Surgery Today

, Volume 48, Issue 5, pp 478–485 | Cite as

Robust vascular invasion concurrent with intense EGFR immunostaining can predict recurrence in patients with stage IB node-negative gastric cancer

  • Ippeita Araki
  • Marie Washio
  • Keishi Yamashita
  • Kei Hosoda
  • Akira Ema
  • Hiroaki Mieno
  • Hiromitsu Moriya
  • Natsuya Katada
  • Shiro Kikuchi
  • Masahiko Watanabe
Original Article
  • 92 Downloads

Abstract

Purpose

The prognosis of most patients with stage IB node-negative gastric cancer is good without postoperative chemotherapy; however, about 10% suffer recurrence and inevitably die. We conducted this study to establish the optimal indications for postoperative adjuvant chemotherapy in patients at risk of recurrence.

Methods

The subjects of this retrospective study were 124 patients with stage IB node-negative gastric cancer, who underwent gastrectomy at the Kitasato University East Hospital, between 2001 and 2010. We reviewed EGFR immunohistochemistry (IHC) as well as clinicopathological factors.

Results

Of the 124 patients, 47 (38%) showed intense EGFR IHC (2+ or 3+), with significantly less frequency than in stage II/III advanced gastric cancer (p < 0.001). According to univariate analysis, intense EGFR IHC was significantly associated with relapse-free survival (RFS) (p = 0.023) and associated with overall survival (OS) (p = 0.045) as well as vascular invasion (p = 0.031). On the multivariate Cox proportional hazards model, intense EGFR IHC(p = 0.016) was an independent prognostic predictor for RFS, and both vascular invasion (p = 0.033) and intense EGFR IHC (p = 0.031) were independent prognostic predictors for OS. The combination of both factors increased the risk of recurrence (p = 0.001).

Conclusions

In stage IB node-negative gastric cancer, vascular invasion and intense EGFR IHC increase the likelihood of recurrence. We recommend adjuvant chemotherapy for such patients because of the high risk of metachronous recurrence.

Keywords

Gastric cancer Stage IB Vascular invasion EGFR Prognosis 

Notes

Acknowledgements

This study was supported by the Parents’ Association Grant of Kitasato University, School of Medicine.

Compliance with ethical standards

Conflict of interest

Ippeita Araki and his co-authors have no conflicts of interest.

References

  1. 1.
    International Agency for Research on Cancer WHO: GLOBOCAN (2012) Estimated cancer incidence, mortality and prevalence. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
  2. 2.
    Yamashita K, Sakuramoto S, Nemoto M, Shibata T, Mieno H, Katada N, et al. Trend in gastric cancer: 35 years of surgical experience in Japan. World J Gastroenterol. 2011;17:3390–7.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Sakuramoto S, Yamashita K, Kikuchi S, Futawatari N, Katada N, Watanabe M, et al. Laparoscopy versus open distal gastrectomy by expert surgeons for early gastric cancer in Japanese patients: short-term clinical outcomes of a randomized clinical trial. Surg Endosc. 2013;27:1695–705.CrossRefPubMedGoogle Scholar
  4. 4.
    Yamashita K, Sakuramoto S, Shibata T, Nemoto M, Mieno H, Katada N, et al. Survival outcome of laparoscopic gastrectomy for clinical early (cT1) gastric cancer. Surg Today. 2013;43:1013–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Nashimoto A, Akazawa K, Isobe Y, Miyashiro I, Katai H, Kodera Y, et al. Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry. Gastr Cancer. 2013;16:1–27.CrossRefGoogle Scholar
  6. 6.
    Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.CrossRefPubMedGoogle Scholar
  7. 7.
    Ema A, Yamashita K, Sakuramoto S, Wang G, Mieno H, Nemoto M, et al. Lymph node ratio is a critical prognostic predictor in gastric cancer treated with S-1 chemotherapy. Gastr Cancer. 2014;17:67–75.CrossRefGoogle Scholar
  8. 8.
    Yamashita K, Sakuramoto S, Kikuchi S, Katada N, Kobayashi N, Watanabe M. Validation of staging systems for gastric cancer. Gastr Cancer. 2008;11:111–8.CrossRefGoogle Scholar
  9. 9.
    Araki I, Hosoda K, Yamashita K, Katada N, Sakuramoto S, Moriya H, et al. Prognostic impact of venous invasion in stage IB node-negative gastric cancer. Gastr Cancer. 2015;18:297–305.CrossRefGoogle Scholar
  10. 10.
    Terashima M, Kitada K, Ochiai A, Ichikawa W, Kurahashi I, Sakuramoto S, et al. Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Cancer Res. 2012;18:5992–6000.CrossRefPubMedGoogle Scholar
  11. 11.
    Ema A, Yamashita K, Ushiku H, Kojo K, Minatani N, Kikuchi M, et al. Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer. Cancer Sci. 2014;105:1591–600.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ema A, Waraya M, Yamashita K, Kokubo K, Kobayashi H, Hoshi K, et al. Identification of EGFR expression status association with metastatic lymph node density (ND) by expression microarray analysis of advanced gastric cancer. Cancer Med. 2015;4:90–100.CrossRefPubMedGoogle Scholar
  13. 13.
    Japanese Gastric Cancer Association: Japanese classification of gastric carcinoma—2nd english edition. Gastr Cancer. 1998;1:10–24.CrossRefGoogle Scholar
  14. 14.
    Japanese Gastric Cancer Association: Japanese Classification of Gastric Carcinoma—3nd english edition. Gastr Cancer. 2011;14:101–12.CrossRefGoogle Scholar
  15. 15.
    Union for International Cancer Control: TNM classification of malignant tumors, 7th ed. 2009; pp. 73–7.Google Scholar
  16. 16.
    Vergara-Lluri ME, Moatamed NA, Hong E, Apple SK. High concordance between HercepTest immunohistochemistry and ERBB2 fluorescence in situ hybridization before and after implementation of American Society of Clinical Oncology/College of American Pathology 2007 guidelines. Mod Pathol. 2012;25:1326–32.CrossRefPubMedGoogle Scholar
  17. 17.
    Kunisaki C, Shimada H, Nomura M, Matsuda G, Otsuka Y, Ono H, et al. Therapeutic strategy for patients with pN0 gastric carcinoma. J Surg Oncol. 2006;94:212–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Baiocchi GL, Tiberio GA, Minicozzi AM, Morgagni P, Marrelli D, Bruno L, et al. A multicentric Western analysis of prognostic factors in advanced, node-negative gastric cancer patients. Ann Surg. 2010;252:70–3.CrossRefPubMedGoogle Scholar
  19. 19.
    Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25:1670–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMedGoogle Scholar
  21. 21.
    Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015;26:141–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:481–9.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2017

Authors and Affiliations

  • Ippeita Araki
    • 1
  • Marie Washio
    • 1
  • Keishi Yamashita
    • 1
  • Kei Hosoda
    • 1
  • Akira Ema
    • 1
  • Hiroaki Mieno
    • 1
  • Hiromitsu Moriya
    • 1
  • Natsuya Katada
    • 1
  • Shiro Kikuchi
    • 1
  • Masahiko Watanabe
    • 1
  1. 1.Department of SurgeryKitasato University School of MedicineSagamiharaJapan

Personalised recommendations