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Published in: Gastric Cancer 3/2016

01-07-2016 | Original Article

Clinicopathologic features of gastric cancer with synchronous and metachronous colorectal cancer in Korea: are microsatellite instability and p53 overexpression useful markers for predicting colorectal cancer in gastric cancer patients?

Authors: Hee Jin Kim, Nayoung Kim, Yoon Jin Choi, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Hye Seung Lee, Sang-Hoon Ahn, Do Joong Park, Hyung Ho Kim, Il Tae Son, Sung-Bum Kang, Dong Ho Lee

Published in: Gastric Cancer | Issue 3/2016

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Abstract

Background

A large-scale study was performed to identify the risk factors for developing synchronous and metachronous colorectal cancer (CRC) in gastric cancer (GC) patients, including microsatellite instability (MSI) and p53 overexpression.

Methods

A total of 1041 GC patients who underwent endoscopic resection or surgery and underwent colonoscopy simultaneously or during surveillance for GC were consecutively enrolled. Clinicopathologic characteristics, MSI, and p53 overexpression were compared between the GC patients with and those without synchronous and metachronous CRC.

Results

Of the 1041 patients, CRCs were detected in 67 (6.4 %) patients with GC. Forty-six (4.4 %) had synchronous CRC and 21 (2.0 %) had metachronous CRC. Univariate analysis indicated that age ≥63 years (P < 0.001), male sex (P = 0.005), and p53 overexpression (P = 0.040) were significantly associated with a higher incidence of CRC. However, body mass index, smoking, tumor location, tumor multiplicity, tumor histology, TNM stage, and MSI were not significantly associated with the incidence of CRC. Age ≥63 years (OR: 5.881; 95 % CI: 3.083–11.221; P < 0.001) and male sex (OR: 2.933; 95 % CI: 1.307–6.584; P = 0.009) were risk factors for CRC in GC patients according to multivariate analysis.

