{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:49:51Z","timestamp":1782211791646,"version":"3.54.5"},"reference-count":52,"publisher":"Termedia Sp. z.o.o.","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pol J Pathol"],"abstract":"<jats:p>Breast cancer is the\u00a0most leading cause of\u00a0cancer death in females worldwide. Identification of\u00a0novel biomarkers for prognosis is required. Imunohistochemical evaluation of\u00a0CIP2A and ROCK-1 expressions in 126 breast tissue specimens stratified as 21 ductal hyperplasias, 17 duct carcinoma in situ (DCIS) and 88 invasive carcinomas (56 invasive ductal carcinomas NST, 32 invasive lobular carcinomas) was studied. High CIP2A expression was detected in 48.9% of\u00a0invasive carcinomas. CIP2A overexpression was significantly related to Nottingham prognostic index (NPI) (p\u00a0=\u00a00.011), stage (p\u00a0=\u00a00.01), ER negativity (p\u00a0=\u00a00.031), PR negativity (p\u00a0=\u00a00.048), and HER-2 positivity (p\u00a0=\u00a00.02). CIP2A was significantly overexpressed in triple-negative breast cancer (TNBC) (p\u00a0=\u00a00.004). ROCK-1 expression was detected in 54.5% of\u00a0invasive carcinomas. Statistically significant associations were observed between ROCK-1 expression and NPI (p\u00a0=\u00a00.032), stage (p\u00a0=\u00a00.002), ER negativity (p\u00a0=\u00a00.012), PR negativity (p\u00a0=\u00a00.023), HER-2 positivity (p\u00a0=\u00a00.016), and TNBC subtype (p\u00a0=\u00a00.033). A\u00a0positive association between CIP2A and ROCK-1 expressions (p\u00a0&lt;\u00a00.0001) was documented. There was a\u00a0significant association between shorter overall survival and high CIP2A and positive ROCK-1 expressions (p\u00a0&lt;\u00a00.0001) and (p\u00a0&lt;\u00a00.0001). CIP2A and ROCK-1 expressions could be used as markers for the\u00a0poor prognosis of\u00a0breast cancer.<\/jats:p>","DOI":"10.5114\/pjp.2020.97016","type":"journal-article","created":{"date-parts":[[2020,7,26]],"date-time":"2020-07-26T17:10:58Z","timestamp":1595783458000},"page":"87-98","source":"Crossref","is-referenced-by-count":11,"title":["Assessment of CIP2A and ROCK-I expression and their prognostic value in breast cancer"],"prefix":"10.5114","volume":"71","author":[{"given":"Nisreen Abdel","family":"Tawab Osman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal A.","family":"Khalaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaymaa A.S.","family":"Ibraheem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3061","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"ref-1696132","doi-asserted-by":"crossref","unstructured":"Bray F, Ferlay J, Soerjomataram I, et al. Global Cancer Statistics 2018: GLOBOCAN Estimates of\u00a0Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Cancer J Clin 2018; 68: 394-424.","DOI":"10.3322\/caac.21492"},{"key":"ref-1696133","doi-asserted-by":"crossref","unstructured":"Ibrahim AS,\u00a0Khaled HM, Mikhail NH, et al. Cancer Incidence in Egypt: Results of\u00a0the\u00a0National Population-Based Cancer Registry Program. J Cancer Epidemiol 2014; 2014: ID\u00a0437971.","DOI":"10.1155\/2014\/437971"},{"key":"ref-1696134","doi-asserted-by":"crossref","unstructured":"Greenlee RT, Mukesh BN, Onitilo AA, Engel J. Breast Cancer Subtypes Based on ER\/PR and Her2 Expression: Comparison of\u00a0Clinicopathologic Features and Survival. Clin Med Res 2009; 7: 4-13.","DOI":"10.3121\/cmr.2008.825"},{"key":"ref-1696135","doi-asserted-by":"crossref","unstructured":"Singletary