Iberoamerican Journal of Medicine
https://iberoamjmed.com/article/doi/10.5281/zenodo.4422074
Iberoamerican Journal of Medicine
Original article

Quantitative immunohistochemical expression of GP88 in invasive ductal carcinoma (IDC) of human breast cancer

Mona Abdel-Hamed Yehia, Sabah Ali AL-Qadasi, Amel Sobhey AL-Sedfy

Downloads: 1
Views: 325

Abstract

Introduction: Progranulin or acrogranin is an 88-kDa glycoprotein identified by a biological screen for protein targets associated with high tumorigenicity. This work was aimed to investigate the digital expression of GP88, and HER2/neu as a predictive biomarker in human invasive ductal carcinoma (IDC) versus benign tumors and normal breast tissues, as well as its correlation with different pathological parameters.
Methods: The immunohistochemical avidin-biotin complex protocol of the paraffin section was used to detect the expression of GP88 and HER2/neu in IDC of 60 patients, 30 benign, and ten normal breast tissues.
Results: The study showed a high expression of GP88 in IDC comparing to normal and benign breast tissues. A higher significant statistical correlation between the expression of GP88 and large tumor size, tumor grade, and lymph node metastasis (LNM). While a negative statistical correlation was noticed between the expression of GP88 and ER, PR, and HER2/neu status.
Discussion: The results of the quantitative immunostaining density of GP88 glycoprotein antibody revealed it to be a valuable predictive and therapeutic marker of GP88 in human IDC patients.

Keywords

HER2/neu; GP88; Clinical pathological parameter; Invasive ductal carcinoma; Immunohistochemical staining; Integrated optical density

