Skip to main content
Erschienen in: Head and Neck Pathology 4/2021

11.04.2021 | Original Paper

Immunohistochemical Expression of Fatty Acid Synthase (FASN) is Correlated to Tumor Aggressiveness and Cellular Differentiation in Salivary Gland Carcinomas

verfasst von: Camila Matsunaga de Angelis, Reydson Alcides de Lima-Souza, João Figueira Scarini, Erika Said Abu Egal, Gleyson Kleber do Amaral-Silva, Rogério de Oliveira Gondak, Oslei Paes de Almeida, Carlos Takahiro Chone, Luiz Paulo Kowalski, Albina Altemani, Fernanda Viviane Mariano

Erschienen in: Head and Neck Pathology | Ausgabe 4/2021

Einloggen, um Zugang zu erhalten

Abstract

Fatty acid synthase (FASN) expression is closely related to cancer progression, in particular, tumor aggressiveness and poor prognosis. This study aimed to analyse the expression of FASN in carcinomas of the salivary glands and correlate it with Ki-67 expression. We analysed by immunohistochemistry the expression of FASN and Ki‐67 on tissue sections from 7 cases of adenocarcinoma, not otherwise specified (AdNOS), 6 cases of polymorphous adenocarcinoma (PAC), 16 cases of acinic cell carcinoma (AcCC), 19 cases of adenoid cystic carcinoma (AdCC), 15 cases of epithelial-myoepithelial carcinoma (EMC); 10 cases of secretory carcinoma (SC), 13 cases of mucoepidermoid carcinoma (MEC), 10 cases of salivary duct carcinoma (SDC) and 7 cases of myoepithelial carcinoma (MC). These carcinomas were classified into aggressive and indolent regarding their biological behaviour. Additionally, MEC and AdCC were also classified according to the histological grade. High expression of FASN was found in SDC (100%), SC (100%), AcCC (68.7%) and AdNOS (57.2%). No association was found between FASN and Ki-67 expression. Aggressive carcinomas showed a higher rate of Ki-67 proliferation (p < 0.001) and greater expression of FASN when compared to indolent carcinomas (p < 0.05). With regards to carcinomas categorized as indolent, FASN expression was much higher in the lesions that presented cell differentiation (SC and AcCC). Also, FASN expression was significantly higher in high-grade AdCC and MEC when compared to low-grade tumors (p < 0.05). We concluded that FASN expression was correlated to tumor aggressiveness and cellular differentiation in salivary gland carcinomas.
Literatur
1.
Zurück zum Zitat Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016;23:27–47.CrossRef Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016;23:27–47.CrossRef
2.
Zurück zum Zitat Warburg O, Posener K, Negelein E. Über den Stoffwechsel der Carcinomzelle. Biochem Zeitschr. 1924;152:309–44. Warburg O, Posener K, Negelein E. Über den Stoffwechsel der Carcinomzelle. Biochem Zeitschr. 1924;152:309–44.
3.
Zurück zum Zitat Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519–30.CrossRef Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519–30.CrossRef
4.
Zurück zum Zitat Weljie AM, Jirik FR. Hypoxia-induced metabolic shifts in cancer cells: moving beyond the Warburg effect. Int J Biochem Cell Biol. 2011;43:981–9.CrossRef Weljie AM, Jirik FR. Hypoxia-induced metabolic shifts in cancer cells: moving beyond the Warburg effect. Int J Biochem Cell Biol. 2011;43:981–9.CrossRef
5.
Zurück zum Zitat Garber K. Energy boost: the Warburg effect returns in a new theory of cancer. J Natl Cancer Inst. 2004;96:1805–6.CrossRef Garber K. Energy boost: the Warburg effect returns in a new theory of cancer. J Natl Cancer Inst. 2004;96:1805–6.CrossRef
6.
Zurück zum Zitat Shaw RJ. Glucose metabolism and cancer. Curr Opin Cell Biol. 2006;18:598–608.CrossRef Shaw RJ. Glucose metabolism and cancer. Curr Opin Cell Biol. 2006;18:598–608.CrossRef
7.
Zurück zum Zitat Burns JS, Manda G. Metabolic Pathways of the Warburg Effect in Health and Disease: Perspectives of Choice, Chain or Chance. Int J Mol Sci. 2017;18:2755.CrossRef Burns JS, Manda G. Metabolic Pathways of the Warburg Effect in Health and Disease: Perspectives of Choice, Chain or Chance. Int J Mol Sci. 2017;18:2755.CrossRef