SE, Allred C, Ashley P,  et al. Staging system for breast cancer: revisions for the\u00a06th edition of\u00a0the\u00a0AJCC Cancer Staging Manual. Surg Clin North Am 2003; 83: 803-819.","DOI":"10.1016\/S0039-6109(03)00034-3"},{"key":"ref-1696136","doi-asserted-by":"crossref","unstructured":"Bast RC, Ravdin P, Hayes DF, et al.  2000 Update of\u00a0recommendations for the\u00a0use of\u00a0tumor markers in breast and colorectal cancer: clinical practice guidelines of\u00a0the\u00a0American society of\u00a0clinical oncology. J Clin Oncol 2001; 19: 1865-1878.","DOI":"10.1200\/JCO.2001.19.6.1865"},{"key":"ref-1696137","doi-asserted-by":"crossref","unstructured":"Morin PJ. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 2005; 65: 9603-9606.","DOI":"10.1158\/0008-5472.CAN-05-2782"},{"key":"ref-1696138","doi-asserted-by":"crossref","unstructured":"Marotti JD, de Abreu FB, Wells WA, Tsongalis GJ. Triple-Negative Breast Cancer, Next-Generation Sequencing for Target Identification. Am J Pathol 2017; 187:  2133-2138.","DOI":"10.1016\/j.ajpath.2017.05.018"},{"key":"ref-1696139","doi-asserted-by":"crossref","unstructured":"Kaplan HG, Malmgren JA,  Atwood M. T1N0 triple negative breast cancer: risk of\u00a0recurrence and adjuvant chemotherapy. Breast J 2009; 15: 454-460.","DOI":"10.1111\/j.1524-4741.2009.00789.x"},{"key":"ref-1696140","doi-asserted-by":"crossref","unstructured":"Westermarck J, Hahn WC. Multiple pathways regulated by the\u00a0tumor suppressor PP2A in transformation. Trends Mol Med 2008; 14: 152-160.","DOI":"10.1016\/j.molmed.2008.02.001"},{"key":"ref-1696141","doi-asserted-by":"crossref","unstructured":"Khanna A, Pimanda JE,  Westermarck J. Cancerous Inhibitor of\u00a0Protein Phosphatase 2A, an\u00a0Emerging Human Oncoprotein and a\u00a0Potential Cancer Therapy Target. Cancer Res 2013; 73: 6548-6553.","DOI":"10.1158\/0008-5472.CAN-13-1994"},{"key":"ref-1696142","doi-asserted-by":"crossref","unstructured":"Junttila\u00a0MR, Puustinen\u00a0P, Niemel\u00e4\u00a0M,\u00a0et\u00a0al. CIP2A inhibits PP2A in human malignancies. Cell 2007;\u00a0130: 51-62.","DOI":"10.1016\/j.cell.2007.04.044"},{"key":"ref-1696143","doi-asserted-by":"crossref","unstructured":"Arnold HK, Sears RC. Protein phosphatase 2A regulatory subunit B56alpha associates with c-myc and negatively regulates c-myc accumulation. Mol Cell Biol 2006; 26: 2832-2844.","DOI":"10.1128\/MCB.26.7.2832-2844.2006"},{"key":"ref-1696144","doi-asserted-by":"crossref","unstructured":"Lucas CM, Harris RJ, Giannoudis A, et al. Cancerous inhibitor of\u00a0PP2A (CIP2A) at diagnosis of\u00a0chronic myeloidleukemia is a\u00a0critical determinant of\u00a0disease progression. Blood 2011; 117: 6660-6668.","DOI":"10.1182\/blood-2010-08-304477"},{"key":"ref-1696145","doi-asserted-by":"crossref","unstructured":"Pang X, Fu X, Chen S, et al. Overexpression of\u00a0CIP2A promotes bladder cancer progression by regulating EMT. Clin Transl Oncol 2016; 18: 289-295.","DOI":"10.1007\/s12094-015-1366-z"},{"key":"ref-1696146","doi-asserted-by":"crossref","unstructured":"Cha G, Xu J, Xu X, et al. High expression of\u00a0CIP2A protein is associated with tumor aggressiveness in stage I-III NSCLC and correlates with poor prognosis. Onco Targets Ther  2017; 10: 5907-5914.","DOI":"10.2147\/OTT.S148250"},{"key":"ref-1696147","doi-asserted-by":"crossref","unstructured":"Liu X, Cao W, Qin S, et al. Overexpression of\u00a0CIP2A is associated with poorprognosis in multiplemyeloma. Signal