Abstract
Purpose
The different pathological characteristics and prognoses between gastric cancer patients coming from high-risk (group A) and low-risk (group B) areas of Italy were analyzed. We investigated a suspected difference in microsatellite instability (MSI) between these two groups.
Methods
MSI analyses of 452 gastric cancer patients were performed using five quasimonomorphic mononucleotide repeats NR-21, NR-24, NR-27, BAT-25, and BAT-26. MSI analysis was done by PCR usage. An allelic profile of these five mononucleotides was detected on an automated DNA sequencer ABI PRISM 3100 Genetic Analyser. Data were analyzed according to high-risk and low-risk gastric cancer areas.
Results
MSI was observed in 23.9 % of all gastric cancer patients studied. Patients from group A showed a higher rate of MSI (28.4 %) than from group B (13.5 %) (p < 0.001). We analyzed this association together with tumor location and Lauren classification: A nonsignificant differences were seen when analyzing cardia and non-cardia tumors (p = 0.854) but significant for Lauren histotype (p = 0.028). There was no statistical difference in survival between high-risk and low-risk areas (p = 0.437), with a nonsignificant trend for better survival in the high-risk group, especially when measured over a longer period of time. Analyzing MSI or MSS in these groups, the survival curves were almost the same.
Conclusions
A higher frequency of MSI in patients coming from high-risk areas may help explain geographical differences in gastric cancer. The trend of better survival in high-risk areas may be due to a higher rate of MSI gastric cancer patients.
Similar content being viewed by others
References
An C, Choi IS, Yao JC, Worah S, Xie K, Mansfield PF, Ajani JA, Rashid A, Hamilton SR, Wu TT (2005) Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma. Clin Cancer Res 11(2 Pt 1):656–663
Ang TL, Fock KM (2014) Clinical epidemiology of gastric cancer. Singapore Med J 55(12):621–628
Arai T, Sakurai U, Sawabe M, Huang KH, Chen JH, Lo SS, Hsieh MC, Li AF, Wu CW, Chiou SH (2013) Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach. Gastric Cancer 16(4):505–512
Beghelli S, de Manzoni G, Barbi S, Tomezzoli A, Roviello F, Di Gregorio C, Vindigni C, Bortesi L, Parisi A, Saragoni L, Scarpa A, Moore PS (2006) Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers. Surgery 139:347–356
Boland CR, Thibodeau SN, Hamilton SR, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58(22):5248–5257
Bollschweiler E, Boettcher K, Hoelscher AH, Sasako M, Kinoshita T, Maruyama K, Siewert JR (1993) Is the prognosis for Japanese and German patients with gastric cancer really different? Cancer 71:2918–2925
Buffart TE, Louw M, van Grieken NC, Tijssen M, Carvalho B, Ylstra B, Grabsch H, Mulder CJ, van de Velde CJ, van der Merwe SW, Meijer GA (2011) Gastric cancers of Western European and African patients show different patterns of genomic instability. BMC Med Genomics 4:7
Buhard O, Suraweera N, Lectard A, Duval A, Hamelin R (2004) Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis. Dis Markers 20(4–5):251–257
Byfield SA, Earle CC, Ayanian JZ, McCarthy EP (2009) Treatment and outcomes of gastric cancer among United States-born and foreign-born Asians and Pacific Islanders. Cancer 115:4595–4605
Calvo F, Sallabanda M, Sole CV, Gonzalez C, Murillo LA, Martinez-Villanueva J, Santos JA, Serrano J, Alavrez A, Blanco J, Calin A, Gomez-Espi M, Lozano M, Herranz R (2014) Intraoperative radiation therapy opportunities for clinical practice normalization: data recording and innovative development. Rep Pract Oncol Radiother 19:246–252
Cancer Genome Atlas Research Network et al (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513(7517):202–209
Chiaravalli AM, Furlan D, Facco C, Tibiletti MG, Dionigi A, Casati B, Albarello L, Riva C, Capella C (2001) Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences. Virchows Arch 438(1):39–48
Cho I, An JY, Kwon IG, Choi YY, Cheong JH, Hyung WJ, Noh SH (2014) Risk factors for double primary malignancies and their clinical implications in patients with sporadic gastric cancer. Eur J Surg Oncol 40(3):338–344
Coleman MP, Gatta G, Verdecchia A, Estève J, Sant M, Storm H, Allemani C, Ciccolallo L, Santaquilani M, Berrino F, EUROCARE Working Group (2003) EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century. Ann Oncol 14(Suppl 5):v128–v149