8.
Zurück zum Zitat Kuhajda FP. Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition. 2000;16:202–8.CrossRef Kuhajda FP. Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition. 2000;16:202–8.CrossRef
9.
Zurück zum Zitat Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 2007;7:763–77.CrossRef Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 2007;7:763–77.CrossRef
10.
Zurück zum Zitat Flavin R, Peluso S, Nguyen PL, Loda M. Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol. 2010;6:551–62.CrossRef Flavin R, Peluso S, Nguyen PL, Loda M. Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol. 2010;6:551–62.CrossRef
11.
Zurück zum Zitat Milgraum LZ, Witters LA, Pasternack GR, Kuhajda FP. Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin Cancer Res. 1997;3:2115–20.PubMed Milgraum LZ, Witters LA, Pasternack GR, Kuhajda FP. Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin Cancer Res. 1997;3:2115–20.PubMed
12.
Zurück zum Zitat Chirala SS, Chang H, Matzuk M, Abu-Elheiga L, Mao J, Mahon K, et al. Fatty acid synthesis is essential in embryonic development: fatty acid synthase null mutants and most of the heterozygotes die in utero. Proc Natl Acad Sci U S A. 2003;100:6358–63.CrossRef Chirala SS, Chang H, Matzuk M, Abu-Elheiga L, Mao J, Mahon K, et al. Fatty acid synthesis is essential in embryonic development: fatty acid synthase null mutants and most of the heterozygotes die in utero. Proc Natl Acad Sci U S A. 2003;100:6358–63.CrossRef
13.
Zurück zum Zitat Weiss L, Hoffmann GE, Schreiber R, Andres H, Fuchs E, Körber E, et al. Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase. Biol Chem Hoppe Seyler. 1986;367:905–12.CrossRef Weiss L, Hoffmann GE, Schreiber R, Andres H, Fuchs E, Körber E, et al. Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase. Biol Chem Hoppe Seyler. 1986;367:905–12.CrossRef
14.
Zurück zum Zitat Baron A, Migita T, Tang D, Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer? J Cell Biochem. 2004;91:47–53.CrossRef Baron A, Migita T, Tang D, Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer? J Cell Biochem. 2004;91:47–53.CrossRef
15.
Zurück zum Zitat Alò PL, Visca P, Framarino ML, Botti C, Monaco S, Sebastiani V, et al. Immunohistochemical study of fatty acid synthase in ovarian neoplasms. Oncol Rep. 2000;7:1383–8.PubMed Alò PL, Visca P, Framarino ML, Botti C, Monaco S, Sebastiani V, et al. Immunohistochemical study of fatty acid synthase in ovarian neoplasms. Oncol Rep. 2000;7:1383–8.PubMed
16.
Zurück zum Zitat Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K, et al. Delineation of prognostic biomarkers in prostate cancer. Nature. 2001;412:822–6.CrossRef Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K, et al. Delineation of prognostic biomarkers in prostate cancer. Nature. 2001;412:822–6.CrossRef
17.
Zurück zum Zitat Swinnen JV, Roskams T, Joniau S, Van Poppel H, Oyen R, Baert L, et al. Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer. 2002;98:19–22. CrossRef Swinnen JV, Roskams T, Joniau S, Van Poppel H, Oyen R, Baert L, et al. Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer. 2002;98:19–22.  CrossRef
18.
Zurück zum Zitat Piyathilake CJ, Frost AR, Manne U, Bell WC, Weiss H, Heimburger DC, et al. The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung. Hum Pathol. 2000;31:1068–73.CrossRef Piyathilake CJ, Frost AR, Manne U, Bell WC, Weiss H, Heimburger DC, et al. The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung. Hum Pathol. 2000;31:1068–73.CrossRef
19.
Zurück zum Zitat Nemoto T, Terashima S, Kogure M, Hoshino Y, Kusakabe T, Suzuki T, et al. Overexpression of fatty acid synthase in oesophageal squamous cell dysplasia and carcinoma. Pathobiology. 2001;69:297–303.CrossRef Nemoto T, Terashima S, Kogure M, Hoshino Y, Kusakabe T, Suzuki T, et al. Overexpression of fatty acid synthase in oesophageal squamous cell dysplasia and carcinoma. Pathobiology. 2001;69:297–303.CrossRef
20.