Transduct Target Ther  2017; 2: 17013.","DOI":"10.1038\/sigtrans.2017.13"},{"key":"ref-1696148","doi-asserted-by":"crossref","unstructured":"Yu N, Zhang T, Zhao D, et al. CIP2A is overexpressed in human endometrioid adenocarcinoma and regulates cell proliferation, invasion and apoptosis. Pathol Res Pract 2018; 214: 233-239.","DOI":"10.1016\/j.prp.2017.11.011"},{"key":"ref-1696149","doi-asserted-by":"crossref","unstructured":"Baldacchino S, Wastall LM, Saliba C, et al. CIP2A expression predicts recurrences of\u00a0tamoxifen-treated breast cancer. Tumour Biol 2017; 39: 1010428317722064.","DOI":"10.1177\/1010428317722064"},{"key":"ref-1696150","doi-asserted-by":"crossref","unstructured":"Singh P, Carraher C, Schwarzbauer JE. Assembly of\u00a0fibronectin extracellular matrix. Annu Rev Cell Dev Biol  2010; 10: 397-419.","DOI":"10.1146\/annurev-cellbio-100109-104020"},{"key":"ref-1696151","doi-asserted-by":"crossref","unstructured":"Skarp KP, Vartiainen MK. Actin on DNA-An ancient and dynamic relationship. Cytoskeleton 2010; 67: 487-495.","DOI":"10.1002\/cm.20464"},{"key":"ref-1696152","doi-asserted-by":"crossref","unstructured":"Matsui T, Amano M, Yamamoto T, et al. Rho-associated kinase, a\u00a0novel serine\/threonine kinase, as a\u00a0putative target for small GTP binding protein Rho. EMBO J 1996; 15: 2208-2216.","DOI":"10.1002\/j.1460-2075.1996.tb00574.x"},{"key":"ref-1696153","doi-asserted-by":"crossref","unstructured":"Julian L, Olson MF. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases 2014; 5: e29846.","DOI":"10.4161\/sgtp.29846"},{"key":"ref-1696154","doi-asserted-by":"crossref","unstructured":"Blumenstein L, Ahmadian MR. Models of\u00a0the\u00a0cooperative mechanism for Rho effector recognition: implications for RhoA-mediated effector activation. J Biol Chem 2004; 279: 53419-53426.","DOI":"10.1074\/jbc.M409551200"},{"key":"ref-1696155","doi-asserted-by":"crossref","unstructured":"Benitah SA, Valeron PF, van Aelst L, et al. Rho GTPases in human cancer: an\u00a0unresolved link to upstream and downstream transcriptional regulation. Biochim Biophys Acta 2004; 1705: 121-132.","DOI":"10.1016\/j.bbcan.2004.10.002"},{"key":"ref-1696156","unstructured":"Kamai T, Tsujii T, Arai K, et al. Significant association of\u00a0Rho\/ROCK pathway with invasion and metastasis of\u00a0bladder cancer. Clin Cancer Res 2003; 9: 2632-2641."},{"key":"ref-1696157","doi-asserted-by":"crossref","unstructured":"Abe H, Kamai T, Tsujii T, et al. Possible role of\u00a0the\u00a0RhoC\/ROCK pathway in progression of\u00a0clear cell renal cell carcinoma. Biomed Res 2008; 29: 155-161.","DOI":"10.2220\/biomedres.29.155"},{"key":"ref-1696158","doi-asserted-by":"crossref","unstructured":"Akagi EM, Lavorato-Rocha AM, Maia B de M, et al. ROCK1 as a\u00a0novel prognostic marker in vulvar cancer. BMC Cancer 2014; 14: 822.","DOI":"10.1186\/1471-2407-14-822"},{"key":"ref-1696159","doi-asserted-by":"crossref","unstructured":"Wu YJ, Tang Y, Li ZF, et al. Expression and significance of\u00a0Rac1, Pak1 and Rock1 in gastric carcinoma. Asia Pac J Clin Oncol 2014; 10: e33-e39.","DOI":"10.1111\/ajco.12052"},{"key":"ref-1696160","doi-asserted-by":"crossref","unstructured":"Xue F, Takahara T, Yata Y, et al. Blockade of\u00a0Rho\/Rho-associated coiled coil-forming kinase signaling can prevent progression of\u00a0hepatocellular carcinoma in matrix metalloproteinase-dependent manner. Hepatol Res 2008; 38: 810-817.","DOI":"10.1111\/j.1872-034X.2008.00333.x"},{"key":"ref-1696161","doi-asserted-by":"crossref","unstructured":"Jeong