Sialyl Lewisx expression at the invasive front as a predictive marker of liver recurrence in stage II colorectal cancer

Yamadera,Masato; Shinto,Eiji; Tsuda,Hitoshi; Kajiwara,Yoshiki; Naito,Yoshihisa; Hase,Kazuo; Yamamoto,Junji; Ueno,Hideki

doi:10.3892/ol.2017.7340

Sialyl Lewisx expression at the invasive front as a predictive marker of liver recurrence in stage II colorectal cancer

Authors:
- Masato Yamadera
- Eiji Shinto
- Hitoshi Tsuda
- Yoshiki Kajiwara
- Yoshihisa Naito
- Kazuo Hase
- Junji Yamamoto
- Hideki Ueno
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Affiliations: Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359‑8513, Japan, Department of Pathology, National Defense Medical College, Tokorozawa, Saitama 359‑8513, Japan, Department of Surgery, Teikyo University School of Medicine University Hospital, Mizonokuchi, Kanagawa 213-8507, Japan
Published online on: November 3, 2017 https://doi.org/10.3892/ol.2017.7340
Pages: 221-228
Copyright: © Yamadera et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sialyl Lewisx (SLX) is a carbohydrate ligand for endothelial selectin that participates in cell adhesion, proliferation and scattering. It plays an important role in cancer cell adhesion to vascular endothelial cells, leading to hematogenous metastasis. The prognostic significance of SLX expression level at the invasive front in patients with stage II colorectal cancer (CRC) was examined. A total of 209 patients with stage II CRC curatively resected between 1997 and 2000 were enrolled. The preoperative serum SLX levels measured by radioimmunoassay and SLX immunoexpression levels at the invasive front, and at the non‑invasive frontal region determined by tissue microarray were analyzed. SLX expression at the invasive front was positively associated with tumor invasion depth (P=0.007) and tumor budding grade (P=0.038). Disease‑free survival curves differed between the high and low SLX‑expression groups (5‑year survival rates, 77.0 and 89.7%, respectively; P=0.036). Liver cancer recurrence was more frequent in the high‑expression group than in the low‑expression group (15.9 and 2.4%; P=0.002). Multivariate analysis revealed that its expression (hazard ratio, 5.26; P=0.015) and venous invasion (hazard ratio, 4.14; P=0.040) were independent predictive markers of liver cancer recurrence. Neither the preoperative serum SLX level nor SLX expression at the non‑invasive frontal region showed any association with histopathological features or disease‑free survival. SLX expression level at the invasive front is a promising marker for identifying patients with stage II CRC with a high risk of liver cancer recurrence.