Corso G, Pedrazzani C, Marrelli D, Pascale V, Pinto E, Roviello F (2009) Correlation of microsatellite instability at multiple loci with long-term survival in advanced gastric carcinoma. Arch Surg 144(8):722–727
Crew KD, Neugut AI (2006) Epidemiology of gastric cancer. World J Gastroenterol 12(3):354–362
Cristescu R, Lee J, Nebozhyn M et al (2015) Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med 21(5):449–456
D’Elia L, Rossi G, Ippolito R, Cappuccio FP, Strazzullo P (2012) Habitual salt intake and risk of gastric cancer: a meta-analysis of prospective studies. Clin Nutr 31:489–498
Fang WL, Chang SC, Lan YT, Huang KH, Chen JH, Lo SS, Hsieh MC, Li AF, Wu CW, Chiou SH (2012) Microsatellite instability is associated with a better prognosis for gastric cancer patients after curative surgery. World J Surg 36(9):2131–2138
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386
Gill S, Shah A, Le N, Cook EF, Yoshida EM (2003) Asian ethnicity-related differences in gastric cancer presentation and outcome among patients treated at a Canadian cancer center. J Clin Oncol 21:2070–2076
Gonzalez CA, Jakszyn P, Pera G et al (2006) Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst 98:345–354
Hayden JD, Cawkwell L, Quirke P, Dixon MF, Goldstone AR, Sue-Ling H, Johnston D, Martin IG (1997) Prognostic significance of microsatellite instability in patients with gastric carcinoma. Eur J Cancer 33(14):2342–2346
Hundahl SA, Phillips JL, Menck HR (2000) The National Cancer Database Report on poor survival of US gastric carcinoma patients treated with gastrectomy: fifth Edition American Joint Committee on Cancer staging, proximal disease, and the “different disease” hypothesis. Cancer 88:921–932
Inghelmann R, Grande E, Francisci S, Verdecchia A, Micheli A, Baili P, Capocaccia R, De Angelis R (2007) Regional estimates of stomach cancer burden in Italy. Tumori 93(4):367–373
Isa N (2014) Evidence based radiation oncology with existing technology. Rep Pract Oncol Radiother 19(6):259–266
Kim J, Mailey B, Senthil M, Artinyan A, Sun CL, Bhatia S (2009) Disparities in gastric cancer outcomes among Asian ethnicities in the USA. Ann Surg Oncol 16:2433–2441
Kim JY, Shin NR, Kim A, Lee HJ, Park WY, Kim JY, Lee CH, Huh GY, do Park Y (2013) Microsatellite instability status in gastric cancer: a reappraisal of its clinical significance and relationship with mucin phenotypes. Korean J Pathol 47(1):28–35
Kirchoff DD, Deutsch GB, Fujita M, Lee DY, Sim MS, Lee JH, Bilchik AJ (2015) Overall survival is impacted by birthplace and not extent of surgery in Asian Americans with resectable gastric cancer. J Gastrointest Surg 19(11):1966–1973
Ladeiras-Lopes R, Pereira AK, Nogueira A, Pinheiro-Torres T, Pinto I, Santos-Pereira R, Lunet N (2008) Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control 19:689–701
Markuszewski M, Polom W, Cytawa W, Czapiewski P, Lass P, Matuszewski M (2015) Comparing real-time fluorescent indocyanine green (ICG) and 99 m Tc-nanocolloid radiotracer navigation in sentinel node biopsy of penile cancer. Clin Genitourin Cancer 13(6):574–580
Marrelli D, Pedrazzani C, Corso G, Neri A, Di Martino M, Pinto E, Roviello F (2009) Different pathological features and prognosis in gastric cancer patients coming from high-risk and low-risk areas of Italy. Ann Surg 250(1):43–50
Marrelli D, Pedrazzani C, Morgagni P, de Manzoni G, Pacelli F, Coniglio A, Marchet A, Saragoni L, Giacopuzzi S, Roviello F, Italian Research Group for Gastric Cancer (2011) Changing clinical and pathological features of gastric cancer over time. Br J Surg 98(9):1273–1283
Marrelli D, Połom K, de Manzoni G, Morgagni P, Baiocchi GL, Roviello F (2015) Multimodal treatment of non-cardia gastric cancer in West: where are we going? World J Gastroenterol 21(26):7954–7969
Marrelli D, Polom K, Pascale V, Vindigni C, Piagnerelli R, De Franco L, Ferrara F, Roviello G, Garosi L, Petrioli R, Roviello F (2016) Strong prognostic value of microsatellite instability in intestinal type non-cardia gastric cancer. Ann Surg Oncol 23(3):943–950
Maruyama K, Sasako M, Kinoshita T, Sano T, Katai H (1996) Surgical treatment for gastric cancer: the Japanese approach. Semin Oncol 23:360–368