References

1. Khan HM, Saxena A, Vera V, Abdool-Ghany F, Gabbidon K, Perea N, et al. Black Hispanic and Black non-Hispanic breast cancer survival data analysis with half-normal model application. Asian Pac J Cancer Prev. 2014;15(21):9453-8. doi: 10.7314/apjcp.2014.15.21.9453.
2. Byers T, Wender RC, Jemal A, Baskies AM, Ward EE, Brawley OW. The American Cancer Society challenge goal to reduce US cancer mortality by 50% between 1990 and 2015: Results and reflections. CA Cancer J Clin. 2016;66(5):359-69. doi: 10.3322/caac.21348.
3. Lehner J, Stötzer OJ, Fersching D, Nagel D, Holdenrieder S. Circulating plasma DNA and DNA integrity in breast cancer patients undergoing neoadjuvant chemotherapy. Clin Chim Acta. 2013;425:206-11. doi: 10.1016/j.cca.2013.07.027.
4. Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. 2011;378(9801):1461-84. doi: 10.1016/S0140-6736(11)61351-2.
5. Smith RA, Manassaram-Baptiste D, Brooks D, Cokkinides V, Doroshenk M, Saslow D, et al. Cancer screening in the United States, 2014: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2014;64(1):30-51. doi: 10.3322/caac.21212.
6. Pandya S, Moore RG. Breast development and anatomy. Clin Obstet Gynecol. 2011;54(1):91-5. doi: 10.1097/GRF.0b013e318207ffe9.
7. Cameron MD, Schmidt EE, Kerkvliet N, Nadkarni KV, Morris VL, Groom AC, et al. Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res. 2000;60(9):2541-6.
8. Young B, O'Dowd G, Woodford Ph. Wheater's Functional Histology: A Text and Colour Atlas. 6th ed. Elsevier, Churchill Living Stone; 2013.
9. Schwartz AM, Henson DE, Chen D, Rajamarthandan S. Histologic grade remains a prognostic factor for breast cancer regardless of the number of positive lymph nodes and tumor size: a study of 161 708 cases of breast cancer from the SEER Program. Arch Pathol Lab Med. 2014;138(8):1048-52. doi: 10.5858/arpa.2013-0435-OA.
10. Harris JR, Lippman ME, Morrow M, Osborne CK. Diseases of the Breast. 5th ed. Lippincott Williams & Wilkins; 2014.
11. Liu CJ, Bosch X. Progranulin: a growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther. 2012;133(1):124-32. doi: 10.1016/j.pharmthera.2011.10.003.
12. Bateman A, Bennett HP. The granulin gene family: from cancer to dementia. Bioessays. 2009;31(11):1245-54. doi: 10.1002/bies.200900086.
13. Halper J. Growth factors as active participants in carcinogenesis: a perspective. Vet Pathol. 2010;47(1):77-97. doi: 10.1177/0300985809352981.
14. Yin F, Banerjee R, Thomas B, Zhou P, Qian L, Jia T, et al. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med. 2010;207(1):117-28. doi: 10.1084/jem.20091568.
15. Feng JQ, Guo FJ, Jiang BC, Zhang Y, Frenkel S, Wang DW, et al. Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. FASEB J. 2010;24(6):1879-92. doi: 10.1096/fj.09-144659.
16. Lu Y, Zheng L, Zhang W, Feng T, Liu J, Wang X, et al. Growth factor progranulin contributes to cervical cancer cell proliferation and transformation in vivo and in vitro. Gynecol Oncol. 2014;134(2):364-71. doi: 10.1016/j.ygyno.2014.05.025.
17. Arechavaleta-Velasco F, Perez-Juarez CE, Gerton GL, Diaz-Cueto L. Progranulin and its biological effects in cancer. Med Oncol. 2017;34(12):194. doi: 10.1007/s12032-017-1054-7.
18. De Muynck L, Van Damme P. Cellular effects of progranulin in health and disease. J Mol Neurosci. 2011;45(3):549-60. doi: 10.1007/s12031-011-9553-z.
19. Cuevas-Antonio R, Cancino C, Arechavaleta-Velasco F, Andrade A, Barron L, Estrada I, et al. Expression of progranulin (Acrogranin/PCDGF/Granulin-Epithelin Precursor) in benign and malignant ovarian tumors and activation of MAPK signaling in ovarian cancer cell line. Cancer Invest. 2010;28(5):452-8. doi: 10.3109/07357900903346455.
20. Toh H, Cao M, Daniels E, Bateman A. Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model. PLoS One. 2013;8(5):e64989. doi: 10.1371/journal.pone.0064989.
21. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305(6):569-75. doi: 10.1001/jama.2011.90.
22. Orucevic A, Chen J, McLoughlin JM, Heidel RE, Panella T, Bell J. Is the TNM staging system for breast cancer still relevant in the era of biomarkers and emerging personalized medicine for breast cancer - an institution's 10-year experience. Breast J. 2015;21(2):147-54. doi: 10.1111/tbj.12367.
23. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-84. doi: 10.1056/NEJMoa052122.
24. Slamon DJ, Romond EH, Perez EA; CME Consultants, Inc. Advances in adjuvant therapy for breast cancer. Clin Adv Hematol Oncol. 2006;4(3 Suppl 7):suppl 1, 4-9; discussion suppl 10; quiz 2 p following suppl 10.
25. Bansal C, Singh US, Misra S, Sharma KL, Tiwari V, Srivastava AN. Comparative evaluation of the modified Scarff-Bloom-Richardson grading system on breast carcinoma aspirates and histopathology. Cytojournal. 2012;9:4. doi: 10.4103/1742-6413.92550.
26. Buchwalow IB, Bocker W. Immunohistochemistry:Basics and Methods. Springer Heidelberg Dordrecht; 2010.
27. Matos LL, Stabenow E, Tavares MR, Ferraz AR, Capelozzi VL, Pinhal MA. Immunohistochemistry quantification by a digital computer-assisted method compared to semiquantitative analysis. Clinics (Sao Paulo). 2006;61(5):417-24. doi: 10.1590/s1807-59322006000500008.