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1	Ueno H, Price AB, Wilkinson KH, Jass JR, Mochizuki H and Talbot IC: A new prognostic staging system for rectal cancer. Ann Surg. 240:832–839. 2004. View Article : Google Scholar
2	Ueno H, Murphy J, Jass JR, Mochizuki H and Talbot IC: Tumor ‘budding’ as an index to estimate the potential of aggressiveness in rectal cancer. Histopathology. 40:127–132. 2002. View Article : Google Scholar
3	Hase K, Shatney C, Johnson D, Trollope M and Vierra M: Prognostic value of tumor ‘budding℉ in patients with colorectal cancer. Dis Colon Rectum. 36:627–635. 1993. View Article : Google Scholar
4	Rogers AC, Winter DC, Heeney A, Gibbons D, Lugli A, Puppa G and Sheahan K: Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br J Cancer. 115:831–840. 2016. View Article : Google Scholar : PubMed/NCBI
5	Fukazawa S, Shinto E, Tsuda H, Ueno H, Shikina A, Kajiwara Y, Yamamoto J and Hase K: Laminin β3 expression as a prognostic factor and a predictive marker of chemoresistance in colorectal cancer. Jpn J Clin Oncol. 45:533–540. 2015.PubMed/NCBI
6	Shinto E, Tsuda H, Ueno H, Hashiguchi Y, Hase K, Tamai S, Mochizuki H, Inazawa J and Matsubara O: Prognostic implication of laminin-5 gamma 2 chain expression in the invasive front of colorectal cancers, disclosed by area-specific four-point tissue microarrays. Lab Invest. 85:257–266. 2005. View Article : Google Scholar : PubMed/NCBI
7	Masaki T, Goto A, Sugiyama M, Matsuoka H, Abe N, Sakamoto A and Atomi Y: Possible contribution of CD44 variant 6 and nuclear beta-catenin expression to the formation of budding tumor cells in patients with T1 colorectal carcinoma. Cancer. 92:2539–2546. 2001. View Article : Google Scholar : PubMed/NCBI
8	Kajiwara Y, Ueno H, Hashiguchi Y, Shinto E, Shimazaki H, Mochizuki H and Hase K: Expression of l1 cell adhesion molecule and morphologic features at the invasive front of colorectal cancer. Am J Clin Pathol. 136:138–144. 2011. View Article : Google Scholar : PubMed/NCBI
9	Kononen J, Bubendorf L, Kallioniemi A, Bärlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G and Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 4:844–847. 1998. View Article : Google Scholar : PubMed/NCBI
10	Kannagi R, Izawa M, Koike T, Miyazaki K and Kimura N: Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci. 95:377–384. 2004. View Article : Google Scholar : PubMed/NCBI
11	Akamine S, Nakagoe T, Sawai T, Tsuji T, Tanaka K, Hidaka S, Shibasaki S, Nanashima A, Yamaguchi H, Nagayasu T and Yasutake T: Differences in prognosis of colorectal cancer patients based on the expression of sialyl Lewisa, sialyl Lewisx and sialyl Tn antigens in serum and tumor tissue. Anticancer Res. 24:2541–2546. 2004.PubMed/NCBI
12	Nakagoe T, Fukushima K, Tanaka K, Sawai T, Tsuji T, Jibiki M, Nanashima A, Yamaguchi H, Yasutake T, Ayabe H and Arisawa K: Evaluation of sialyl Lewis(a), sialyl Lewis(x), and sialyl Tn antigens expression levels as predictors of recurrence after curative surgery in node-negative colorectal cancer patients. J Exp Clin Cancer Res. 21:107–113. 2002.PubMed/NCBI
13	Hoff SD, Matsushita Y, Ota DM, Cleary KR, Yamori T, Hakomori S and Irimura T: Increased expression of sialyl-dimeric LeX antigen in liver metastases of human colorectal carcinoma. Cancer Res. 49:6883–6888. 1989.PubMed/NCBI
14	Schiffmann L, Schwarz F, Linnebacher M, Prall F, Pahnke J, Krentz H, Vollmar B and Klar E: A novel sialyl Le(X) expression score as a potential prognostic tool in colorectal cancer. World J Surg Oncol. 10:952012. View Article : Google Scholar : PubMed/NCBI
15	Ono M, Sakamoto M, Ino Y, Moriya Y, Sugihara K, Muto T and Hirohashi S: Cancer cell morphology at the invasive front and expression of cell adhesion-related carbohydrate in the primary lesion of patients with colorectal carcinoma with liver metastasis. Cancer. 78:1179–1186. 1996. View Article : Google Scholar : PubMed/NCBI
16	Japanese Society for Cancer of the Colon and Rectum, . Japanese Classification of Colorectal Carcinoma. 2nd. Kanehara & Co., Ltd.; Tokyo: 2009
17	Landis JR and Koch GG: The measurement of observer agreement for categorical data. Biometrics. 33:159–174. 1977. View Article : Google Scholar : PubMed/NCBI
18	Weinberg RA: The biology of cancer. 2nd. Garland Science; New York, NY: pp. 685–689. 2014, PubMed/NCBI
19	Leber MF and Efferth T: Molecular principles of cancer invasion and metastasis (Review). Int J Oncol. 34:881–895. 2009.PubMed/NCBI
20	Takada A, Ohmori K, Yoneda T, Tsuyuoka K, Hasegawa A, Kiso M and Kannagi R: Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium. Cancer Res. 53:354–361. 1993.PubMed/NCBI
21	Gassmann P, Haier J, Schlüter K, Domikowsky B, Wendel C, Wiesner U, Kubitza R, Engers R, Schneider SW, Homey B and Müller A: CXCR4 regulates the early extravasation of metastatic tumor cells in vivo. Neoplasia. 11:651–661. 2009. View Article : Google Scholar : PubMed/NCBI
22	Fujisaki T, Tanaka Y, Fujii K, Mine S, Saito K, Yamada S, Yamashita U, Irimura T and Eto S: CD44 stimulation induces integrin-mediated adhesion of colon cancer cell lines to endothelial cells by up-regulation of integrins and c-Met and activation of integrins. Cancer Res. 59:4427–4434. 1999.PubMed/NCBI
23	Nakagoe T, Sawai T, Tsuji T, Jibiki M, Ohbatake M, Nanashima A, Yamaguchi H, Yasutake T, Ayabe H and Tagawa Y: Differences in release mechanisms and distributions for sialyl Le(a) and sialyl Le(x) antigens in colorectal cancer. Ann Surg Oncol. 7:289–295. 2000. View Article : Google Scholar : PubMed/NCBI
24	Nakagoe T, Sawai T, Tsuji T, Jibiki M, Ohbatake M, Nanashima A, Yamaguchi H, Yasutake T, Ayabe H and Arisawa K: Prognostic value of serum sialyl Lewis(a), sialyl Lewis(x) and sialyl Tn antigens in blood from the tumor drainage vein of colorectal cancer patients. Tumour Biol. 22:115–122. 2001. View Article : Google Scholar : PubMed/NCBI
25	Berman JM, Cheung RJ and Weinberg DS: Surveillance after colorectal cancer resection. Lancet. 355:395–399. 2000. View Article : Google Scholar : PubMed/NCBI
26	Leporrier J, Maurel J, Chiche L, Bara S, Segol P and Launoy G: A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg. 93:465–474. 2006. View Article : Google Scholar : PubMed/NCBI
27	Kanas GP, Taylor A, Primrose JN, Langeberg WJ, Kelsh MA, Mowat FS, Alexander DD, Choti MA and Poston G: Survival after liver resection in metastatic colorectal cancer: Review and meta-analysis of prognostic factors. Clin Epidemiol. 4:283–301. 2012.PubMed/NCBI
28	House MG, Ito H, Gönen M, Fong Y, Allen PJ, DeMatteo RP, Brennan MF, Blumgart LH, Jarnagin WR and D'Angelica MI: Survival after hepatic resection for metastatic colorectal cancer: Trends in outcomes for 1,600 patients during two decades at a single institution. J Am Coll Surg. 210:744–755. 2010. View Article : Google Scholar : PubMed/NCBI
29	Watanabe T, Itabashi M, Shimada Y, Tanaka S, Ito Y, Ajioka Y, Hamaguchi T, Hyodo I, Igarashi M, Ishida H, et al: Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol. 17:1–29. 2012. View Article : Google Scholar : PubMed/NCBI
30	Schmoll HJ, Van Custem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, et al: ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol. 23:2479–2516. 2012. View Article : Google Scholar : PubMed/NCBI
31	Benson AB III, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, Krzyzanowska MK, Maroun J, McAllister P, Van Cutsem E, et al: American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 22:3408–3419. 2004. View Article : Google Scholar : PubMed/NCBI