The prognostic significance of lymphovascular invasion in patients with resectable gastric cancer: a large retrospective study from Southern China

Peng Li, Hao-Qiang He, Chong-Mei Zhu, Yi-Hong Ling, Wan-Ming Hu, Xin-Ke Zhang, Rong-Zhen Luo, Jing-Ping Yun, Dan Xie, Yuan-Fang Li, Mu-Yan Cai, Peng Li, Hao-Qiang He, Chong-Mei Zhu, Yi-Hong Ling, Wan-Ming Hu, Xin-Ke Zhang, Rong-Zhen Luo, Jing-Ping Yun, Dan Xie, Yuan-Fang Li, Mu-Yan Cai

Abstract

Background: The focus of this study was to assess the impact of lymphovascular invasion (LVI) on both the recurrence of cancer and the long-term survival of Chinese patients with resectable gastric cancer (GC).

Methods: A retrospective analysis of the clinicopathological data for 1148 GC patients who had undergone gastrectomy with regional lymphadenectomy was performed. The primary objective was to assess the correlation between LVI and post-surgery outcomes for each patient. This was done by routine H & E staining for LVI on patients' disease-free survival (DFS) and disease-specific survival (DSS).

Results: LVI was detected in 404 (35.2%) of the 1148 GC patients. The presence of LVI was significantly correlated with the level of CA19-9, the tumor size, the Lauren classification, tumor differentiation, gastric wall invasive depth, lymph node involvement, distant metastasis and an advanced TNM stage. There was a lower DFS and DSS in the patients with LVI as compared to the patients without LVI. A multivariate analysis also identified LVI as an independent prognostic factor of both DSS and DFS.

Conclusions: The presence of LVI is a risk factor for the recurrence of cancer and an independent indicator of a poor outcome in GC patients following surgery. The LVI status should be taken into consideration when determining the best approach for the treatment of the individual.

Figures

Figure 1
Figure 1
Histological patterns of lymphovascular invasion in gastric cancer.(A) Vessel walls were invaded by tumor cells. (B) Tumor emboli were observed within an endothelium-lined space.
Figure 2
Figure 2
The impact of lymphovascular invasion on the prognosis of patients with gastric cancer (log-rank test). There was a statistically significant difference in the disease-specific survival (A) and disease-free survival (B) between lymphovascular invasion-positive and -negative patients.
Figure 3
Figure 3
The prognostic significance of lymphovascular invasion in patients stratified by the TNM stage (log-rank test). Stage-match survival analysis showed that the presence of LVI was a prognostic factor for DSS in GC patients with stage I, stage II, stage III or stage IV (A-D). Stage-match survival analysis demonstrated that LVI was a statistically significant predictor for DFS in stage I or stage III and a tendency towards statistical significance was found in stage II (P = 0.086) or stage IV (P = 0.067, E-H).

