nach oben

Erschienen in:

28.07.2017 | Preclinical study

Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast

verfasst von: Fanfan Meng, Bingbing Liu, Gan Xie, Yawen Song, Xia Zheng, Xiaolong Qian, Shuai Li, Hongqin Jia, Xinmin Zhang, Lanjing Zhang, Yi-ling Yang, Li Fu

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome 8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied.

Methods

Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC-NST, and 56 ILC samples using immunohistochemical analysis.

Results

PSCA gene amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC-NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9% (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples, respectively. The concordant rate of the immunohistochemistry and FISH data was 85.2%. PSCA gene amplification highly correlated with its protein overexpression (rs = 0.687, P < 0.001), suggesting that gene amplification is an important mechanism involved in PSCA overexpression. Our univariate analysis showed that the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS) compared to PSCA-negative IMPC patients (P = 0.003). Our multivariate analysis confirmed the worse DFS in PSCA-positive IMPC patients (P = 0.022).

Conclusions

Our results indicate that PSCA may be an attractive target in the 8q24 amplicon and that it may serve as a molecular marker of metastasis and recurrence in IMPC. The differential expression of PSCA may be associated with cell adhesion. Detection of PSCA protein and gene amplification may help manage and predict the prognosis of IMPC patients.

Lakhani S, Schnitt S et al (2012) WHO classification of tumours of the breast, 4th edn. IARC Press, Lyon

Zekioglu O, Erhan Y, Ciris M, Bayramoglu H, Ozdemir N (2004) Invasive micropapillary carcinoma of the breast: high incidence of lymph node metastasis with extranodal extension and its immunohistochemical profile compared with invasive ductal carcinoma. Histopathology 44(1):18–23CrossRefPubMed

Chen L, Fan Y, Lang RG, Guo XJ, Sun YL, Cui LF, Liu FF, Wei J, Zhang XM, Fu L (2008) Breast carcinoma with micropapillary features: clinicopathologic study and long-term follow-up of 100 cases. Int J Surg Pathol 16(2):155–163. doi:10.1177/1066896907307047 CrossRefPubMed

Yang YL, Liu BB, Zhang X, Fu L (2016) Invasive micropapillary carcinoma of the breast: an update. Arch Pathol Lab Med 140(8):799–805. doi:10.5858/arpa.2016-0040-RA CrossRefPubMed

Guo X, Fan Y, Lang R, Gu F, Chen L, Cui L, Pringle GA, Zhang X, Fu L (2008) Tumor infiltrating lymphocytes differ in invasive micropapillary carcinoma and medullary carcinoma of breast. Mod Pathol 21(9):1101–1107. doi:10.1038/modpathol.2008.72 CrossRefPubMed

Marchiò C, Iravani M, Natrajan R, Lambros MB, Savage K, Tamber N, Fenwick K, Mackay A, Senetta R, Palma SD, Schmitt FC, Bussolati G, Ellis IO, Ashworth A, Sapino A, Reis-Filho JS (2008) Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast. J Pathol 215(4):398–410. doi:10.1002/path.2368 CrossRefPubMed

Gunther K, Merkelbach-Bruse S, Amo-Takyi BK, Handt S, Schroder W, Tietze L (2001) Differences in genetic alterations between primary lobular and ductal breast cancers detected by comparative genomic hybridization. J Pathol 193(1):40–47. doi:10.1002/1096-9896(2000)9999:9999<:AID-PATH745>3.0.CO;2-N CrossRefPubMed

Reiter RE, Gu Z, Watabe T, Thomas G, Szigeti K, Davis E, Wahl M, Nisitani S, Yamashiro J, Le Beau MM, Loda M, Witte ON (1998) Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci USA 95(4):1735–1740CrossRefPubMedPubMedCentral

Reiter RE, Sato I, Thomas G, Qian J, Gu Z, Watabe T, Loda M, Jenkins RB (2000) Coamplification of prostate stem cell antigen (PSCA) and MYC in locally advanced prostate cancer. Genes Chromosom Cancer 27(1):95–103CrossRefPubMed

10.

Hao JY, Yang YL, Li S, Qian XL, Liu FF, Fu L (2011) PSCA expression in invasive micropapillary carcinoma of breast. Chin J Pathol 40(6):382–386

11.

Catenacci DV, Ang A, Liao WL, Shen J, O’Day E, Loberg RD, Cecchi F, Hembrough T, Ruzzo A, Graziano F (2016) MET tyrosine kinase receptor expression and amplification as prognostic biomarkers of survival in gastroesophageal adenocarcinoma. Cancer. doi:10.1002/cncr.30437 PubMedCentral

12.