KJ, Park SY, Cho KH, et al. The\u00a0Rho\/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion. Oncogene 2012; 31: 4279-4289.","DOI":"10.1038\/onc.2011.595"},{"key":"ref-1696162","doi-asserted-by":"crossref","unstructured":"Liu S, Goldstein RH, Scepansky EM, Rosenblatt M. Inhibition of\u00a0rho- associated kinase signaling prevents breastcancer metastasis to human bone. Cancer Res 2009; 69: 8742-8751.","DOI":"10.1158\/0008-5472.CAN-09-1541"},{"key":"ref-1696163","doi-asserted-by":"crossref","unstructured":"Patel RA, Forinash KD, Pireddu R, et al. RKI- 1447 is a\u00a0potent inhibitor of\u00a0the\u00a0Rho associatedROCK kinases with anti-invasive and antitumoractivities in breast cancer. Cancer Res 2012; 72: 5025-5034.","DOI":"10.1158\/0008-5472.CAN-12-0954"},{"key":"ref-1696164","doi-asserted-by":"crossref","unstructured":"Bottinoa J, Gelaleti GB, Maschioa LB, et al. Immuno expression of\u00a0ROCK-1 and MMP-9 as prognostic markers in breast cancer. Acta Histochemica 2014; 116: 1367-1373.","DOI":"10.1016\/j.acthis.2014.08.009"},{"key":"ref-1696165","doi-asserted-by":"crossref","unstructured":"Dong QZ, Wang Y, Dong XJ, et al. CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Ann Surg Oncol 2011; 18: 857-865.","DOI":"10.1245\/s10434-010-1313-8"},{"key":"ref-1696166","doi-asserted-by":"crossref","unstructured":"Wang JX, Zhou YN, Zou SJ, et al. Correlations of\u00a0P21 activated kinase 1 expression to clinicopathological features of\u00a0gastric carcinoma and patients prognosis. Chin J Cancer 2010; 29: 649-654.","DOI":"10.5732\/cjc.009.10709"},{"key":"ref-1696167","doi-asserted-by":"crossref","unstructured":"C\u00f4me C, Laine A, Chanrion M, et al. CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res 2009; 15: 5092-5100.","DOI":"10.1158\/1078-0432.CCR-08-3283"},{"key":"ref-1696168","doi-asserted-by":"crossref","unstructured":"Niemel\u00e4 M, Kauko O, Sihto H, et al. CIP2A signature reveals the\u00a0MYC dependency of\u00a0CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes. Oncogene 2012; 31: 4266-4278.","DOI":"10.1038\/onc.2011.599"},{"key":"ref-1696169","doi-asserted-by":"crossref","unstructured":"Yu G, Liu G, Dong J, Jin Y. Clinical implications of\u00a0CIP2A protein expression in breast cancer. Med Oncol 2013; 30: 524.","DOI":"10.1007\/s12032-013-0524-9"},{"key":"ref-1696170","doi-asserted-by":"crossref","unstructured":"Liu H, Qiu H, Song Y, et al. Cip2a promotes cell cycle progression in triple-negative breast cancer cells by regulating the\u00a0expression and nuclear  export of\u00a0p27Kip1. Oncogene  2017; 36: 1952-1964.","DOI":"10.1038\/onc.2016.355"},{"key":"ref-1696171","doi-asserted-by":"crossref","unstructured":"Li S, Feng TT, Guo Y, et al. Expression of\u00a0cancerous inhibitor of\u00a0protein phosphatase 2A in human triple negative breast cancer correlates with tumor survival, invasion and autophagy. Oncol Lett 2016; 12: 5370-5376.","DOI":"10.3892\/ol.2016.5374"},{"key":"ref-1696172","doi-asserted-by":"crossref","unstructured":"Gilkes DM, Xiang L, Lee SJ, et al. Hypoxia-inducible factors mediate coordinated RhoAROCK1expression and signaling in breast cancer cells. Proc Natl Acad Sci U S A\u00a02014; 111: E384-E393.","DOI":"10.1073\/pnas.1321510111"},{"key":"ref-1696173","unstructured":"Lane J, Martin TA, Watkins G, et al. The\u00a0expression and prognostic value of\u00a0ROCK I and ROCK II and their role in human breast cancer. Int J Oncol 2008; 33: 585-593."