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Erschienen in: Journal of Cancer Research and Clinical Oncology 11/2009

01.11.2009 | Original Paper

Evaluation of fatty acid synthase expression in oesophageal mucosa of patients with oesophagitis, Barrett’s oesophagus and adenocarcinoma

verfasst von: Pietro Crispino, Piero Luigi Alò, Margherita Rivera, Domenica Barillà, Francesco Nardi, Mauro Mariotti, Zotti Giancarlo, Claudio Botti, Roberta Pica, Claudio Cassieri, Hans Unim, Paolo Paoluzi

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 11/2009

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Abstract

Background and aim

To evaluate the expression of fatty acid synthase (FAS) in the oesophagitis–Barrett’s oesophagus–oesophageal adenocarcinoma sequence compared with p53 and Ki67 expressions, retained for a long time reliable markers of oesophageal cells biological behaviour.

Methods

In Barrett’s oesophagus, oesophagitis and oesophageal adenocarcinoma patients, biopsies were taken from pathologic sites of the mucosa for histological and immuno-histochemical detection of FAS, p53 and Ki67. FAS expression was positive, when a strong granular cytoplasmic staining was observed in oesophageal cells. Ki67 and p53 was defined positive, when nuclear staining was clearly detected at 10× magnification.

Results

A mild expression of FAS was found in 39% of patients with oesophagitis. The amount of FAS expression increased up to 70% in Barrett’s oesophagus while this was present in all patients with oesophageal adenocarcinoma (p = 0.0001). In Barrett’s oesophagus, p53 was mildly or intensely expressed in 77% and in 15% of cases, respectively, and mildly or intensely expressed in 33% and 67% of patients with oesophageal adenocarcinoma, respectively, (p = 0.0001). Ki67 was mildly expressed in 17% of oesophagitis cases and was absent in the majority of cases. In Barrett’s oesophagus, a mild Ki67 expression was present in 46% of cases, and in oesophageal adenocarcinoma it was present prevalently in intense form (67%; p = 0.0001).