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, Hanna W, Jenkins RB, Mangu PB, Paik S, Perez EA, Press MF, Spears PA, Vance GH, Viale G, Hayes DF, American Society of Clinical O, College of American P (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31(31):3997–4013. doi:10.1200/JCO.2013.50.9984 CrossRefPubMed

13.

Pauletti G, Godolphin W, Press MF, Slamon DJ (1996) Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene 13(1):63–72PubMed

14.

Konecny GE, Thomssen C, Luck HJ, Untch M, Wang HJ, Kuhn W, Eidtmann H, du Bois A, Olbricht S, Steinfeld D, Mobus V, von Minckwitz G, Dandekar S, Ramos L, Pauletti G, Pegram MD, Janicke F, Slamon DJ (2004) Her-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer. J Natl Cancer Inst 96(15):1141–1151. doi:10.1093/jnci/djh198 CrossRefPubMed

15.

Gu Z, Thomas G, Yamashiro J, Shintaku IP, Dorey F, Raitano A, Witte ON, Said JW, Loda M, Reiter RE (2000) Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer. Oncogene 19(10):1288–1296. doi:10.1038/sj.onc.1203426 CrossRefPubMed

16.

Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical O, College of American P (2007) 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 25(1):118–145. doi:10.1200/JCO.2006.09.2775 CrossRefPubMed

17.

Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, Hicks DG, Lester S, Love R, Mangu PB, McShane L, Miller K, Osborne CK, Paik S, Perlmutter J, Rhodes A, Sasano H, Schwartz JN, Sweep FC, Taube S, Torlakovic EE, Valenstein P, Viale G, Visscher D, Wheeler T, Williams RB, Wittliff JL, Wolff AC (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med 134(6):907–922. doi:10.1043/1543-2165-134.6.907 PubMedPubMedCentral

18.

Gong Y, Sun X, Huo L, Wiley EL, Rao MS (2005) Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast. Histopathology 46(1):24–30. doi:10.1111/j.1365-2559.2004.01981.x CrossRefPubMed

19.

Marchio C, Iravani M, Natrajan R, Lambros MB, Geyer FC, Savage K, Parry S, Tamber N, Fenwick K, Mackay A, Schmitt FC, Bussolati G, Ellis I, Ashworth A, Sapino A, Reis-Filho JS (2009) Mixed micropapillary-ductal carcinomas of the breast: a genomic and immunohistochemical analysis of morphologically distinct components. J Pathol 218(3):301–315. doi:10.1002/path.2572 CrossRefPubMed

20.

Hicks J, Krasnitz A, Lakshmi B, Navin NE, Riggs M, Leibu E, Esposito D, Alexander J, Troge J, Grubor V, Yoon S, Wigler M, Ye K, Borresen-Dale AL, Naume B, Schlicting E, Norton L, Hagerstrom T, Skoog L, Auer G, Maner S, Lundin P, Zetterberg A (2006) Novel patterns of genome rearrangement and their association with survival in breast cancer. Genome Res 16(12):1465–1479. doi:10.1101/gr.5460106 CrossRefPubMedPubMedCentral

21.

Kim JH, Dhanasekaran SM, Mehra R, Tomlins SA, Gu W, Yu J, Kumar-Sinha C, Cao X, Dash A, Wang L, Ghosh D, Shedden K, Montie JE, Rubin MA, Pienta KJ, Shah RB, Chinnaiyan AM (2007) Integrative analysis of genomic aberrations associated with prostate cancer progression. Can Res 67(17):8229–8239. doi:10.1158/0008-5472.CAN-07-1297 CrossRef

22.

Isola JJ, Kallioniemi OP, Chu LW, Fuqua SA, Hilsenbeck SG, Osborne CK, Waldman FM (1995) Genetic aberrations detected by comparative genomic hybridization predict outcome in node-negative breast cancer. Am J Pathol 147(4):905–911PubMedPubMedCentral

23.

Tirkkonen M, Tanner M, Karhu R, Kallioniemi A, Isola J, Kallioniemi OP (1998) Molecular cytogenetics of primary breast cancer by CGH. Genes Chromosom Cancer 21(3):177–184CrossRefPubMed

24.

