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Expression of metabolism-related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma

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Tumor Biology

Abstract

The purpose of this study is to investigate the difference in expression of metabolism-related proteins in invasive lobular carcinoma (ILC) compared to those of the invasive ductal carcinoma (IDC). Tissue microarray was manufactured for 114 cases of ILC and 692 cases of IDC. Immunohistochemical stains were performed as follows: glycolysis (Glut-1, hexokinase II, CAIX, MCT4), glutaminolysis (GLS1, GDH, ASCT2), mitochondria (ATP synthase, SDHA, SDHB), and serine/glycine metabolism (PHGDH, PSAT1, PSPH, SHMT1, GLDC) related proteins. Pleomorphic type (n = 12) of ILC revealed higher expression in hexokinase II, SDHB, and GLDC than classic type (n = 102) (p < 0.05). IDC showed a higher expression of glycolysis (Glut-1, CAIX, MCT4), glutaminolysis (GLS1, ASCT2), and serine/glycine metabolism (PSPH, SHMT1, GLDC) related protein than ILC in tumor cells, whereas ILC revealed higher expression in GDH, SDHA, PHGDH, and PSAT1 than IDC in tumor cells (p < 0.05). In addition, IDC demonstrated a higher expression of metabolism-related proteins than ILC in stromal tissue (p < 0.05). In ILC, tumoral GLDC positivity was correlated with higher nuclear grade (p = 0.026) and higher histologic grade (p = 0.026), and tumoral Glut-1 positivity correlated with higher histologic grade (p = 0.026). Additionally, tumoral PSPH positivity showed a significant correlation to ER negativity and PR negativity (p = 0.026). In conclusion, it reveals different expression patterns of metabolism-related proteins between IDC and ILC

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References

  1. Tavassoli FA, Devilee P, International Agency for Research on Cancer, World Health Organization. Pathology and genetics of tumours of the breast and female genital organs. Lyon: IAPS Press; 2003.

    Google Scholar 

  2. Li CI, Chlebowski RT, Freiberg M, Johnson KC, Kuller L, Lane D, et al. Alcohol consumption and risk of postmenopausal breast cancer by subtype: the women’s health initiative observational study. J Natl Cancer Inst. 2010;102:1422–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Reeves GK, Beral V, Green J, Gathani T, Bull D. Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol. 2006;7:910–8.

    Article  CAS  PubMed  Google Scholar 

  4. Sastre-Garau X, Jouve M, Asselain B, Vincent-Salomon A, Beuzeboc P, Dorval T, et al. Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns. Cancer. 1996;77:113–20.

    Article  CAS  PubMed  Google Scholar 

  5. Silverstein MJ, Lewinsky BS, Waisman JR, Gierson ED, Colburn WJ, Senofsky GM, et al. Infiltrating lobular carcinoma. Is it different from infiltrating duct carcinoma? Cancer. 1994;73:1673–7.

    Article  CAS  PubMed  Google Scholar 

  6. Lamovec J, Bracko M. Metastatic pattern of infiltrating lobular carcinoma of the breast: an autopsy study. J Surg Oncol. 1991;48:28–33.

    Article  CAS  PubMed  Google Scholar 

  7. De Leeuw WJ, Berx G, Vos CB, Peterse JL, Van de Vijver MJ, Litvinov S, et al. Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997;183:404–11.

    Article  PubMed  Google Scholar 

  8. Warburg O. On the origin of cancer cells. Science. 1956;123:309–14.

    Article  CAS  PubMed  Google Scholar 

  9. Moreno-Sanchez R, Rodriguez-Enriquez S, Marin-Hernandez A, Saavedra E. Energy metabolism in tumor cells. FEBS J. 2007;274:1393–418.

    Article  CAS  PubMed  Google Scholar 

  10. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.

    Article  CAS  PubMed  Google Scholar 

  11. Kim JW, Dang CV. Cancer's molecular sweet tooth and the Warburg effect. Cancer Res. 2006;66:8927–30.

    Article  CAS  PubMed  Google Scholar 

  12. Kim JW, Gao P, Dang CV. Effects of hypoxia on tumor metabolism. Cancer Metastasis Rev. 2007;26:291–8.

    Article  PubMed  Google Scholar 

  13. Wise DR, Thompson CB. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci. 2010;35:427–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.

    Article  CAS  PubMed  Google Scholar 

  16. Won KY, Kim GY, Kim YW, Song JY, Lim SJ. Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer. Hum Pathol. 2010;41:107–12.

    Article  CAS  PubMed  Google Scholar 

  17. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22:1736–47.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Grover-McKay M, Walsh SA, Seftor EA, Thomas PA, Hendrix MJ. Role for glucose transporter 1 protein in human breast cancer. Pathol Oncol Res. 1998;4:115–20.

    Article  CAS  PubMed  Google Scholar 

  19. Brown RS, Wahl RL. Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study. Cancer. 1993;72:2979–85.

    Article  CAS  PubMed  Google Scholar 

  20. Ravazoula P, Batistatou A, Aletra C, Ladopoulos J, Kourounis G, Tzigounis B. Immunohistochemical expression of glucose transporter Glut1 and cyclin D1 in breast carcinomas with negative lymph nodes. Eur J Gynaecol Oncol. 2003;24:544–6.