Zurück zum Zitat Kusakabe T, Nashimoto A, Honma K, Suzuki T. Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach. Histopathology. 2002;40:71–9.CrossRef Kusakabe T, Nashimoto A, Honma K, Suzuki T. Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach. Histopathology. 2002;40:71–9.CrossRef
21.
Zurück zum Zitat Visca P, Sebastiani V, Pizer ES, Botti C, De Carli P, Filippi S, et al. Immunohistochemical expression and prognostic significance of FAS and GLUT1 in bladder carcinoma. Anticancer Res. 2003;23:335–9.PubMed Visca P, Sebastiani V, Pizer ES, Botti C, De Carli P, Filippi S, et al. Immunohistochemical expression and prognostic significance of FAS and GLUT1 in bladder carcinoma. Anticancer Res. 2003;23:335–9.PubMed
22.
Zurück zum Zitat Agostini M, Silva SD, Zecchin KG, Coletta RD, Jorge J, Loda M, et al. Fatty acid synthase is required for the proliferation of human oral squamous carcinoma cells. Oral Oncol. 2004;40:728–35.CrossRef Agostini M, Silva SD, Zecchin KG, Coletta RD, Jorge J, Loda M, et al. Fatty acid synthase is required for the proliferation of human oral squamous carcinoma cells. Oral Oncol. 2004;40:728–35.CrossRef
23.
Zurück zum Zitat Horiguchi A, Asano T, Asano T, Ito K, Sumitomo M, Hayakawa M. Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma. J Urol. 2008;180:1137–40.CrossRef Horiguchi A, Asano T, Asano T, Ito K, Sumitomo M, Hayakawa M. Fatty acid synthase over expression is an indicator of tumor aggressiveness and poor prognosis in renal cell carcinoma. J Urol. 2008;180:1137–40.CrossRef
24.
Zurück zum Zitat Ito FA, Ito K, Coletta RD, Graner E, de Almeida OP, Lopes MA. Salivary gland tumors: immunohistochemical study of EGF, EGFR, ErbB-2, FAS and Ki-67. Anal Quant Cytol Histol. 2009;31:280–7.PubMed Ito FA, Ito K, Coletta RD, Graner E, de Almeida OP, Lopes MA. Salivary gland tumors: immunohistochemical study of EGF, EGFR, ErbB-2, FAS and Ki-67. Anal Quant Cytol Histol. 2009;31:280–7.PubMed
25.
Zurück zum Zitat do Prado RF, da Machado SAL, Colombo CED, Carvalho YR. Immunohistochemical study of the expression of fatty acid synthase and Ki-67 in salivary gland tumors. J Oral Pathol Med. 2011;40:467–75.CrossRef do Prado RF, da Machado SAL, Colombo CED, Carvalho YR. Immunohistochemical study of the expression of fatty acid synthase and Ki-67 in salivary gland tumors. J Oral Pathol Med. 2011;40:467–75.CrossRef
26.
Zurück zum Zitat Díaz KP, Gondak R, Martins LL, de Almeida OP, León JE, Mariano FV, et al. Fatty acid synthase and Ki-67 immunoexpression can be useful for the identification of malignant component in carcinoma ex-pleomorphic adenoma. J Oral Pathol Med. 2019;48:232–8.CrossRef Díaz KP, Gondak R, Martins LL, de Almeida OP, León JE, Mariano FV, et al. Fatty acid synthase and Ki-67 immunoexpression can be useful for the identification of malignant component in carcinoma ex-pleomorphic adenoma. J Oral Pathol Med. 2019;48:232–8.CrossRef
27.
Zurück zum Zitat Scarini JF, Rosa LF, de Souza RAL, Egal ESA, Tincani AJ, Martins AS, et al. Gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development. Oral Dis. 2020;26:1190–9.CrossRef Scarini JF, Rosa LF, de Souza RAL, Egal ESA, Tincani AJ, Martins AS, et al. Gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development. Oral Dis. 2020;26:1190–9.CrossRef
28.
Zurück zum Zitat Currie E, Schulze A, Zechner R, Walther TC, Farese RV. Cellular fatty acid metabolism and cancer. Cell Metab. 2013;18:153–61.CrossRef Currie E, Schulze A, Zechner R, Walther TC, Farese RV. Cellular fatty acid metabolism and cancer. Cell Metab. 2013;18:153–61.CrossRef
29.
Zurück zum Zitat El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. WHO classification of head and neck tumours. 4th ed. France: International Agency for Research on Cancer (IARC); 2017. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. WHO classification of head and neck tumours. 4th ed. France: International Agency for Research on Cancer (IARC); 2017.
30.
