Factors and biomarkers explaining disparities in survival outcomes of early stage gastric cancer between western and eastern world regions

Authors and Affiliations:

Carla Pereira^1,2,3, Ji-Hyeon Park⁴, Sofia Campelos^1,5, Irene Gullo^1,6,7, Carolina Lemos^1,8,9, Leslie Solorzano¹⁰, Diana Martins^1,2,11, Gilza Gonçalves², Dina Leitão^6,7, Hyuk-Joon Lee^4,12,13, Seong-Ho Kong^4,13, Ana André^1,2, Clara Borges¹⁴, Daniela Almeida¹⁴, Carolina Wälbhy¹⁰, Raquel Almeida^1,2,7,15, Woo Ho Kim¹⁶, Fátima Carneiro^1,2,6,7, Han-Kwang Yang^4,12,13, Gabriela M. Almeida^1,2,7, Carla Oliveira^1,2,7

¹ i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

² Ipatimup—Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal

³ Doctoral Programme in Biomedicine, Faculty of Medicine of the University of Porto, Porto, Portugal

⁴ Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea

⁵ Department of Pathology, Ipatimup Diagnostics, Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

⁶ Department of Pathology, Centro Hospitalar Universitário de São João, Porto, Portugal

⁷ Faculty of Medicine of the University of Porto, Porto, Portugal

⁸ UniGENe, IBMC—Institute for Molecular and Cell Biology, Porto, Portugal

⁹  ICBAS—Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

¹⁰ Center for Image Analysis, Department of IT and SciLifeLab, Uppsala University, Uppsala, Sweden

¹¹ Department of Biomedical Laboratory Sciences, ESTeSC—Coimbra Health School, Polytechnic Institute of Coimbra, Coimbra, Portugal

¹² Cancer Research Institute, Seoul National University, Seoul, Republic of Korea

¹³ Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea

¹⁴ Medical Oncology Department, Centro Hospitalar Universitário de São João, Porto, Portugal

¹⁵ Faculty of Sciences of the University of Porto, Porto, Portugal

¹⁶ Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea

Abstract:

Surgical resection with lymphadenectomy and perioperative chemotherapy is the universal mainstay for curative treatment of gastric cancer (GC) patients with locoregional disease. However, GC survival remains asymmetric in West- and East-world regions. We hypothesize that this asymmetry derives from differential clinical management. Therefore, we collected chemo-naïve GC patients from Portugal and South Korea to explore specific immunophenotypic profiles related to disease aggressiveness and clinicopathological factors potentially explaining associated overall survival (OS) differences. Clinicopathological and survival data were collected from chemo-naïve surgical cohorts from Portugal (West-Europe cohort [WE-C]; n = 170) and South Korea (East-Asia cohort [EA-C]; n = 367) and correlated with immunohistochemical expression profiles of E-cadherin and CD44v6 obtained from consecutive tissue microarrays sections. Survival analysis revealed a subset of 12.4% of WE-C patients, whose tumors concomitantly express E-cadherin_abnormal and CD44v6_very high, displaying extremely poor OS, even at TNM stages I and II. These WE-C stage-I and -II patients tumors were particularly aggressive compared to all others, invading deeper into the gastric wall (P = .032) and more often permeating the vasculature (P = .018) and nerves (P = .009). A similar immunophenotypic profile was found in 11.9% of EA-C patients, but unrelated to survival. Tumours, from stage-I and -II EA-C patients, that display both biomarkers, also permeated more lymphatic vessels (P = .003), promoting lymph node (LN) metastasis (P = .019), being diagnosed on average 8 years earlier and submitted to more extensive LN dissection than WE-C. Concomitant E-cadherin_abnormal/CD44v6_very-high expression predicts aggressiveness and poor survival of stage-I and -II GC submitted to conservative lymphadenectomy.

Journal: International Journal of Cancer

Link: https://onlinelibrary.wiley.com/doi/10.1002/ijc.33872