Summary
This study examined the expression of connexin and protease-activated receptor 3 (par-3) in the distal resection margin of rectal cancer and the correlation of the expression of the two proteins with tumor relapse. A total of 40 patients with rectal cancer underwent ultra-low anterior resection with curved cutter stapler. The pathological specimens were divided into 3 groups in terms of sampling sites: tumor group, 2.0-cm group (in which the tissues were harvested 2.0 cm distal to the tumor tissues), 3.0-cm group (in which the tissues were taken 3.0 cm away from the tumor tissues). All the samples were pathologically observed and then measured for the expression of connexin and par-3 by employing immunohistochemistry and Western blotting. The operations in this series went uneventfully. No anastomotic stoma bleeding, stenosis and death occurred postoperatively. Histopathologically, in the tumor group, epithelial cells lost normal pattern of arrangement and polarity, and were loosely connected and even detached. In the 3.0-cm group, the epithelia had normal appearance, obvious cell polarity and essentially intact cell junction. Immunohistochemistry and Western blotting indicated that the 3.0-cm group had the strongest expression of connexin and par-3, and the expression in the 2.0-cm group and the tumor group was relatively weak. There existed significant difference in the expression of the two proteins among the three groups (P<0.05 for all). It was concluded that the down-regulated connexin and par-3 in the distal margin of rectal cancer tissues may indicate the progression of the disease and high likelihood of recurrence and metastasis. Although no tumor cells were found in the sections of the 2.0-cm group, the decreased expression of connexin and par-3 may suggest the development of anaplasia and the increased odds of tumor relapse. Therefore, we are led to speculate that tumor resection only including 2.0 cm of unaffected rectum could not completely avoid the distant metastasis and local relapse.
References
Han FH, Zhang ZD, Zhou ZG, et al. Effect of curved cutter stapler in the ultra low anterior resection for low rectal cancer. Chin J Gastrointestin Surg (Chinese), 2007,10(l):60–63
Meyer L, Meyer F, Dralle H, et al. Insufficiency risk of esophagojejunal anastomosis after total abdominal gastrectomy for gastric carcinoma. Langenbecks Arch Surg, 2005,390(6):510–516
Heald RJ, Moran BJ, Ryall RD, et al. Rectal cancer-the Basingstoke experience of total mesorecal excision, 1978–1997. Arch Surg, 1998,133:894–899
Li N. Advances in molecular resection margin for tumors. J Southeast Univ Med Sci (Chinese), 2008,27,(5): 392–396
Lees-Miller SP. The double (strand break) life of Par-3. Nat Cell Biol, 2007,9(4):363–365
Horikoshi Y, Suzuki A, Yamanaka T, et al. Interaction between PAR-3 and the aPKC-PAR-6 complex is indispensable for apical domain development of epithelial cells. J Cell Sci, 2009,122(Pt 10):1595–1606
Lee HS, Daar IO. EphrinB reverse signaling in cell-cell adhesion: Is it just Par for the course? Cell Adh Migr, 2009,3(3):[Epub ahead of print]
Wang X, Xu Y, Wang F, et al. Aging-related changes of microglia and astrocytes in hypothalamus after intraperitoneal injection of hypertonic saline in rats. J Huazhong Univ Sci Technolog Med Sci, 2006,26(2):231–234
Ueno H, Mochizuki H, Hashiguchi Y, et al. Preoperative parameters expanding the indication of sphincter preserving surgery in patients with advanced low rectal cancer. Ann Surg, 2004,239:34–42
Yano T, Hernandez-Blazquez FJ, Omori Y, et al. Reduction of malignant phenotype of HEPG2 cell is associated with the expression of connexin 26 but not connexin 32. Carcinogenesis, 2001,22(10):1593–1600
Nambara C, Kawasaki Y, Yamasaki H. Role of the cytoplasmic loop domain of Cx43 in its intracellular localization and function: possible interaction with cadherin. J Membr Biol, 2007,217(1–3):63–69
Inose T, Kato H, Kimura H, et al. Correlation between connexin 26 expression and poor prognosis of esophageal squamous cell carcinoma. Ann Surg Oncol, 2009,16(6): 1704–1710
Harikumar R, Thomas N, Mathew T. Small cell carcinoma occurring in a case of ulcerative colitis. Trop Gastroenterol, 2008,29(4): 224–226
Yu Z, Li S, Huang YY, et al. Calcium depletion enhances nectin-1 expression and herpes oncolytic therapy of squamous cell carcinoma. Cancer Gene Ther, 2007,14(8): 738–747
Yu Z, Chan MK, O-charoenrat P, et al. Enhanced nectin-1 expression and herpes oncolytic sensitivity in highly migratory and invasive carcinoma. Clin Cancer Res, 2005,11(13):4889–4897
Wang X, Nie J, Zhou Q, et al. Regulation of Par-3 expression and disruption of Par complex integrity by TGF-beta during the process of epithelial to mesenchymal transition in rat proximal epithelial cells. Biochim Biophys Acta, 2008,1782(1):51–59
Luo Y, Fukuhara M, Weitzman M, et al. Expression of JAM-A, AF-6, PAR-3 and PAR-6 during the assembly and remodeling of RPE tight junctions. Brain Res, 2006,10(1):55–63
Iden S, Rehder D, August B, et al. A distinct PAR complex associates physically with VE-cadherin in vertebrate endothelial cells. EMBO Rep, 2006,7(12):1239–1246
Mizuno K, Suzuki A, Hirose T, et al. Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions. J Biol Chem, 2003,278(33):31 240–31 250
Hirose T, Izumi Y, Nagashima Y, et al. Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. J Cell Sci, 2002,115(12):2485–2495
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Liu, J., Zhang, W., Liu, J. et al. Expressions of connexin and par-3 in the distal margin of rectal cancer after ultra-low anterior resection. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 29, 330–334 (2009). https://doi.org/10.1007/s11596-009-0313-z
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DOI: https://doi.org/10.1007/s11596-009-0313-z