},{"key":"ref-1696174","doi-asserted-by":"crossref","unstructured":"Liu S, Goldstein RH, Scepansky EM, Rosenblatt M. Inhibition of\u00a0Rho-Associated Kinase Signaling Prevents Breast Cancer Metastasis to Human Bone. Cancer Res 2009; 69: 8742-8751.","DOI":"10.1158\/0008-5472.CAN-09-1541"},{"key":"ref-1696175","doi-asserted-by":"crossref","unstructured":"Borin TF, Arbab AS, Gelaleti GB, et al. Melatonin decreases breast cancer metastasis by modulating ROCK-1 expression. J Pineal Res 2016; 60: 3-15.","DOI":"10.1111\/jpi.12270"},{"key":"ref-1696176","doi-asserted-by":"crossref","unstructured":"Ahmed S, Harb OA, Nawar N. Prognostic Implications of\u00a0Claudin 4 and Rock 1 in Triple Negative Breast Cancer. J  Cancer Treat Res 2017; 5: 95-103.","DOI":"10.11648\/j.jctr.20170506.13"},{"key":"ref-1696177","doi-asserted-by":"crossref","unstructured":"Croft DR, Olson MF. The\u00a0Rho GTPase effector ROCK regulates cyclin A, cyclin D1, and p27Kip1 levels by distinct mechanisms. Mol Cell Biol 2006; 26: 4612-4627.","DOI":"10.1128\/MCB.02061-05"},{"key":"ref-1696178","doi-asserted-by":"crossref","unstructured":"Zhang C, Zhang S, Zhang Z, et al. ROCK has a\u00a0crucial role in regulating prostate tumor growth through interaction with c-Myc. Oncogene 2014; 33: 5582-5591.","DOI":"10.1038\/onc.2013.505"},{"key":"ref-1696179","doi-asserted-by":"crossref","unstructured":"Huang Q, Qin S, Yuan X, et al. Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A. Oncol Rep 2017; 38: 598-606.","DOI":"10.3892\/or.2017.5667"},{"key":"ref-1696180","doi-asserted-by":"crossref","unstructured":"Tseng L, Liu C, Chang K, et al. CIP2A is a\u00a0target of\u00a0bortezomib in human triple negative breast cancer cells. Breast Cancer Res 2012; 14: R68.","DOI":"10.1186\/bcr3175"},{"key":"ref-1696181","doi-asserted-by":"crossref","unstructured":"Wei L, Surma M, Shi S, et al. Novel Insights into the\u00a0Roles of\u00a0Rho Kinase in Cancer. Arch Immunol Ther Exp (Warsz) 2016; 64: 259-278.","DOI":"10.1007\/s00005-015-0382-6"},{"key":"ref-1696182","doi-asserted-by":"crossref","unstructured":"Matsubara M, Bissell MJ. Inhibitors of\u00a0Rho kinase (ROCK) signaling revert the\u00a0malignant phenotype of\u00a0breast cancer cells in 3D context. Oncotarget 2016; 7: 31602-31622.","DOI":"10.18632\/oncotarget.9395"},{"key":"ref-1696183","doi-asserted-by":"crossref","unstructured":"Chang F, Zhang Y,  Mi J, et al. ROCK inhibitor enhances the\u00a0growth and migration of\u00a0BRAF-mutant skin melanoma cells. Cancer Sci 2018; 109: 3428-3437.","DOI":"10.1111\/cas.13786"}],"container-title":["Polish Journal of Pathology"],"original-title":[],"link":[{"URL":"https:\/\/www.polishjournalofpathology.com\/pdf-124823-136753","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.polishjournalofpathology.com\/pdf-124823-136753","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:28:31Z","timestamp":1782210511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.polishjournalofpathology.com\/Assessment-of-CIP2A-and-ROCK-I-expression-and-their-prognostic-value-in-breast-cancer,124823,0,2.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,21]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020]]}},"alternative-id":["124823"],"URL":"https:\/\/doi.org\/10.5114\/pjp.2020.97016","relation":{},"ISSN":["1233-9687","2084-9869"],"issn-type":[{"value":"1233-9687","type":"print"},{"value":"2084-9869","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,21]]}}}