Conclusions

The over-expression of p53, Ki67 and FAS in otherwise similar morphological groups may be useful to stratify patients into selected prognostic subgroups in order to achieve better clinical approaches.
Literatur
Zurück zum Zitat Cameron AJ, Ott BJ, Payne WS (1985) The incidence of adenocarcinoma in columnar-lined (Barrett’s) esophagus. N Engl J Med 313:857–858PubMed Cameron AJ, Ott BJ, Payne WS (1985) The incidence of adenocarcinoma in columnar-lined (Barrett’s) esophagus. N Engl J Med 313:857–858PubMed
Zurück zum Zitat Chalbos D, Joeux C, Galtier F et al (1990) Regulation of fatty acid synthase by progesterone in normal and tumoral human mammary glands. Rev Esp Fisiol 46:43–46PubMed Chalbos D, Joeux C, Galtier F et al (1990) Regulation of fatty acid synthase by progesterone in normal and tumoral human mammary glands. Rev Esp Fisiol 46:43–46PubMed
Zurück zum Zitat Chatelain D, Flejou JF (2003) High-grade dysplasia and superficial adenocarcinoma in Barrett’s esophagus: histological mapping and expression of p53, p21 and Bcl-2 oncoproteins. Virchows Arch 442:18–24PubMed Chatelain D, Flejou JF (2003) High-grade dysplasia and superficial adenocarcinoma in Barrett’s esophagus: histological mapping and expression of p53, p21 and Bcl-2 oncoproteins. Virchows Arch 442:18–24PubMed
Zurück zum Zitat Drewitz DJ, Sampliner RE, Garewal HS (1997) The incidence of adenocarcinoma in Barrett’s esophagus: a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol 92:212–215PubMed Drewitz DJ, Sampliner RE, Garewal HS (1997) The incidence of adenocarcinoma in Barrett’s esophagus: a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol 92:212–215PubMed
Zurück zum Zitat Flejou JF, Chatelain D (1999) Contribution of new tools to the characterization of Barrett mucosa. Gastroenterol Clin Biol 23:20–29 Flejou JF, Chatelain D (1999) Contribution of new tools to the characterization of Barrett mucosa. Gastroenterol Clin Biol 23:20–29
Zurück zum Zitat Goldblum JR, Lauwers GY (2002) Dysplasia arising in Barrett’s esophagus: diagnostic pitfalls and natural history. Semin Diagn Pathol 19:12–19PubMed Goldblum JR, Lauwers GY (2002) Dysplasia arising in Barrett’s esophagus: diagnostic pitfalls and natural history. Semin Diagn Pathol 19:12–19PubMed
Zurück zum Zitat Hameeteman W, Tytgat GNJ, Houthoff HJ et al (1989) Barrett’s esophagus: development of dysplasia and adenocarcinoma. Gastroenterology 96:1249–1256PubMed Hameeteman W, Tytgat GNJ, Houthoff HJ et al (1989) Barrett’s esophagus: development of dysplasia and adenocarcinoma. Gastroenterology 96:1249–1256PubMed
Zurück zum Zitat Hamilton SR, Aaltonen LA (2000) WHO pathology and genetics: tumors of digestive system. IARC Press, Lyon Hamilton SR, Aaltonen LA (2000) WHO pathology and genetics: tumors of digestive system. IARC Press, Lyon
Zurück zum Zitat Jankowski JA, Wright NA, Meltzer SJ et al (1999) Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol 154:965–973PubMed Jankowski JA, Wright NA, Meltzer SJ et al (1999) Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol 154:965–973PubMed
Zurück zum Zitat Kim R, Weissfeld JL, Reynolds JC et al (1997b) Etiology of Barrett’s esophagus and esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev 6:369–377PubMed Kim R, Weissfeld JL, Reynolds JC et al (1997b) Etiology of Barrett’s esophagus and esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev 6:369–377PubMed
Zurück zum Zitat Levine DS, Haggitt RC, Blount PL et al (1993) An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus. Gastroenterology 105:40–50PubMed Levine DS, Haggitt RC, Blount PL et al (1993) An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus. Gastroenterology 105:40–50PubMed
Zurück zum Zitat Levine DS, Haggitt RC, Irvine S (1996) Natural history of high-grade dysplasia in Barrett’s esophagus. Gastroenterology 110:A550 Levine DS, Haggitt RC, Irvine S (1996) Natural history of high-grade dysplasia in Barrett’s esophagus. Gastroenterology 110:A550
Zurück zum Zitat Li JN, Gorospe M, Chrest JC, Kumaravel TS, Evans MK, Han WF, Pizer ES (2001) Pharmacological inhibition of fatty acid synthase activity produces cytostatic and cytotoxic effects modulated by p53. Cancer Res 61:1493–1499PubMed Li JN, Gorospe M, Chrest JC, Kumaravel TS, Evans MK, Han WF, Pizer ES (2001) Pharmacological inhibition of fatty acid synthase activity produces cytostatic and cytotoxic effects modulated by p53. Cancer Res 61:1493–1499PubMed
Zurück zum Zitat Lundell L, Dent J, Bennett J et al (1999) Endoscopic assessment of esophagitis: clinical and functional correlates and further validation of the Los Angeles Classification. Gut 45:172–180PubMedCrossRef Lundell L, Dent J, Bennett J et al (1999) Endoscopic assessment of esophagitis: clinical and functional correlates and further validation of the Los Angeles Classification. Gut 45:172–180PubMedCrossRef