Conclusions

GC patients who are male and/or ≥63 years old are recommended to receive colonoscopy to detect CRC. MSI and p53 overexpression were not useful molecular markers for predicting CRC in GC.
Literature
1.
go back to reference Ikeda Y, Saku M, Kawanaka H, Nonaka M, Yoshida K. Features of second primary cancer in patients with gastric cancer. Oncology. 2003;65:113–7.CrossRefPubMed Ikeda Y, Saku M, Kawanaka H, Nonaka M, Yoshida K. Features of second primary cancer in patients with gastric cancer. Oncology. 2003;65:113–7.CrossRefPubMed
2.
go back to reference Dinis-Ribeiro M, Lomba-Viana H, Silva R, Moreira-Dias L, Lomba-Viana R. Associated primary tumors in patients with gastric cancer. J Clin Gastroenterol. 2002;34:533–5.CrossRefPubMed Dinis-Ribeiro M, Lomba-Viana H, Silva R, Moreira-Dias L, Lomba-Viana R. Associated primary tumors in patients with gastric cancer. J Clin Gastroenterol. 2002;34:533–5.CrossRefPubMed
3.
go back to reference Cho I, An JY, Kwon IG, Choi YY, Cheong JH, Hyung WJ, et al. Risk factors for double primary malignancies and their clinical implications in patients with sporadic gastric cancer. Eur J Surg Oncol. 2014;40:338–44.CrossRefPubMed Cho I, An JY, Kwon IG, Choi YY, Cheong JH, Hyung WJ, et al. Risk factors for double primary malignancies and their clinical implications in patients with sporadic gastric cancer. Eur J Surg Oncol. 2014;40:338–44.CrossRefPubMed
4.
go back to reference Eom BW, Lee HJ, Yoo MW, Cho JJ, Kim WH, Yang HK, et al. Synchronous and metachronous cancers in patients with gastric cancer. J Surg Oncol. 2008;98:106–10.CrossRefPubMed Eom BW, Lee HJ, Yoo MW, Cho JJ, Kim WH, Yang HK, et al. Synchronous and metachronous cancers in patients with gastric cancer. J Surg Oncol. 2008;98:106–10.CrossRefPubMed
5.
go back to reference Ojima T, Iwahashi M, Nakamori M, Nakamura M, Katsuda M, Iida T, et al. Is preoperative colonoscopy necessary for patients undergoing gastric cancer surgery? Ann Surg Oncol. 2014;21(Suppl 3):S379–84.CrossRefPubMed Ojima T, Iwahashi M, Nakamori M, Nakamura M, Katsuda M, Iida T, et al. Is preoperative colonoscopy necessary for patients undergoing gastric cancer surgery? Ann Surg Oncol. 2014;21(Suppl 3):S379–84.CrossRefPubMed
6.
go back to reference Suzuki A, Koide N, Takeuchi D, Okumura M, Ishizone S, Suga T, et al. Prevalence of synchronous colorectal neoplasms in surgically treated gastric cancer patients and significance of screening colonoscopy. Dig Endosc. 2014;26:396–402.CrossRefPubMed Suzuki A, Koide N, Takeuchi D, Okumura M, Ishizone S, Suga T, et al. Prevalence of synchronous colorectal neoplasms in surgically treated gastric cancer patients and significance of screening colonoscopy. Dig Endosc. 2014;26:396–402.CrossRefPubMed
7.
go back to reference Kim HO, Hwang SI, Yoo CH, Kim H. Preoperative colonoscopy for patients with gastric adenocarcinoma. J Gastroenterol Hepatol. 2009;24:1740–4.CrossRefPubMed Kim HO, Hwang SI, Yoo CH, Kim H. Preoperative colonoscopy for patients with gastric adenocarcinoma. J Gastroenterol Hepatol. 2009;24:1740–4.CrossRefPubMed
8.
go back to reference Park DI, Park SH, Yoo TW, Kim HS, Yang SK, Byeon JS, et al. The prevalence of colorectal neoplasia in patients with gastric cancer: a Korean Association for the Study of Intestinal Disease (KASID) study. J Clin Gastroenterol. 2010;44:102–5. Park DI, Park SH, Yoo TW, Kim HS, Yang SK, Byeon JS, et al. The prevalence of colorectal neoplasia in patients with gastric cancer: a Korean Association for the Study of Intestinal Disease (KASID) study. J Clin Gastroenterol. 2010;44:102–5.
9.
go back to reference Saito S, Hosoya Y, Togashi K, Kurashina K, Haruta H, Hyodo M, et al. Prevalence of synchronous colorectal neoplasms detected by colonoscopy in patients with gastric cancer. Surg Today. 2008;38:20–5.CrossRefPubMed Saito S, Hosoya Y, Togashi K, Kurashina K, Haruta H, Hyodo M, et al. Prevalence of synchronous colorectal neoplasms detected by colonoscopy in patients with gastric cancer. Surg Today. 2008;38:20–5.CrossRefPubMed
10.
