Objective: To investigate the expression and clinical significance of CCN5 protein in breast intraductal hyperplastic lesions and breast cancer. Methods: CCN5 was expressed in 20 cases of normal breast tissue(NBT),110 cases of intraductal hyperplasia of breast including 20 cases of usual ductal hyperplasia(UDH), 30 cases of atypical ductal hyperplasia(ADH), 60 cases of ductal carcinoma in situ(DCIS), and 90 cases of invasive lesions(IL) including 60 cases of invasive ductal carcinoma(IDC) and 30 cases of lymph node metastasis(LNM) by immunohistochemical SP method. The relationship between breast cancer and clinicopathological parameters was analyzed.Results: Expression rates of CCN5 protein were 10.00%(2/20),15.00%(3/20), 73.33%(22/30), 71.67%(43/60), 35.00%(21/60) and 16.67%(5/30) in NBT,UDH, ADH, DCIS, IDC, and LNM respectively, and the differences among them were statistically significant(χ2=56.785, P<0.001). Expression rates of CCN5 protein in NBT, intraductal hyperplastic lesions,and IL were 10.00%(2/20), 61.82%(8/110) and 28.89%(6/90) respectively, and the differences were statistically significant(χ2=31.944, P<0.001). Expression rates of CCN5 protein were significantly different(P<0.05) in IDC with different ER, PR, pathological grade, tumor diameter, vascular tumor thrombus and lymph node metastasis, but were not significantly affected by age or location(P>0.05).Conclusion: With the development of breast ductal epithelial from UDH to LNM, the expression rate of the CCN5 protein gradually decreases, suggesting that the CCN5 expression is related to the occurrence and clinical progress of intraductal proliferative lesions and breast cancer. This result may provide a new theoretical basis for diagnosis, clinical treatment and prognosic evaluation of breast cancer and precancerous lesions. |
[1] 丁华野.乳腺病理诊断病例精选[M].北京:人民卫生出版社,2015:87-133.
[2] 杨举伦.乳腺导管内增生性病变是乳腺癌前驱病变[J].临床与实验病理学杂志,2011(9):919-922.
[3] BARRETO S C,RAY A,AG EDGAR P.Biological characteristics of CCN proteins in tumor development[J].J Buon,2016,21(6):1359-1367.
[4] KLEER G G.Dual roles of CCN proteins in breast cancer progression[J].J Cell Commun Signal,2016,10:217-222.
[5] DAS A,DHAR K,MAITY G,et al.Deficiency of CCN5/WISP-2 drivern program in brast cancer promotes cancer epithelial cells to mesenchymal stem cells and breast cancer growth[J].Sci Rep,2017,7(1):1220-1233.
[6] BANERJEE S K,BANERJEE S.CCN5/WISP-2:a micromanager of breast cancer prgression[J].J Cell Commun Signal,2012,6(2):63-71.
[7] SARKAR S,GHOSH A,BANEJEE S,et al.CCN5/WISP-2 restores ER-α in normal and neoplastic breast cells and sensitizes triple negative breast cancer cells to tamoxifen[J].Oncogenesis,2017,6:e340.
[8] HAQUE I,BANERJEE S,DE A,et al.CCN5/WISP-2 promotes growth arrest of triple-negative breast cancer cells through accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation[J].Oncogene,2015,11(34):3152-3163.
[9] NADIA H,MICHAEL G.Breast cancer[J].Seminar,2017,389:1134-1150.
[10] 张思浩,崔童星,王刚平,等.乳腺癌前病变研究的最新进展[J].临床普外科电子杂志,2017,5(1):40-43.
[11] LEOPOLDEO C,DOMENICO C,MAURIM,et al.Intraductal proliferative lesions of the breast terminology and biology matter:premalignant lesions or preinvasive cancer?[J].IntSurg Oncol,2012,2012:501904.
[12] ANNICK P,BERNARD P.The CCN family of proteins:a 25th anniversary picture[J].J Cell Commun Signal,2016,10(3):177-190.
[13] CHAI D M,QIN Y Z,WU S W,et al.WISP-2 exhibits its potenitial antitumor activityvia targeting ERK and E-cadherin pathways in esophageal cancer cells[J].J Exp Clin Cancer Res,2019,38(102):1-15.
[14] JI J F,JIA S Q,JI K,et al.Wnt1 inducible signalling pathway protein-2(WISP-2/CCN5):roles and regulation in human cancer(Review)[J].Oncology Reports,2014,31(2):533-539.
[15] BANERJEE S K,MAITY G,HAQUE I,et al.Human pancreatic cancer progression:an anarchy among CCN-siblings[J].J Cell Communication Signal,2016,10(3):207-216.
[16] ASMAA F,CECILE S,OLIVIER D W,et al.Role of WISP-2/CCN5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells[J].Mol Cell Biol,2008,28(3):1114-1123.
[17] SANDIPTO S,ARNAB G,GARGI M,et al.DCIS to invasive progression in breast is delayed by restoring CCN5[J].AACR Annual Meeting,2017,77(13):1-5.
[18] RIOBO-DEL G N A,LARA M A,WERTHEIMER E V.Role of hedgehog signaling in breast cancer:pathogenesis and therapeutics[J].Cell,2019,25(4):1-45.
[19] ARPEL A,GAMPER C,SPENLE C,et al.Inhibition of primary breast tumor growth and meta stasis using a neuropilin-1 transmembrane domain intering peptide[J].Oncotarget,2016,7(34):54723-54732.
[20] SAXENA N,BANERJEE S,SENGUPTA K,et al.Differential expression of WISP-1 and WISP-2 genes in normal and transformed human breast cell lines[J].Mol Cell Biochem,2001,228:99-104.
[21] LI J,YE L,OWEN S,et al.Emerging role of CCN family protiens in tumorigenesis and cancer metastasis(Review)[J].Int Mol Med,2015,36(6):1451-1463.
[22] DAVIES S R,DAVIES M L,SANDERS A,et al.Differential expression of the CCN family member WISP-1,WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications[J].Int J Oncol,2010,36(5):1129-1136.
[23] BANERJEE S,SAXENA N,SENGUPTA K,et al.WISP-2 gene in human breast cancer:estrogen and progesterone inducible expression and regulation of tumor cell proliferation[J].Neoplasia,2003,5(1):63-73. |