28. Edelman MJ, Feliciano J, Yue B, Bejarano P, Ioffe O, Reisman D, et al. GP88 (progranulin): a novel tissue and circulating biomarker for non-small cell lung carcinoma. Hum Pathol. 2014;45(9):1893-9. doi: 10.1016/j.humpath.2014.05.011.
29. Tkaczuk KR, Yue B, Zhan M, Tait N, Yarlagadda L, Dai H, Serrero G. Increased Circulating Level of the Survival Factor GP88 (Progranulin) in the Serum of Breast Cancer Patients When Compared to Healthy Subjects. Breast Cancer (Auckl). 2011;5:155-62. doi: 10.4137/BCBCR.S7224.
30. Serrero G, Hawkins DM, Yue B, Ioffe O, Bejarano P, Phillips JT, et al. Progranulin (GP88) tumor tissue expression is associated with increased risk of recurrence in breast cancer patients diagnosed with estrogen receptor positive invasive ductal carcinoma. Breast Cancer Res. 2012;14(1):R26. doi: 10.1186/bcr3111.
31. Han JJ, Yu M, Houston N, Steinberg SM, Kohn EC. Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers. Gynecol Oncol. 2011;120(1):5-10. doi: 10.1016/j.ygyno.2010.09.006.
32. Serrero G, Ioffe OB. Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium. Hum Pathol. 2003;34(11):1148-54. doi: 10.1016/s0046-8177(03)00425-8.
33. Zhang Y, Bateman A. The Glycoprotein Growth Factor Progranulin Promotes Carcinogenesis and has Potential Value in Anti-cancer Therapy. J Carcinogene Mutagene. 2011;S2. doi: 10.4172/2157-2518.S2-001.
34. He Z, Ismail A, Kriazhev L, Sadvakassova G, Bateman A. Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. Cancer Res. 2002;62(19):5590-6.
35. Tangkeangsirisin W, Serrero G. PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF
expression in breast cancer cells. Carcinogenesis. 2004;25(9):1587-92. doi: 10.1093/carcin/bgh171.
36. Li LQ, Min LS, Jiang Q, Ping JL, Li J, Dai LC. Progranulin expression in breast cancer with different intrinsic subtypes. Pathol Res Pract. 2012;208(4):210-6. doi: 10.1016/j.prp.2012.02.001.
37. Tkaczuk KHR, Hawkins D, Yue B, Hicks D, Tait N, Serrero G. Association of Serum Progranulin Levels With Disease Progression, Therapy Response and Survival in Patients With Metastatic Breast Cancer. Clin Breast Cancer. 2020;20(3):220-7. doi: 10.1016/j.clbc.2019.11.010.
38. Donald CD, Laddu A, Chandham P, Lim SD, Cohen C, Amin M, et al. Expression of progranulin and the epithelin/granulin precursor acrogranin correlates with neoplastic state in renal epithelium. Anticancer Res. 2001;21(6A):3739-42.
39. Monami G, Emiliozzi V, Bitto A, Lovat F, Xu SQ, Goldoni S, et al. Proepithelin regulates prostate cancer cell biology by promoting cell growth, migration, and anchorage-independent growth. Am J Pathol. 2009;174(3):1037-47. doi: 10.2353/ajpath.2009.080735.
40. Ho JC, Ip YC, Cheung ST, Lee YT, Chan KF, Wong SY, Fan ST. Granulin-epithelin precursor as a therapeutic target for hepatocellular carcinoma. Hepatology. 2008;47(5):1524-32. doi: 10.1002/hep.22191.
41. Chen XY, Li JS, Liang QP, He DZ, Zhao J. Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance. Chin Med J (Engl). 2008;121(10):881-6.
42. Koo DH, Park CY, Lee ES, Ro J, Oh SW. Progranulin as a prognostic biomarker for breast cancer recurrence in patients who had hormone receptor-positive tumors: a cohort study. PLoS One. 2012;7(6):e39880. doi: 10.1371/journal.pone.0039880.
43. Demorrow S. Progranulin: a novel regulator of gastrointestinal cancer progression. Transl Gastrointest Cancer. 2013;2(3):145-51. doi: 10.3978/j.issn.2224-4778.2013.02.02.
44. Shi L, Song HP, Liu CP, Huang T. [Effect of PC-cell derived growth factor shRNA on estrogen dependent of estrogen receptor negative breast cancer cell lines]. Zhonghua Wai Ke Za Zhi. 2007;45(7):483-6.
45. Lu R, Serrero G. Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468. Proc Natl Acad Sci U S A. 2000;97(8):3993-8. doi: 10.1073/pnas.97.8.3993.
46. Lilling G, Hacohen H, Nordenberg J, Livnat T, Rotter V, Sidi Y. Differential sensitivity of MCF-7 and LCC2 cells, to multiple growth inhibitory agents: possible relation to high bcl-2/bax ratio? Cancer Lett. 2000;161(1):27-34. doi: 10.1016/s0304-3835(00)00579-6.
47. Kim WE, Serrero G. PC cell-derived growth factor stimulates proliferation and confers Trastuzumab resistance to Her-2-overexpressing breast cancer cells. Clin Cancer Res. 2006;12(14 Pt 1):4192-9. doi: 10.1158/1078-0432.CCR-05-2663.
48. Donnelly SM, Paplomata E, Peake BM, Sanabria E, Chen Z, Nahta R. P38 MAPK contributes to resistance and invasiveness of HER2- overexpressing breast cancer. Curr Med Chem. 2014;21(4):501-10. doi: 10.2174/0929867320666131119155023.
49. Kim JH, Do IG, Kim K, Sohn JH, Kim HJ, Jeon WK, et al. Progranulin as a predictive factor of response to chemotherapy in advanced biliary tract carcinoma. Cancer Chemother Pharmacol. 2016;78(5):1085-1092. doi: 10.1007/s00280-016-3170-z.


Submitted date:
12/18/2020

Reviewed date:
12/30/2020

Accepted date:
01/04/2021

Publication date:
01/07/2021

5ff6568b0e8825f479959f62 iberoamericanjm Articles
Links & Downloads

Iberoam J Med

Share this page
Page Sections