go back to reference Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76:1–18.CrossRefPubMedPubMedCentral Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76:1–18.CrossRefPubMedPubMedCentral
11.
go back to reference Kato M, Asaka M, Shimizu Y, Nobuta A, Takeda H, Sugiyama T, et al. Relationship between Helicobacter pylori infection and the prevalence, site and histological type of gastric cancer. Aliment Pharmacol Ther. 2004;20(Suppl 1):85–9. Kato M, Asaka M, Shimizu Y, Nobuta A, Takeda H, Sugiyama T, et al. Relationship between Helicobacter pylori infection and the prevalence, site and histological type of gastric cancer. Aliment Pharmacol Ther. 2004;20(Suppl 1):85–9.
12.
go back to reference Arnold CN, Goel A, Blum HE, Boland CR. Molecular pathogenesis of colorectal cancer: implications for molecular diagnosis. Cancer. 2005;104:2035–47.CrossRefPubMed Arnold CN, Goel A, Blum HE, Boland CR. Molecular pathogenesis of colorectal cancer: implications for molecular diagnosis. Cancer. 2005;104:2035–47.CrossRefPubMed
13.
go back to reference Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer. 2009;125:171–80.CrossRefPubMed Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. Int J Cancer. 2009;125:171–80.CrossRefPubMed
14.
go back to reference Low S, Chin MC, Ma S, Heng D, Deurenberg-Yap M. Rationale for redefining obesity in Asians. Ann Acad Med Singapore. 2009;38:66–9.PubMed Low S, Chin MC, Ma S, Heng D, Deurenberg-Yap M. Rationale for redefining obesity in Asians. Ann Acad Med Singapore. 2009;38:66–9.PubMed
15.
go back to reference Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.
16.
go back to reference Oh JR, Kim DW, Lee HS, Lee HE, Lee SM, Jang JH, et al. Microsatellite instability testing in Korean patients with colorectal cancer. Fam Cancer. 2012;11:459–66.CrossRefPubMed Oh JR, Kim DW, Lee HS, Lee HE, Lee SM, Jang JH, et al. Microsatellite instability testing in Korean patients with colorectal cancer. Fam Cancer. 2012;11:459–66.CrossRefPubMed
17.
go back to reference Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. 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. 1998;58:5248–57.PubMed Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. 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. 1998;58:5248–57.PubMed
18.
go back to reference Lee HK, Lee HS, Yang HK, Kim WH, Lee KU, Choe KJ, et al. Prognostic significance of Bcl-2 and p53 expression in gastric cancer. Int J Colorectal Dis. 2003;18:518–25.CrossRefPubMed Lee HK, Lee HS, Yang HK, Kim WH, Lee KU, Choe KJ, et al. Prognostic significance of Bcl-2 and p53 expression in gastric cancer. Int J Colorectal Dis. 2003;18:518–25.CrossRefPubMed
19.
go back to reference Byeon JS, Yang SK, Kim TI, Kim WH, Lau JY, Leung WK, et al. Colorectal neoplasm in asymptomatic Asians: a prospective multinational multicenter colonoscopy survey. Gastrointest Endosc. 2007;65:1015–22.CrossRefPubMed Byeon JS, Yang SK, Kim TI, Kim WH, Lau JY, Leung WK, et al. Colorectal neoplasm in asymptomatic Asians: a prospective multinational multicenter colonoscopy survey. Gastrointest Endosc. 2007;65:1015–22.CrossRefPubMed
20.
go back to reference Choe JW, Chang HS, Yang SK, Myung SJ, Byeon JS, Lee D, et al. Screening colonoscopy in asymptomatic average-risk Koreans: analysis in relation to age and sex. J Gastroenterol Hepatol. 2007;22:1003–8.CrossRefPubMed Choe JW, Chang HS, Yang SK, Myung SJ, Byeon JS, Lee D, et al. Screening colonoscopy in asymptomatic average-risk Koreans: analysis in relation to age and sex. J Gastroenterol Hepatol. 2007;22:1003–8.CrossRefPubMed
21.
go back to reference Yoo HM, Gweon TG, Seo HS, Shim JH, Oh SI, Choi MG, et al. Role of preoperative colonoscopy in patients with gastric cancer: a case control study of the prevalence of coexisting colorectal neoplasms. Ann Surg Oncol. 2013;20:1614–22.CrossRefPubMed Yoo HM, Gweon TG, Seo HS, Shim JH, Oh SI, Choi MG, et al. Role of preoperative colonoscopy in patients with gastric cancer: a case control study of the prevalence of coexisting colorectal neoplasms. Ann Surg Oncol. 2013;20:1614–22.CrossRefPubMed
22.
23.
go back to reference Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature. 1997;386:623–7.CrossRefPubMed Lengauer C, Kinzler KW, Vogelstein B. Genetic instability in colorectal cancers. Nature. 1997;386:623–7.CrossRefPubMed
24.
go back to reference Uchino S, Tsuda H, Noguchi M, Yokota J, Terada M, Saito T, et al. Frequent loss of heterozygosity at the DCC locus in gastric cancer. Cancer Res. 1992;52:3099–102.PubMed Uchino S, Tsuda H, Noguchi M, Yokota J, Terada M, Saito T, et al. Frequent loss of heterozygosity at the DCC locus in gastric cancer. Cancer Res. 1992;52:3099–102.PubMed
25.
go back to reference Nakatsuru S, Yanagisawa A, Ichii S, Tahara E, Kato Y, Nakamura Y, et al. Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma. Hum Mol Genet. 1992;1:559–63.CrossRefPubMed Nakatsuru S, Yanagisawa A, Ichii S, Tahara E, Kato Y, Nakamura Y, et al. Somatic mutation of the APC gene in gastric cancer: frequent mutations in very well differentiated adenocarcinoma and signet-ring cell carcinoma. Hum Mol Genet. 1992;1:559–63.CrossRefPubMed
26.
go back to reference Kataoka M, Okabayashi T, Johira H, Nakatani S, Nakashima A, Takeda A, et al. Aberration of p53 and DCC in gastric and colorectal cancer. Oncol Rep. 2000;7:99–103.PubMed Kataoka M, Okabayashi T, Johira H, Nakatani S, Nakashima A, Takeda A, et al. Aberration of p53 and DCC in gastric and colorectal cancer. Oncol Rep. 2000;7:99–103.PubMed
27.
go back to reference Fang DC, Luo YH, Yang SM, Li XA, Ling XL, Fang L. Mutation analysis of APC gene in gastric cancer with microsatellite instability. World J Gastroenterol. 2002;8:787–91.CrossRefPubMedPubMedCentral Fang DC, Luo YH, Yang SM, Li XA, Ling XL, Fang L. Mutation analysis of APC gene in gastric cancer with microsatellite instability. World J Gastroenterol. 2002;8:787–91.CrossRefPubMedPubMedCentral
28.
go back to reference Li M, Liu W, Zhu YF, Chen YL, Zhang BZ, Wang R. Correlation of COX-2 and K-ras expression to clinical outcome in gastric cancer. Acta Oncol. 2006;45:1115–9.CrossRefPubMed Li M, Liu W, Zhu YF, Chen YL, Zhang BZ, Wang R. Correlation of COX-2 and K-ras expression to clinical outcome in gastric cancer. Acta Oncol. 2006;45:1115–9.CrossRefPubMed
29.
go back to reference Tanaka M, Omura K, Watanabe Y, Oda Y, Nakanishi I. Prognostic factors of colorectal cancer: K-ras mutation, overexpression of the p53 protein, and cell proliferative activity. J Surg Oncol. 1994;57:57–64.CrossRefPubMed Tanaka M, Omura K, Watanabe Y, Oda Y, Nakanishi I. Prognostic factors of colorectal cancer: K-ras mutation, overexpression of the p53 protein, and cell proliferative activity. J Surg Oncol. 1994;57:57–64.CrossRefPubMed
30.
go back to reference Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(2073–87):e3.PubMed Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138(2073–87):e3.PubMed
31.
go back to reference Veigl ML, Kasturi L, Olechnowicz J, Ma AH, Lutterbaugh JD, Periyasamy S, et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci USA. 1998;95:8698–702.CrossRefPubMedPubMedCentral Veigl ML, Kasturi L, Olechnowicz J, Ma AH, Lutterbaugh JD, Periyasamy S, et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci USA. 1998;95:8698–702.CrossRefPubMedPubMedCentral
32.
go back to reference Hampel H, Stephens JA, Pukkala E, Sankila R, Aaltonen LA, Mecklin JP, et al. Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology. 2005;129:415–21.CrossRefPubMed Hampel H, Stephens JA, Pukkala E, Sankila R, Aaltonen LA, Mecklin JP, et al. Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology. 2005;129:415–21.CrossRefPubMed
33.
go back to reference Ottini L, Falchetti M, Lupi R, Rizzolo P, Agnese V, Colucci G, et al. Patterns of genomic instability in gastric cancer: clinical implications and perspectives. Ann Oncol. 2006;17(Suppl 7):vii97–102.PubMed Ottini L, Falchetti M, Lupi R, Rizzolo P, Agnese V, Colucci G, et al. Patterns of genomic instability in gastric cancer: clinical implications and perspectives. Ann Oncol. 2006;17(Suppl 7):vii97–102.PubMed
34.
go back to reference Falchetti M, Saieva C, Lupi R, Masala G, Rizzolo P, Zanna I, et al. Gastric cancer with high-level microsatellite instability: target gene mutations, clinicopathologic features, and long-term survival. Hum Pathol. 2008;39:925–32.CrossRefPubMed Falchetti M, Saieva C, Lupi R, Masala G, Rizzolo P, Zanna I, et al. Gastric cancer with high-level microsatellite instability: target gene mutations, clinicopathologic features, and long-term survival. Hum Pathol. 2008;39:925–32.CrossRefPubMed
35.
go back to reference Yun HR, Yi LJ, Cho YK, Park JH, Cho YB, Yun SH, et al. Double primary malignancy in colorectal cancer patients—MSI is the useful marker for predicting double primary tumors. Int J Colorectal Dis. 2009;24:369–75. Yun HR, Yi LJ, Cho YK, Park JH, Cho YB, Yun SH, et al. Double primary malignancy in colorectal cancer patients—MSI is the useful marker for predicting double primary tumors. Int J Colorectal Dis. 2009;24:369–75.
36.
go back to reference Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261–8. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261–8.
37.
38.
go back to reference Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis—the p53 network. J Cell Sci. 2003;116:4077–85.CrossRefPubMed Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis—the p53 network. J Cell Sci. 2003;116:4077–85.CrossRefPubMed
39.
40.
go back to reference Sonnenberg A, Genta RM. Helicobacter pylori is a risk factor for colonic neoplasms. Am J Gastroenterol. 2013;108:208–15. Sonnenberg A, Genta RM. Helicobacter pylori is a risk factor for colonic neoplasms. Am J Gastroenterol. 2013;108:208–15.
41.
go back to reference Hong SN, Lee SM, Kim JH, Lee TY, Kim JH, Choe WH, et al. Helicobacter pylori infection increases the risk of colorectal adenomas: cross-sectional study and meta-analysis. Dig Dis Sci. 2012;57:2184–94. Hong SN, Lee SM, Kim JH, Lee TY, Kim JH, Choe WH, et al. Helicobacter pylori infection increases the risk of colorectal adenomas: cross-sectional study and meta-analysis. Dig Dis Sci. 2012;57:2184–94.
42.
go back to reference Nam KW, Baeg MK, Kwon JH, Cho SH, Na SJ, Choi MG. Helicobacter pylori seropositivity is positively associated with colorectal neoplasms. Korean J Gastroenterol. 2013;61:259–64. Nam KW, Baeg MK, Kwon JH, Cho SH, Na SJ, Choi MG. Helicobacter pylori seropositivity is positively associated with colorectal neoplasms. Korean J Gastroenterol. 2013;61:259–64.
43.
go back to reference Georgopoulos SD, Polymeros D, Triantafyllou K, Spiliadi C, Mentis A, Karamanolis DG, et al. Hypergastrinemia is associated with increased risk of distal colon adenomas. Digestion. 2006;74:42–6.CrossRefPubMed Georgopoulos SD, Polymeros D, Triantafyllou K, Spiliadi C, Mentis A, Karamanolis DG, et al. Hypergastrinemia is associated with increased risk of distal colon adenomas. Digestion. 2006;74:42–6.CrossRefPubMed
44.
go back to reference Jones M, Helliwell P, Pritchard C, Tharakan J, Mathew J. Helicobacter pylori in colorectal neoplasms: is there an aetiological relationship? World J Surg Oncol. 2007;5:51. Jones M, Helliwell P, Pritchard C, Tharakan J, Mathew J. Helicobacter pylori in colorectal neoplasms: is there an aetiological relationship? World J Surg Oncol. 2007;5:51.
45.
go back to reference Kim HJ, Hwang SW, Kim N, Yoon H, Shin CM, Park YS, et al. Helicobacter pylori and molecular markers as prognostic indicators for gastric cancer in Korea. J Cancer Prev. 2014;19:56–67.CrossRefPubMedPubMedCentral Kim HJ, Hwang SW, Kim N, Yoon H, Shin CM, Park YS, et al. Helicobacter pylori and molecular markers as prognostic indicators for gastric cancer in Korea. J Cancer Prev. 2014;19:56–67.CrossRefPubMedPubMedCentral
Metadata
Title
Clinicopathologic features of gastric cancer with synchronous and metachronous colorectal cancer in Korea: are microsatellite instability and p53 overexpression useful markers for predicting colorectal cancer in gastric cancer patients?
Authors
Hee Jin Kim
Nayoung Kim
Yoon Jin Choi
Hyuk Yoon
Cheol Min Shin
Young Soo Park
Hye Seung Lee
Sang-Hoon Ahn
Do Joong Park
Hyung Ho Kim
Il Tae Son
Sung-Bum Kang
Dong Ho Lee
Publication date
01-07-2016
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 3/2016
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-015-0552-6

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