Zurück zum Zitat Montgomery E, Goldblum JR, Greenson JK et al (2001) Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study. Hum Pathol 32:379–388. doi:10.1053/hupa.2001.23511 PubMedCrossRef Montgomery E, Goldblum JR, Greenson JK et al (2001) Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study. Hum Pathol 32:379–388. doi:10.​1053/​hupa.​2001.​23511 PubMedCrossRef
Zurück zum Zitat Nemoto T, Terashima S, Kogure M, Hoshino Y, Kusakabe T, Suzuki T, Gotoh M (2001) Overexpression of fatty acid synthase in oesophageal squamous cell dysplasia and carcinoma. Pathobiology 69(6):297–303. doi:10.1159/000064636 PubMedCrossRef Nemoto T, Terashima S, Kogure M, Hoshino Y, Kusakabe T, Suzuki T, Gotoh M (2001) Overexpression of fatty acid synthase in oesophageal squamous cell dysplasia and carcinoma. Pathobiology 69(6):297–303. doi:10.​1159/​000064636 PubMedCrossRef
Zurück zum Zitat Paulaskis JD, Sul HS (1989) Hormonal regulation of mouse fatty acid synthase gene trascription in liver. J Biol Chem 264:574–577 Paulaskis JD, Sul HS (1989) Hormonal regulation of mouse fatty acid synthase gene trascription in liver. J Biol Chem 264:574–577
Zurück zum Zitat Pizer ES, Jackisch C, Wood FD, Pasternack GR, Davidson NE, Kuhajda FP (1996) Inibition of fatty acid synthasis induces programmed cell death in human breast cancer cells. Cancer Res 56:2745–2747PubMed Pizer ES, Jackisch C, Wood FD, Pasternack GR, Davidson NE, Kuhajda FP (1996) Inibition of fatty acid synthasis induces programmed cell death in human breast cancer cells. Cancer Res 56:2745–2747PubMed
Zurück zum Zitat Rashid A, Pizer ES, Moga M et al (1997) Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol 150:201–208PubMed Rashid A, Pizer ES, Moga M et al (1997) Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol 150:201–208PubMed
Zurück zum Zitat Robertson CS, Mayberry JF, Nicholson DA et al (1988) Value of endoscopic surveillance in the detection of neoplastic change in Barrett’s esophagus. Br J Surg 72:760–763. doi:10.1002/bjs.1800750813 CrossRef Robertson CS, Mayberry JF, Nicholson DA et al (1988) Value of endoscopic surveillance in the detection of neoplastic change in Barrett’s esophagus. Br J Surg 72:760–763. doi:10.​1002/​bjs.​1800750813 CrossRef
Zurück zum Zitat Sharma P, Reker D, Falk G et al (2001) Progression of Barrett’s esophagus to high-grade dysplasia and cancer—preliminary results of the Barrett’s esophagus study trial. Gastroenterology 120:A16 Sharma P, Reker D, Falk G et al (2001) Progression of Barrett’s esophagus to high-grade dysplasia and cancer—preliminary results of the Barrett’s esophagus study trial. Gastroenterology 120:A16
Zurück zum Zitat Smith S (1994) The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J 8:1248–1259PubMed Smith S (1994) The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J 8:1248–1259PubMed
Zurück zum Zitat Spechler SJ, Robbins AH, Rubins HB et al (1984) Adenocarcinoma and Barrett’s esophagus. An overrated risk. Gastroenterology 87:927–933PubMed Spechler SJ, Robbins AH, Rubins HB et al (1984) Adenocarcinoma and Barrett’s esophagus. An overrated risk. Gastroenterology 87:927–933PubMed
Zurück zum Zitat Visca P, Sebastiani V, Botti C et al (2004) Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma. Anticancer Res 24:4169–4173PubMed Visca P, Sebastiani V, Botti C et al (2004) Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma. Anticancer Res 24:4169–4173PubMed
Zurück zum Zitat Weiss L, Hoffmann GE, Schreiber R, Andres H, Fuchs E, Korber E, Kolb HJ (1986) Fatty acid biosynthesis in man, a pathway of minor importance. Biol Chem Hoppe Seyler 367:905–912PubMed Weiss L, Hoffmann GE, Schreiber R, Andres H, Fuchs E, Korber E, Kolb HJ (1986) Fatty acid biosynthesis in man, a pathway of minor importance. Biol Chem Hoppe Seyler 367:905–912PubMed
Zurück zum Zitat Werner M, Mueleer J, Walch A et al (1999) The molecular pathology of Barrett’s esophagus. Histol Histopathol 14:553–559PubMed Werner M, Mueleer J, Walch A et al (1999) The molecular pathology of Barrett’s esophagus. Histol Histopathol 14:553–559PubMed
Zurück zum Zitat Weston AP, Badr AS, Hassanein RS (1999) Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett’s multifocal high-grade dysplasia or adenocarcinoma. Am J Gastroenterol 94:3413–3419. doi:10.1111/j.1572-0241.1999.01602.x PubMedCrossRef Weston AP, Badr AS, Hassanein RS (1999) Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett’s multifocal high-grade dysplasia or adenocarcinoma. Am J Gastroenterol 94:3413–3419. doi:10.​1111/​j.​1572-0241.​1999.​01602.​x PubMedCrossRef
Metadaten
Titel
Evaluation of fatty acid synthase expression in oesophageal mucosa of patients with oesophagitis, Barrett’s oesophagus and adenocarcinoma
verfasst von
Pietro Crispino
Piero Luigi Alò
Margherita Rivera
Domenica Barillà
Francesco Nardi
Mauro Mariotti
Zotti Giancarlo
Claudio Botti
Roberta Pica
Claudio Cassieri
Hans Unim
Paolo Paoluzi
Publikationsdatum
01.11.2009
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 11/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-009-0600-x

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