Zurück zum Zitat Mariano FV, dos Santos HT, Azañero WD, da Cunha IW, Coutinho-Camilo CM, de Almeida OP, et al. Mammary analogue secretory carcinoma of salivary glands is a lipid-rich tumour, and adipophilin can be valuable in its identification. Histopathology. 2013;63:558–67.PubMed Mariano FV, dos Santos HT, Azañero WD, da Cunha IW, Coutinho-Camilo CM, de Almeida OP, et al. Mammary analogue secretory carcinoma of salivary glands is a lipid-rich tumour, and adipophilin can be valuable in its identification. Histopathology. 2013;63:558–67.PubMed
31.
Zurück zum Zitat da Silva SD, Cunha IW, Nishimoto IN, Soares FA, Carraro DM, Kowalski LP, et al. Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas. Oral Oncol. 2009;45:e134–9.CrossRef da Silva SD, Cunha IW, Nishimoto IN, Soares FA, Carraro DM, Kowalski LP, et al. Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas. Oral Oncol. 2009;45:e134–9.CrossRef
32.
Zurück zum Zitat de Andrade BAB, León JE, Carlos R, Delgado-Azañero W, Mosqueda-Taylor A, Graner E, et al. Expression of fatty acid synthase (FASN) in oral nevi and melanoma. Oral Dis. 2011;17:808–12.CrossRef de Andrade BAB, León JE, Carlos R, Delgado-Azañero W, Mosqueda-Taylor A, Graner E, et al. Expression of fatty acid synthase (FASN) in oral nevi and melanoma. Oral Dis. 2011;17:808–12.CrossRef
33.
Zurück zum Zitat Allina DO, Andreeva YY, Zavalishina LE, Moskvina LV, Frank GA. Fatty acid synthase in the diagnosis of prostate neoplasms. Arkh Patol. 2017;79:10–4.CrossRef Allina DO, Andreeva YY, Zavalishina LE, Moskvina LV, Frank GA. Fatty acid synthase in the diagnosis of prostate neoplasms. Arkh Patol. 2017;79:10–4.CrossRef
34.
Zurück zum Zitat Hirai H, Tada Y, Nakaguro M, Kawakita D, Sato Y, Shimura T, et al. The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma. Virchows Arch. 2020;477:291–9.CrossRef Hirai H, Tada Y, Nakaguro M, Kawakita D, Sato Y, Shimura T, et al. The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma. Virchows Arch. 2020;477:291–9.CrossRef
35.
Zurück zum Zitat Suburu J, Shi L, Wu J, Wang S, Samuel M, Thomas MJ, et al. Fatty acid synthase is required for mammary gland development and milk production during lactation. Am J Physiol Endocrinol Metab. 2014;306:E1132–43.CrossRef Suburu J, Shi L, Wu J, Wang S, Samuel M, Thomas MJ, et al. Fatty acid synthase is required for mammary gland development and milk production during lactation. Am J Physiol Endocrinol Metab. 2014;306:E1132–43.CrossRef
36.
Zurück zum Zitat Vander Poorten V, Triantafyllou A, Thompson LDR, Bishop J, Hauben E, Hunt J, et al. Salivary acinic cell carcinoma: reappraisal and update. Eur Arch Otorhinolaryngol. 2016;273:3511–31.CrossRef Vander Poorten V, Triantafyllou A, Thompson LDR, Bishop J, Hauben E, Hunt J, et al. Salivary acinic cell carcinoma: reappraisal and update. Eur Arch Otorhinolaryngol. 2016;273:3511–31.CrossRef
37.
Zurück zum Zitat Brasaemle DL, Barber T, Wolins NE, Serrero G, Blanchette-Mackie EJ, Londos C. Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein. J Lipid Res. 1997;38:2249–63.CrossRef Brasaemle DL, Barber T, Wolins NE, Serrero G, Blanchette-Mackie EJ, Londos C. Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein. J Lipid Res. 1997;38:2249–63.CrossRef
38.
Zurück zum Zitat Menendez JA, Vellon L, Lupu R. Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann Oncol. 2005;16:1253–67.CrossRef Menendez JA, Vellon L, Lupu R. Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene. Ann Oncol. 2005;16:1253–67.CrossRef
Metadaten
Titel
Immunohistochemical Expression of Fatty Acid Synthase (FASN) is Correlated to Tumor Aggressiveness and Cellular Differentiation in Salivary Gland Carcinomas
verfasst von
Camila Matsunaga de Angelis
Reydson Alcides de Lima-Souza
João Figueira Scarini
Erika Said Abu Egal
Gleyson Kleber do Amaral-Silva
Rogério de Oliveira Gondak
Oslei Paes de Almeida
Carlos Takahiro Chone
Luiz Paulo Kowalski
Albina Altemani
Fernanda Viviane Mariano
Publikationsdatum
11.04.2021
Verlag
Springer US
Erschienen in
Head and Neck Pathology / Ausgabe 4/2021
Elektronische ISSN: 1936-0568
DOI
https://doi.org/10.1007/s12105-021-01319-3