Mathiak M, Warneke VS, Behrens HM, Haag J, Böger C, Krüger S, Röcken C (2015) Clinicopathologic characteristics of microsatellite instable gastric carcinomas revisited: urgent need for standardization. Appl Immunohistochem Mol Morphol. doi:10.1097/PAI.0000000000000264
Oki E, Kakeji Y, Zhao Y, Yoshida R, Ando K, Masuda T, Ohgaki K, Morita M, Maehara Y (2009) Chemosensitivity and survival in gastric cancer patients with microsatellite instability. Ann Surg Oncol 16:2510–2515
Palli D, Russo A, Ottini L, Masala G, Saieva C, Amorosi A, Cama A, D’Amico C, Falchetti M, Palmirotta R, Decarli A, Mariani Costantini R, Fraumeni JF Jr (2001) Red meat, family history, and increased risk of gastric cancer with microsatellite instability. Cancer Res 61:5415–5419
Persson C, Canedo P, Machado JC, El-Omar EM, Forman D (2011) Polymorphisms in inflammatory response genes and their association with gastric cancer: a HuGE systematic review and meta-analyses. Am J Epidemiol 173:259–270
Polom W, Markuszewski M, Rho YS, Matuszewski M (2014) Usage of invisible near infrared light (NIR) fluorescence with indocyanine green (ICG) and methylene blue (MB) in urological oncology. Part 1. Cent European. J Urol 67(2):142–148
Sasako M, Sano T, Yamamoto S, Kurokawa Y, Nashimoto A, Kurita A, Hiratsuka M, Tsujinaka T, Kinoshita T, Arai K, Yamamura Y, Okajima K, Japan Clinical Oncology Group (2008) D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med 359:453–462
Seo HM, Chang YS, Joo SH, Kim YW, Park YK, Hong SW, Lee SH (2009) Clinicopathologic characteristics and outcomes of gastric cancers with the MSI-H phenotype. J Surg Oncol 99:143–147
Shim JH, Song KY, Jeon HM, Park CH, Jacks LM, Gonen M, Shah MA, Brennan MF, Coit DG, Strong VE (2014) Is gastric cancer different in Korea and the United States? Impact of tumor location on prognosis. Ann Surg Oncol 21(7):2332–2339
Strong VE, Song KY, Park CH, Jacks LM, Gonen M, Shah M, Coit DG, Brennan MF (2010) Comparison of gastric cancer survival following R0 resection in the United States and Korea using an internationally validated nomogram. Ann Surg 251(4):640–646
Theuer CP, Campbell BS, Peel DJ, Lin F, Carpenter P, Ziogas A, Butler JA (2002) Microsatellite instability in Japanese vs. European American patients with gastric cancer. Arch Surg 137(8):960–965 (discussion 965–966)
Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ (2001) Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 345:784–789
Vasen HF, Blanco I, Aktan-Collan K, Gopie JP et al (2013) Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut 62(6):812–823
Vauhkonen M, Vauhkonen H, Sajantila A, Sipponen P (2005) Differences in genomic instability between intestinal- and diffuse-type gastric cancer. Gastric Cancer 8:238–244
Verdecchia A, Corazziari I, Gatta G, Lisi D, Faivre J, Forman D, EUROCARE Working Group (2004) Explaining gastric cancer survival differences among European countries. Int J Cancer 109:737–741
Verlato G, Di Leo A, Maria Rossi G, de Manzoni G (2012) Epidemiology of gastric cancer and screening programs. In: de Manzoni G, Roviello F, Siquini W (eds) Surgery in the multimodal management of gastric cancer. Springer, Milan
Wanebo HJ, Kennedy BJ, Chmiel J, Steele G Jr, Winchester D, Osteen R (1993) Cancer of the stomach: a patient care study by the American College of Surgeons. Ann Surg 218:583–592
Wu M, Semba S, Oue N, Ikehara N, Yasui W, Yokozaki H (2004) BRAF/K-ras mutation, microsatellite instability, and promoter hypermethylation of hMLH1/MGMT in human gastric carcinomas. Gastric Cancer 7(4):246–253
Yao JC, Tseng JF, Worah S, Hess KR, Mansfield PF, Crane CH, Schnirer II, Reddy S, Chiang SS, Najam A, Yu C, Giacco GG, Xie K, Wu TT, Feig BW, Pisters PW, Ajani JA (2005) Clinicopathologic behavior of gastric adenocarcinoma in Hispanic patients: analysis of a single institution’s experience over 15 years. J Clin Oncol 23:3094–3103
Acknowledgments
This study was funded by Istituto Toscano Tumori (ITT) (Grant No. ITT-2007).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Human and animal rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Polom, K., Marrelli, D., Pascale, V. et al. High-risk and low-risk gastric cancer areas in Italy and its association with microsatellite instability. J Cancer Res Clin Oncol 142, 1817–1824 (2016). https://doi.org/10.1007/s00432-016-2181-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-016-2181-9