    CAS  PubMed  Google Scholar 

  21. Trastour C, Benizri E, Ettore F, Ramaioli A, Chamorey E, Pouyssegur J, et al. HIF-1alpha and CA IX staining in invasive breast carcinomas: prognosis and treatment outcome. Int J Cancer. 2007;120:1451–8.

    Article  CAS  PubMed  Google Scholar 

  22. Alo PL, Visca P, Botti C, Galati GM, Sebastiani V, Andreano T, et al. Immunohistochemical expression of human erythrocyte glucose transporter and fatty acid synthase in infiltrating breast carcinomas and adjacent typical/atypical hyperplastic or normal breast tissue. Am J Clin Pathol. 2001;116:129–34.

    Article  CAS  PubMed  Google Scholar 

  23. Radhi JM. Immunohistochemical analysis of pleomorphic lobular carcinoma: higher expression of p53 and chromogranin and lower expression of ER and PgR. Histopathology. 2000;36:156–60.

    Article  CAS  PubMed  Google Scholar 

  24. Frolik D, Caduff R, Varga Z. Pleomorphic lobular carcinoma of the breast: its cell kinetics, expression of oncogenes and tumour suppressor genes compared with invasive ductal carcinomas and classical infiltrating lobular carcinomas. Histopathology. 2001;39:503–13.

    Article  CAS  PubMed  Google Scholar 

  25. Choi J, Jung WH, Koo JS. Metabolism-related proteins are differentially expressed according to the molecular subtype of invasive breast cancer defined by surrogate immunohistochemistry. Pathobiology. 2013;80:41–52.

    Article  CAS  PubMed  Google Scholar 

  26. Pinheiro C, Sousa B, Albergaria A, Paredes J, Dufloth R, Vieira D, et al. GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression. Histol Histopathol. 2011;26:1279–86.

    CAS  PubMed  Google Scholar 

  27. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.

    Article  CAS  PubMed  Google Scholar 

  28. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Kim S, do Kim H, Jung WH, JS K. Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. Endocr Relat Cancer. 2013;20:339–48.

    Article  CAS  PubMed  Google Scholar 

  30. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, et al. Ketones and lactate "fuel" tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle. 2010;9:3506–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, et al. Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: a new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle. 2010;9:3256–76.

    PubMed Central  CAS  PubMed  Google Scholar 

  32. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Loss of stromal caveolin-1 leads to oxidative stress, mimics hypoxia and drives inflammation in the tumor microenvironment, conferring the "reverse Warburg effect": a transcriptional informatics analysis with validation. Cell Cycle. 2010;9:2201–19.

    Article  CAS  PubMed  Google Scholar 

  33. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle. 2009;8:3984–4001.

    Article  CAS  PubMed  Google Scholar 

  34. Liu Z, Yang Z, Jiang S, Zou Q, Yuan Y, Li J, et al. Paxillin and Carbonic Anhydrase IX are prognostic markers in gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas. Histopathology. 2014;64(7):921–34.

  35. Klimowicz AC, Bose P, Petrillo SK, Magliocco AM, Dort JC, Brockton NT. The prognostic impact of a combined carbonic anhydrase IX and Ki67 signature in oral squamous cell carcinoma. Br J Cancer. 2013;109:1859–66.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Kaya AO, Gunel N, Benekli M, Akyurek N, Buyukberber S, Tatli H, et al. Hypoxia inducible factor-1 alpha and carbonic anhydrase IX overexpression are associated with poor survival in breast cancer patients. J BUON. 2012;17:663–8.

    CAS  PubMed  Google Scholar 

  37. Chang H, Shyu KG, Lee CC, Tsai SC, Wang BW, Hsien Lee Y, et al. GL331 inhibits HIF-1alpha expression in a lung cancer model. Biochem Biophys Res Commun. 2003;302:95–100.

    Article  CAS  PubMed  Google Scholar 

  38. Yeo EJ, Chun YS, Cho YS, Kim J, Lee JC, Kim MS, et al. YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst. 2003;95:516–25.

    Article  CAS  PubMed  Google Scholar 

  39. Mohanti BK, Rath GK, Anantha N, Kannan V, Das BS, Chandramouli BA, et al. Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas. Int J Radiat Oncol Biol Phys. 1996;35:103–11.

    Article  CAS  PubMed  Google Scholar 

  40. Aft RL, Zhang FW, Gius D. Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death. Br J Cancer. 2002;87:805–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Vullo D, Franchi M, Gallori E, Pastorek J, Scozzafava A, Pastorekova S, et al. Carbonic anhydrase inhibitors: inhibition of the tumor-associated isozyme IX with aromatic and heterocyclic sulfonamides. Bioorg Med Chem Lett. 2003;13:1005–9.

    Article  CAS  PubMed  Google Scholar 

  42. Gallagher SM, Castorino JJ, Wang D, Philp NJ. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231. Cancer Res. 2007;67:4182–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A1002886). This study was supported by a grant from National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1420080).

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  1. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Yon Hee Kim, Woo Hee Jung & Ja Seung Koo

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  1. Yon Hee Kim
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Correspondence to Ja Seung Koo.

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Kim, Y.H., Jung, W.H. & Koo, J.S. Expression of metabolism-related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma. Tumor Biol. 35, 10381–10393 (2014). https://doi.org/10.1007/s13277-014-2345-7

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  • DOI: https://doi.org/10.1007/s13277-014-2345-7

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