Weitere Artikel der Ausgabe 4/2021

Head and Neck Pathology 4/2021 Zur Ausgabe

Sine qua non Radiology-Pathology

Sine Qua Non: Dentigerous Cyst

Neu im Fachgebiet Pathologie

Assistierter Suizid durch Infusion von Thiopental

Thiopental Originalie

Als Folge des Urteils des Bundesverfassungsgerichts zur Sterbehilfe im Jahr 2020 wurde in den Jahren 2021–2023 eine Reihe (n = 23) von assistierten Suiziden im Landesinstitut für gerichtliche und soziale Medizin Berlin mit jeweils identischen …

Molekularpathologische Untersuchungen im Wandel der Zeit

Open Access Biomarker Leitthema

Um auch an kleinen Gewebeproben zuverlässige und reproduzierbare Ergebnisse zu gewährleisten ist eine strenge Qualitätskontrolle in jedem Schritt des Arbeitsablaufs erforderlich. Eine nicht ordnungsgemäße Prüfung oder Behandlung des …

Vergleichende Pathologie in der onkologischen Forschung

Pathologie Leitthema

Die vergleichende experimentelle Pathologie („comparative experimental pathology“) ist ein Fachbereich an der Schnittstelle von Human- und Veterinärmedizin. Sie widmet sich der vergleichenden Erforschung von Gemeinsamkeiten und Unterschieden von …

Gastrointestinale Stromatumoren

Open Access GIST CME-Artikel

Gastrointestinale Stromatumoren (GIST) stellen seit über 20 Jahren ein Paradigma für die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren dar. Eine elementare Voraussetzung für eine mögliche neoadjuvante oder adjuvante Behandlung bei …