab Invest 83:1403–1413 Sasaki M, Tsuneyama K, Nakanuma Y (2003) Aberrant expression of trefoil factor family 1 in biliary epithelium in hepatolithiasis and cholangiocarcinoma. Lab Invest 83:1403–1413
31.
go back to reference Seitz G, Thelsinger B, Tomasetto G, Rio MC, Chambon P, Blin N, Welter G (1991) Breast cancer—associated protein pS2 expression in tumors of the biliary tract. Am J Gastroenterol 86:1491–1494 Seitz G, Thelsinger B, Tomasetto G, Rio MC, Chambon P, Blin N, Welter G (1991) Breast cancer—associated protein pS2 expression in tumors of the biliary tract. Am J Gastroenterol 86:1491–1494
32.
go back to reference Sobin LH, Wittekind C (eds) (2002) TNM classification of malignant tumors, 6th edn. Wiley-Liss, New York Sobin LH, Wittekind C (eds) (2002) TNM classification of malignant tumors, 6th edn. Wiley-Liss, New York
33.
go back to reference Srivatsa G, Giraud AS, Ulaganathan M, Yeomans ND, Dow C, Nicoll AJ (2002) Biliary epithelial trefoil peptide expression is increased in biliary diseases. Histopathology 40:262–268 Srivatsa G, Giraud AS, Ulaganathan M, Yeomans ND, Dow C, Nicoll AJ (2002) Biliary epithelial trefoil peptide expression is increased in biliary diseases. Histopathology 40:262–268
34.
go back to reference Suarez C, Vizoso F, Rodriguez JC, Garcia I, Raigoso P, Allende MT, Garcia-Muniz JL, Garcia-Moran M (2001) Prognostic significance of cytosolic pS2 protein content in gastric cancer. Int J Biol Markers 16:37–44 Suarez C, Vizoso F, Rodriguez JC, Garcia I, Raigoso P, Allende MT, Garcia-Muniz JL, Garcia-Moran M (2001) Prognostic significance of cytosolic pS2 protein content in gastric cancer. Int J Biol Markers 16:37–44
35.
go back to reference Taupin D, Podolsky DK (2003) Trefoil factors: initiators of mucosal healing. Nat Rev Mol Cell Biol 4:721–732 Taupin D, Podolsky DK (2003) Trefoil factors: initiators of mucosal healing. Nat Rev Mol Cell Biol 4:721–732
36.
go back to reference Tazuma S, Kajiyama G (2001) Carcinogenesis of malignant lesions of the gallbladder. The impact of chronic inflammation and gallstones. Langenbeck’s Arch Surg 386:224–229 Tazuma S, Kajiyama G (2001) Carcinogenesis of malignant lesions of the gallbladder. The impact of chronic inflammation and gallstones. Langenbeck’s Arch Surg 386:224–229
37.
go back to reference Tomasetto C, Masson R, Linares JL, Wendling C, Lefevre O, Chenard MP, Rio MC (2000) pS2/TFF1 interacts directly with the VWFC cysteine-rich domains of mucins. Gastroenterology 118:70–80 Tomasetto C, Masson R, Linares JL, Wendling C, Lefevre O, Chenard MP, Rio MC (2000) pS2/TFF1 interacts directly with the VWFC cysteine-rich domains of mucins. Gastroenterology 118:70–80
Metadata
Title
Analysis of trefoil factor family protein 1 (TFF1, pS2) expression in chronic cholecystitis and gallbladder carcinoma
Authors
Peter Kornprat
Peter Rehak
Martina Lemmerer
Margit Gogg-Kamerer
Cord Langner
Publication date
01-05-2005
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 5/2005
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-005-1240-4

Other articles of this Issue 5/2005

Virchows Archiv 5/2005 Go to the issue

Announcements

May 2005