Hermsen MA, Baak JP, Meijer GA, Weiss JM, Walboomers JW, Snijders PJ, van Diest PJ (1998) Genetic analysis of 53 lymph node-negative breast carcinomas by CGH and relation to clinical, pathological, morphometric, and DNA cytometric prognostic factors. J Pathol 186(4):356–362. doi:10.1002/(SICI)1096-9896(199812)186:4<356:AID-PATH196>3.0.CO;2-Z CrossRefPubMed

25.

Ambatipudi S, Gerstung M, Pandey M, Samant T, Patil A, Kane S, Desai RS, Schaffer AA, Beerenwinkel N, Mahimkar MB (2012) Genome-wide expression and copy number analysis identifies driver genes in gingivobuccal cancers. Genes Chromosom Cancer 51(2):161–173. doi:10.1002/gcc.20940 CrossRefPubMed

26.

Adler AS, Lin M, Horlings H, Nuyten DS, van de Vijver MJ, Chang HY (2006) Genetic regulators of large-scale transcriptional signatures in cancer. Nat Genet 38(4):421–430. doi:10.1038/ng1752 CrossRefPubMedPubMedCentral

27.

Lightfoot HM Jr, Lark A, Livasy CA, Moore DT, Cowan D, Dressler L, Craven RJ, Cance WG (2004) Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis. Breast Cancer Res Treat 88(2):109–116. doi:10.1007/s10549-004-1022-8 CrossRefPubMed

28.

Lam JS, Yamashiro J, Shintaku IP, Vessella RL, Jenkins RB, Horvath S, Said JW, Reiter RE (2005) Prostate stem cell antigen is overexpressed in prostate cancer metastases. Clin Cancer Res 11(7):2591–2596. doi:10.1158/1078-0432.CCR-04-1842 CrossRefPubMed

29.

Liang JW, Shi ZZ, Shen TY, Che X, Wang Z, Shi SS, Xu X, Cai Y, Zhao P, Wang CF, Zhou ZX, Wang MR (2014) Identification of genomic alterations in pancreatic cancer using array-based comparative genomic hybridization. PLoS ONE 9(12):e114616. doi:10.1371/journal.pone.0114616 CrossRefPubMedPubMedCentral

30.

Wang L, Sang Y, Tang J, Zhang RH, Luo D, Chen M, Deng WG, Kang T (2015) Down-regulation of prostate stem cell antigen (PSCA) by Slug promotes metastasis in nasopharyngeal carcinoma. J Pathol 237(4):411–422. doi:10.1002/path.4582 CrossRefPubMed

31.

Bahrenberg G, Brauers A, Joost HG, Jakse G (2001) PSCA expression is regulated by phorbol ester and cell adhesion in the bladder carcinoma cell line RT112. Cancer Lett 168(1):37–43CrossRefPubMed

32.

Kang R, Zhao S, Liu L, Li F, Li E, Luo L, Xu L, Wan S, Zhao Z (2016) Knockdown of PSCA induces EMT and decreases metastatic potentials of the human prostate cancer DU145 cells. Cancer Cell Int 16:20. doi:10.1186/s12935-016-0295-4 CrossRefPubMedPubMedCentral

33.

Fu L, Ikuo M, Fu XY, Liu TH, Shinichi T (2004) Relationship between biologic behavior and morphologic features of invasive micropapillary carcinoma of the breast. Chin J Pathol 33(1):21–25

34.

Martin TA, Jiang WG (2014) Evaluation of the expression of stem cell markers in human breast cancer reveals a correlation with clinical progression and metastatic disease in ductal carcinoma. Oncol Rep 31(1):262–272. doi:10.3892/or.2013.2813 CrossRefPubMed

35.

Matera L (2010) The choice of the antigen in the dendritic cell-based vaccine therapy for prostate cancer. Cancer Treat Rev 36(2):131–141. doi:10.1016/j.ctrv.2009.11.002 CrossRefPubMed

36.

Olafsen T, Gu Z, Sherman MA, Leyton JV, Witkosky ME, Shively JE, Raubitschek AA, Morrison SL, Wu AM, Reiter RE (2007) Targeting, imaging, and therapy using a humanized antiprostate stem cell antigen (PSCA) antibody. J Immunother 30(4):396–405. doi:10.1097/CJI.0b013e318031b53b CrossRefPubMed

Titel: Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast
verfasst von: Fanfan Meng
Bingbing Liu
Gan Xie
Yawen Song
Xia Zheng
Xiaolong Qian
Shuai Li
Hongqin Jia
Xinmin Zhang
Lanjing Zhang
Yi-ling Yang
Li Fu
Publikationsdatum: 28.07.2017
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-017-4407-1

Springer Medizin

Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast