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11-06-2015 | Gastric cancer | Book chapter | Article

4. Pathology of Gastric Cancer

Authors: Laura H. Tang, MD, PhD, Luke V. Selby, MD

Publisher: Springer International Publishing

Abstract

Gastric carcinoma represents a group of heterogeneous diseases from its epidemiology, etiology, clinical presentations, pathologic phenotype, and genotype. Management of individual patients with gastric cancer requires the knowledge of all aspects of the disease. This chapter intends to address issues related to pathogenesis, pathobiology, classification and staging, specific diagnostic challenges, and the pathologic assessment post neoadjuvant therapy of gastric carcinoma. Furthermore, recent advances in molecular classification of gastric cancer have served as a valuable adjunct to clinical and pathologic phenotype of the disease. The combined clinical, pathologic, and genetic effort in understanding the disease will certainly facilitate personalized treatment and ultimately improve survival from gastric cancer.

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.PubMedCrossRef

Everett SM, Axon AT. Early gastric cancer in Europe. Gut. 1997;41(2):142–50.PubMedCentralPubMedCrossRef

Folli S, Dente M, Dell’Amore D, Gaudio M, Nanni O, Saragoni L, et al. Early gastric cancer: prognostic factors in 223 patients. Br J Surg. 1995;82(7):952–6.PubMedCrossRef

Hisamichi S. Screening for gastric cancer. World J Surg. 1989;13(1):31–7.PubMedCrossRef

Sue-Ling HM, Martin I, Griffith J, Ward DC, Quirke P, Dixon MF, et al. Early gastric cancer: 46 cases treated in one surgical department. Gut. 1992;33(10):1318–22.PubMedCentralPubMedCrossRef

Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991;265(10):1287–9.PubMedCrossRef

Lewin K, Appelman H. Carcinoma of the stomach. In: Lewin K, Appelman H, editors. Atlas of tumor pathology: tumors of the esophagus and stomach. Washington, DC: Armed Forces Institute of Pathology; 1996. pp. 245–330.

Morales TG. Adenocarcinoma of the gastric cardia. Dig Dis. 1997;15(6):346–56.PubMedCrossRef

Cameron AJ, Lomboy CT, Pera M, Carpenter HA. Adenocarcinoma of the esophagogastric junction and Barrett’s esophagus. Gastroenterology. 1995;109(5):1541–6.PubMedCrossRef

10.

Clark GWB. Is Barrett’s metaplasia the source of adenocarcinomas of the cardia? Arch Surg. 1994;129(6):609.PubMedCrossRef

11.

Wijnhoven BP, Siersema PD, Hop WC, van Dekken H, Tilanus HW. Adenocarcinomas of the distal oesophagus and gastric cardia are one clinical entity. Rotterdam Oesophageal Tumour Study Group. Br J Surg. 1999;86(4):529–35.PubMedCrossRef

12.

Kalish RJ, Clancy PE, Orringer MB, Appelman HD. Clinical, epidemiologic, and morphologic comparison between adenocarcinomas arising in Barrett’s esophageal mucosa and in the gastric cardia. Gastroenterology. 1984;86(3):461–7.PubMed

13.

Safatle-Ribeiro AV, Ribeiro U Jr, Reynolds JC. Gastric stump cancer: what is the risk? Dig Dis. 1998;16(3):159–68.PubMedCrossRef

14.

Toftgaard C. Gastric cancer after peptic ulcer surgery. A historic prospective cohort investigation. Ann Surg. 1989;210(2):159–64.PubMedCentralPubMedCrossRef

15.

Kaminishi M, Shimizu N, Yamaguchi H, Hashimoto M, Sakai S, Oohara T. Different carcinogenesis in the gastric remnant after gastrectomy for gastric cancer. Cancer. 1996;77(8 Suppl):1646–53.PubMedCrossRef

16.

Taylor PR, Mason RC, Filipe MI, Vaja S, Hanley DC, Murphy GM, et al. Gastric carcinogenesis in the rat induced by duodenogastric reflux without carcinogens: morphology, mucin histochemistry, polyamine metabolism, and labelling index. Gut. 1991;32(12):1447–54.PubMedCentralPubMedCrossRef

17.

Kuipers EJ, Uyterlinde AM, Pena AS, Roosendaal R, Pals G, Nelis GF, et al. Long-term sequelae of Helicobacter pylori gastritis. Lancet. 1995;345(8964):1525–8.PubMedCrossRef

18.

Siurala M, Sipponen P, Kekki M. Chronic gastritis: dynamic and clinical aspects. Scand J Gastroenterol Suppl. 1985;109:69–76.PubMedCrossRef

19.

Forman D, Newell DG, Fullerton F, Yarnell JWG, Stacey AR, Wald N, et al. Association between infection with Helicobacter-pylori and risk of gastric-cancer—evidence from a prospective investigation. BMJ. 1991;302(6788):1302–5.PubMedCentralPubMedCrossRef

20.

Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991;325(16):1132–6.PubMedCrossRef

21.

Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325(16):1127–31.PubMedCrossRef

22.

Gologan A, Graham DY, Sepulveda AR. Molecular markers in Helicobacter pylori-associated gastric carcinogenesis. Clin Lab Med. 2005;25(1):197–222.PubMedCrossRef

23.

Beales IL, Davey NJ, Pusey CD, Lechler RI, Calam J. Long-term sequelae of Helicobacter pylori gastritis. Lancet. 1995;346(8971):381–2.PubMedCrossRef

24.

Goodman KJ, Correa P, Tengana Aux HJ, DeLany JP, Collazos T. Nutritional factors and Helicobacter pylori infection in Colombian children. J Pediatr Gastroenterol Nutr. 1997;25(5):507–15.PubMedCrossRef

25.

Fukayama M, Chong JM, Kaizaki Y. Epstein–Barr virus and gastric carcinoma. Gastric Cancer. 1998;1(2):104–14.PubMedCrossRef

26.

Kang GH, Lee S, Kim WH, Lee HW, Kim JC, Rhyu MG, et al. Epstein–Barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma. Am J Pathol. 2002;160(3):787–94.PubMedCentralPubMedCrossRef

27.

Matsusaka K, Kaneda A, Nagae G, Ushiku T, Kikuchi Y, Hino R, et al. Classification of Epstein–Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes. Cancer Res. 2011;71(23):7187–97.PubMedCrossRef

28.

Geddert H, Zur Hausen A, Gabbert HE, Sarbia M. EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1. Anal Cell Pathol (Amst). 2010;33(3):143–9.CrossRef

29.

Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.CrossRef

30.

Hsing AW, Hansson LE, McLaughlin JK, Nyren O, Blot WJ, Ekbom A, et al. Pernicious anemia and subsequent cancer. A population-based cohort study. Cancer. 1993;71(3):745–50.PubMedCrossRef

31.

Gladdy RA, Strong VE, Coit D, Allen PJ, Gerdes H, Shia J, et al. Defining surgical indications for type I gastric carcinoid tumor. Ann Surg Oncol. 2009;16(11):3154–60.PubMedCrossRef

32.

Kim J, Cho YA, Choi WJ, Jeong SH. Gene-diet interactions in gastric cancer risk: a systematic review. World J Gastroenterol. 2014;20(28):9600–10.PubMedCentralPubMed

33.

Palli D. Epidemiology of gastric cancer: an evaluation of available evidence. J Gastroenterol. 2000;35(Suppl 12):84–9.PubMed

34.

Hu Z, Ajani JA, Wei Q. Molecular epidemiology of gastric cancer: current status and future prospects. Gastrointest Cancer Res. 2007;1(1):12–9.PubMedCentralPubMed

35.

Correa P. Diet modification and gastric cancer prevention. J Natl Cancer Inst Monogr. 1992(12):75–8.

36.

Kikugawa K, Kato T, Takeda Y. Formation of a highly mutagenic diazo compound from the bamethan-nitrite reaction. Mutat Res. 1987;177(1):35–43.PubMedCrossRef

37.

Mirvish SS, Grandjean AC, Moller H, Fike S, Maynard T, Jones L, et al. N-nitrosoproline excretion by rural Nebraskans drinking water of varied nitrate content. Cancer Epidemiol Biomarkers Prev. 1992;1(6):455–61.PubMed

38.

Masciari S, Dewanwala A, Stoffel EM, Lauwers GY, Zheng H, Achatz MI, et al. Gastric cancer in individuals with Li–Fraumeni syndrome. Genet Med. 2011;13(7):651–7.PubMedCentralPubMedCrossRef

39.

Gayther SA, Gorringe KL, Ramus SJ, Huntsman D, Roviello F, Grehan N, et al. Identification of germ-line E-cadherin mutations in gastric cancer families of European origin. Cancer Res. 1998;58(18):4086–9.PubMed

40.

Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392(6674):402–5.PubMedCrossRef

41.

Guilford PJ, Hopkins JB, Grady WM, Markowitz SD, Willis J, Lynch H, et al. E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Hum Mutat. 1999;14(3):249–55.PubMedCrossRef

42.

Keller G, Vogelsang H, Becker I, Hutter J, Ott K, Candidus S, et al. Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. Am J Pathol. 1999;155(2):337–42.PubMedCentralPubMedCrossRef

43.

Blair V, Martin I, Shaw D, Winship I, Kerr D, Arnold J, et al. Hereditary diffuse gastric cancer: diagnosis and management. Clin Gastroenterol Hepatol. 2006;4(3):262–75.PubMedCrossRef

44.

Caldas C, Carneiro F, Lynch HT, Yokota J, Wiesner GL, Powell SM, et al. Familial gastric cancer: overview and guidelines for management. J Med Genet. 1999;36(12):873–80.PubMedCentralPubMed

45.

Pharoah PD, Guilford P, Caldas C, International Gastric Cancer Linkage Consortium. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology. 2001;121(6):1348–53.PubMedCrossRef

46.

Huntsman DG, Carneiro F, Lewis FR, MacLeod PM, Hayashi A, Monaghan KG, et al. Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations. N Engl J Med. 2001;344(25):1904–9.PubMedCrossRef

47.

Abraham SC, Nobukawa B, Giardiello FM, Hamilton SR, Wu TT. Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations. Am J Pathol. 2000;157(3):747–54.PubMedCentralPubMedCrossRef

48.

Hofgartner WT, Thorp M, Ramus MW, Delorefice G, Chey WY, Ryan CK, et al. Gastric adenocarcinoma associated with fundic gland polyps in a patient with attenuated familial adenomatous polyposis. Am J Gastroenterol. 1999;94(8):2275–81.PubMedCrossRef

49.

Offerhaus GJ, Entius MM, Giardiello FM. Upper gastrointestinal polyps in familial adenomatous polyposis. Hepatogastroenterology. 1999;46(26):667–9.PubMed

50.

Watanabe H, Enjoji M, Yao T, Ohsato K. Gastric lesions in familial adenomatosis coli: their incidence and histologic analysis. Hum Pathol. 1978;9(3):269–83.PubMedCrossRef

51.

Zwick A, Munir M, Ryan CK, Gian J, Burt RW, Leppert M, et al. Gastric adenocarcinoma and dysplasia in fundic gland polyps of a patient with attenuated adenomatous polyposis coli. Gastroenterology. 1997;113(2):659–63.PubMedCrossRef

52.

Abraham SC, Montgomery EA, Singh VK, Yardley JH, Wu TT. Gastric adenomas: intestinal-type and gastric-type adenomas differ in the risk of adenocarcinoma and presence of background mucosal pathology. Am J Surg Pathol. 2002;26(10):1276–85.PubMedCrossRef

53.

Arnason T, Liang WY, Alfaro E, Kelly P, Chung DC, Odze RD, et al. Morphology and natural history of familial adenomatous polyposis-associated dysplastic fundic gland polyps. Histopathology. 2014;65(3):353–62.PubMedCrossRef

54.

Aarnio M, Salovaara R, Aaltonen LA, Mecklin JP, Jarvinen HJ. Features of gastric cancer in hereditary non-polyposis colorectal cancer syndrome. Int J Cancer. 1997;74(5):551–5.PubMedCrossRef

55.

Chung DC, Rustgi AK. The hereditary nonpolyposis colorectal cancer syndrome: genetics and clinical implications. Ann Intern Med. 2003;138(7):560–70.PubMedCrossRef

56.

Mecklin JP, Jarvinen HJ, Peltokallio P. Cancer family syndrome. Genetic analysis of 22 Finnish kindreds. Gastroenterology. 1986;90(2):328–33.PubMed

57.

Park YJ, Shin KH, Park JG. Risk of gastric cancer in hereditary nonpolyposis colorectal cancer in Korea. Clin Cancer Res. 2000;6(8):2994–8.PubMed

58.

Kimura K, Shinmura K, Hasegawa T, Beppu Y, Yokoyama R, Yokota J. Germline p53 mutation in a patient with multiple primary cancers. Jpn J Clin Oncol. 2001;31(7):349–51.PubMedCrossRef

59.

Kleihues P, Schauble B, zur Hausen A, Esteve J, Ohgaki H. Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol. 1997;150(1):1–13.PubMedCentralPubMed

60.

Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, et al. Peutz–Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet. 1998;18(1):38–43.PubMedCrossRef

61.

Giardiello FM, Brensinger JD, Tersmette AC, Goodman SN, Petersen GM, Booker SV, et al. Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology. 2000;119(6):1447–53.PubMedCrossRef

62.

Noda M, Kodama T, Atsumi M, Nakajima M, Sawai N, Kashima K, et al. Possibilities and limitations of endoscopic resection for early gastric cancer. Endoscopy. 1997;29(5):361–5.PubMedCrossRef

63.

Carneiro F, David L, Seruca R, Castedo S, Nesland JM, Sobrinho-Simoes M. Hyperplastic polyposis and diffuse carcinoma of the stomach. A study of a family. Cancer. 1993;72(2):323–9.PubMedCrossRef

64.

Seruca R, Carneiro F, Castedo S, David L, Lopes C, Sobrinho-Simoes M. Familial gastric polyposis revisited. Autosomal dominant inheritance confirmed. Cancer Genet Cytogenet. 1991;53(1):97–100.PubMedCrossRef

65.

Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988;48(13):3554–60.PubMed

66.

Lauwers GY, Riddell RH. Gastric epithelial dysplasia. Gut. 1999;45(5):784–90.PubMedCentralPubMedCrossRef

67.

Yakirevich E, Resnick MB. Pathology of gastric cancer and its precursor lesions. Gastroenterol Clin North Am. 2013;42(2):261–84.PubMedCrossRef

68.

Kasuga A, Yamamoto Y, Fujisaki J, Okada K, Omae M, Ishiyama A, et al. Clinical characterization of gastric lesions initially diagnosed as low-grade adenomas on forceps biopsy. Dig Endosc. 2012;24(5):331–8.PubMedCrossRef

69.

Ghandur-Mnaymneh L, Paz J, Roldan E, Cassady J. Dysplasia of nonmetaplastic gastric mucosa. A proposal for its classification and its possible relationship to diffuse-type gastric carcinoma. Am J Surg Pathol. 1988;12(2):96–114.PubMedCrossRef

70.

Carneiro F, Huntsman DG, Smyrk TC, Owen DA, Seruca R, Pharoah P, et al. Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening. J Pathol. 2004;203(2):681–7.PubMedCrossRef

71.

Borrmann R. Geshwulste des Magens und Duodenums. In: Henke F, Lubarsch O, editors. Handbuch der Speziellen Patho-logischen Anatomie und Histologie. Berlin: Springer-Verlag; 1926. p. 865.

72.

Tan IB, Ivanova T, Lim KH, Ong CW, Deng N, Lee J, et al. Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy. Gastroenterology. 2011;141(2):476–85, 485.e1–11.PubMedCentralPubMedCrossRef

73.

Shah MA, Khanin R, Tang L, Janjigian YY, Klimstra DS, Gerdes H, et al. Molecular classification of gastric cancer: a new paradigm. Clin Cancer Res. 2011;17(9):2693–701.PubMedCentralPubMedCrossRef

74.

Ming SC. Gastric carcinoma. A pathobiological classification. Cancer. 1977;39(6):2475–85.PubMedCrossRef

75.

Goseki N, Takizawa T, Koike M. Differences in the mode of the extension of gastric cancer classified by histological type: new histological classification of gastric carcinoma. Gut. 1992;33(5):606–12.PubMedCentralPubMedCrossRef

76.

Carneiro F, Seixas M, Sobrinho-Simoes M. New elements for an updated classification of the carcinomas of the stomach. Pathol Res Pract. 1995;191(6):571–84.PubMedCrossRef

77.

Laurén P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma—an attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31–49.PubMed

78.

Fenoglio-Preiser C, Carneiro F, Correa P, Guilford P, Lambert R, Megraud F, et al. Tumors of the stomach. In: Hamilton SR, Aaltonen LA, editors. World health organization classification of tumours: pathology and genetics of tumours of the digestive system. Lyon: IARCPress; 2000. pp. 37–52.

79.

Luebke T, Baldus SE, Grass G, Bollschweiler E, Thiele J, Dienes HP, et al. Histological grading in gastric cancer by Ming classification: correlation with histopathological subtypes, metastasis, and prognosis. World J Surg. 2005;29(11):1422–7 (discussion 8).PubMedCrossRef

80.

Lee H, Tang LH, Veras EF, Klimstra DS. The prevalence of pancreatic acinar differentiation in gastric adenocarcinoma: report of a case and immunohistochemical study of 111 additional cases. Am J Surg Pathol. 2012;36(3):402–8.PubMedCrossRef

81.

Liu Z, Mira JL, Cruz-Caudillo JC. Primary gastric choriocarcinoma: a case report and review of the literature. Arch Pathol Lab Med. 2001;125(12):1601–4.PubMed

82.

Niederau C, Sobin LH. Secondary tumors of the stomach. In: Hamilton SR, Aaltonen LA, editors. World health organization classification of tumours: pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000. pp. 66–7.

83.

Oda, Kondo H, Yamao T, Saito D, Ono H, Gotoda T, et al. Metastatic tumors to the stomach: analysis of 54 patients diagnosed at endoscopy and 347 autopsy cases. Endoscopy. 2001;33(6):507–10.PubMedCrossRef

84.

Spicer J, Benay C, Lee L, Rousseau M, Andalib A, Kushner Y, et al. Diagnostic accuracy and utility of intraoperative microscopic margin analysis of gastric and esophageal adenocarcinoma. Ann Surg Oncol. 2014;21(8):2580–6.PubMedCrossRef

85.

Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. 2010.

86.

Mansour JC, Tang L, Shah M, Bentrem D, Klimstra DS, Gonen M, et al. Does graded histologic response after neoadjuvant chemotherapy predict survival for completely resected gastric cancer? Ann Surg Oncol. 2007;14(12):3412–8.PubMedCrossRef

87.

Ryan R, Gibbons D, Hyland JM, Treanor D, White A, Mulcahy HE, et al. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005;47(2):141–6.PubMedCrossRef

88.

Correa P, Shiao YH. Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res. 1994;54(7 Suppl):1941s-3s.

89.

Fuchs CS, Mayer RJ. Gastric carcinoma. N Engl J Med. 1995;333(1):32–41.PubMedCrossRef

90.

Wright PA, Williams GT. Molecular biology and gastric carcinoma. Gut. 1993;34(2):145–7.PubMedCentralPubMedCrossRef

91.

Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345(11):784–9.PubMedCrossRef

92.

Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, et al. Recent patterns in gastric cancer: a global overview. Int J Cancer. 2009;125(3):666–73.PubMedCrossRef

93.

Richards FM, McKee SA, Rajpar MH, Cole TR, Evans DG, Jankowski JA, et al. Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Hum Mol Genet. 1999;8(4):607–10.PubMedCrossRef

94.

Keller G, Grimm V, Vogelsang H, Bischoff P, Mueller J, Siewert JR, et al. Analysis for microsatellite instability and mutations of the DNA mismatch repair gene hMLH1 in familial gastric cancer. Int J Cancer. 1996;68(5):571–6.PubMedCrossRef

95.

Toyota M, Ahuja N, Suzuki H, Itoh F, Ohe-Toyota M, Imai K, et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res. 1999;59(21):5438–42.PubMed

96.

Lei Z, Tan IB, Das K, Deng N, Zouridis H, Pattison S, et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology. 2013;145(3):554–65.PubMedCrossRef

97.

Boussioutas A, Li H, Liu J, Waring P, Lade S, Holloway AJ, et al. Distinctive patterns of gene expression in premalignant gastric mucosa and gastric cancer. Cancer Res. 2003;63(10):2569–77.PubMed

98.

Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, et al. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet. 2011;43(12):1219–23.PubMedCrossRef

99.

Hamilton SR, Aaltonen LA, editors. World health organization classification of tumours: pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000.

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