References

    1. Desai AM, Pareek M, Nightingale PG, Fielding JW. Improving outcomes in gastric cancer over 20 years. Gastric Cancer. 2004;7(4):196–201. doi: 10.1007/s10120-004-0289-0.
    1. Rahman R, Asombang AW, Ibdah JA. Characteristics of gastric cancer in Asia. World J Gastroenterol. 2014;20(16):4483–90. doi: 10.3748/wjg.v20.i16.4483.
    1. Cuschieri A, Weeden S, Fielding J, Bancewicz J, Craven J, Joypaul V, et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Br J Cancer. 1999;79(9-10):1522–30. doi: 10.1038/sj.bjc.6690243.
    1. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20. doi: 10.1056/NEJMoa055531.
    1. Zhang J, Zhou Y, Jiang K, Shen Z, Ye Y, Wang S. Evaluation of the seventh AJCC TNM staging system for gastric cancer: a meta-analysis of cohort studies. Tumour Biol. 2014;35(9):8525–32. doi: 10.1007/s13277-014-1848-6.
    1. Mohammed RA, Martin SG, Gill MS, Green AR, Paish EC, Ellis IO. Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences. Am J Surg Pathol. 2007;31(12):1825–33. doi: 10.1097/PAS.0b013e31806841f6.
    1. Zlobec I, Baker K, Minoo P, Jass JR, Terracciano L, Lugli A. Node-negative colorectal cancer at high risk of distant metastasis identified by combined analysis of lymph node status, vascular invasion, and Raf-1 kinase inhibitor protein expression. Clin Cancer Res. 2008;14(1):143–8. doi: 10.1158/1078-0432.CCR-07-1380.
    1. Mete O, Asa SL. Pathological definition and clinical significance of vascular invasion in thyroid carcinomas of follicular epithelial derivation. Mod Pathol. 2011;24(12):1545–52. doi: 10.1038/modpathol.2011.119.
    1. Maeda R, Yoshida J, Ishii G, Hishida T, Nishimura M, Nagai K. Prognostic impact of intratumoral vascular invasion in non-small cell lung cancer patients. Thorax. 2010;65(12):1092–8. doi: 10.1136/thx.2010.141861.
    1. Pichler M, Hutterer GC, Chromecki TF, Jesche J, Groselj-Strele A, Kampel-Kettner K, et al. Prognostic value of the Leibovich prognosis score supplemented by vascular invasion for clear cell renal cell carcinoma. J Urol. 2012;187(3):834–9. doi: 10.1016/j.juro.2011.10.155.
    1. Kikuchi E, Margulis V, Karakiewicz PI, Roscigno M, Mikami S, Lotan Y, et al. Lymphovascular invasion predicts clinical outcomes in patients with node-negative upper tract urothelial carcinoma. J Clin Oncol. 2009;27(4):612–8. doi: 10.1200/JCO.2008.17.2361.
    1. Bu Z, Zheng Z, Li Z, Zhang L, Wu A, Wu X, et al. Lymphatic vascular invasion is an independent correlated factor for lymph node metastasis and the prognosis of resectable T2 gastric cancer patients. Tumour Biol. 2013;34(2):1005–12. doi: 10.1007/s13277-012-0637-3.
    1. Setala LP, Kosma VM, Marin S, Lipponen PK, Eskelinen MJ, Syrjanen KJ, et al. Prognostic factors in gastric cancer: the value of vascular invasion, mitotic rate and lymphoplasmacytic infiltration. Br J Cancer. 1996;74(5):766–72. doi: 10.1038/bjc.1996.434.
    1. Maehara Y, Kabashima A, Koga T, Tokunaga E, Takeuchi H, Kakeji Y, et al. Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma. Surgery. 2000;128(3):408–16. doi: 10.1067/msy.2000.107265.
    1. Cao F, Hu YW, Li P, Liu Y, Wang K, Ma L, et al. Lymphangiogenic and angiogenic microvessel density in chinese patients with gastric carcinoma: correlation with clinicopathologic parameters and prognosis. Asian Pac J Cancer Prev. 2013;14(8):4549–52. doi: 10.7314/APJCP.2013.14.8.4549.
    1. Kim JH, Park SS, Park SH, Kim SJ, Mok YJ, Kim CS, et al. Clinical significance of immunohistochemically-identified lymphatic and/or blood vessel tumor invasion in gastric cancer. J Surg Res. 2010;162(2):177–83. doi: 10.1016/j.jss.2009.07.015.
    1. Gresta LT, Rodrigues-Junior IA, de Castro LP, Cassali GD, Cabral MM. Assessment of vascular invasion in gastric cancer: a comparative study. World J Gastroenterol. 2013;19(24):3761–9. doi: 10.3748/wjg.v19.i24.3761.
    1. Gabbert HE, Meier S, Gerharz CD, Hommel G. Incidence and prognostic significance of vascular invasion in 529 gastric-cancer patients. Int J Cancer. 1991;49(2):203–7. doi: 10.1002/ijc.2910490210.
    1. Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol. 2002;20(6):1527–36. doi: 10.1200/JCO.20.6.1527.
    1. Albers P, Siener R, Kliesch S, Weissbach L, Krege S, Sparwasser C, et al. Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group Trial. J Clin Oncol. 2003;21(8):1505–12. doi: 10.1200/JCO.2003.07.169.
    1. NCCN. Clinical Practice Guidelines in Oncology: Gastric Cancer, Version 2. 2013. National Comprehensive Cancer Network, Inc. . Accessed July 23, 2013.
    1. del Casar JM, Corte MD, Alvarez A, Garcia I, Bongera M, Gonzalez LO, et al. Lymphatic and/or blood vessel invasion in gastric cancer: relationship with clinicopathological parameters, biological factors and prognostic significance. J Cancer Res Clin Oncol. 2008;134(2):153–61. doi: 10.1007/s00432-007-0264-3.
    1. Lee AH, Pinder SE, Macmillan RD, Mitchell M, Ellis IO, Elston CW, et al. Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma. Eur J Cancer. 2006;42(3):357–62. doi: 10.1016/j.ejca.2005.10.021.
    1. Betge J, Pollheimer MJ, Lindtner RA, Kornprat P, Schlemmer A, Rehak P, et al. Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting. Cancer. 2012;118(3):628–38. doi: 10.1002/cncr.26310.
    1. Ruffini E, Asioli S, Filosso PL, Buffoni L, Bruna MC, Mossetti C, et al. Significance of the presence of microscopic vascular invasion after complete resection of Stage I-II pT1-T2N0 non-small cell lung cancer and its relation with T-Size categories: did the 2009 7th edition of the TNM staging system miss something? J Thorac Oncol. 2011;6(2):319–26. doi: 10.1097/JTO.0b013e3182011f70.
    1. Du CY, Chen JG, Zhou Y, Zhao GF, Fu H, Zhou XK, et al. Impact of lymphatic and/or blood vessel invasion in stage II gastric cancer. World J Gastroenterol. 2012;18(27):3610–6. doi: 10.3748/wjg.v18.i27.3610.
    1. Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335(7):462–7. doi: 10.1056/NEJM199608153350702.
    1. Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379(9813):315–21. doi: 10.1016/S0140-6736(11)61873-4.
    1. Lu J, Huang CM, Zheng CH, Li P, Xie JW, Wang JB, et al. Analysis on the clinical and pathological features and prognosis of familial gastric cancer in South china population: a single-center study of 724 patients. J Oncol. 2012;2012:641218. doi: 10.1155/2012/641218.
    1. Zheng L, Wu C, Xi P, Zhu M, Zhang L, Chen S, et al. The survival and the long-term trends of patients with gastric cancer in Shanghai, China. BMC Cancer. 2014;14:300. doi: 10.1186/1471-2407-14-300.
    1. Wang J, Sun Y, Bertagnolli MM. Comparison of gastric cancer survival between caucasian and Asian patients treated in the United States: results from the Surveillance Epidemiology and End Results (SEER) Database. Ann Surg Oncol. 2015. [Epub ahead of print].
    1. Lui FH, Tuan B, Swenson SL, Wong RJ. Ethnic disparities in gastric cancer incidence and survival in the USA: an updated analysis of 1992-2009 SEER data. Dig Dis Sci. 2014;59(12):3027–34. doi: 10.1007/s10620-014-3275-3.
    1. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ. Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial. Lancet Oncol. 2010;11(5):439–49. doi: 10.1016/S1470-2045(10)70070-X.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi