Clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation and gastric adenocarcinoma with enteroblastic marker expression.
Aggressive behavior
Clear cytoplasm
Enteroblastic marker positive gastric adenocarcinoma
Gastric adenocarcinoma with enteroblastic differentiation
Lymphatic invasion
Venous invasion
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
29
05
2023
accepted:
07
08
2023
revised:
17
07
2023
medline:
2
10
2023
pubmed:
15
8
2023
entrez:
15
8
2023
Statut:
ppublish
Résumé
Gastric adenocarcinoma (GA) with enteroblastic differentiation (GAED) is an aggressive carcinoma histologically characterized by a glycogen-rich clear cytoplasm and fetal gut-like structures. GAED shows the expression of at least one of the following enteroblastic markers (EMs): glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), and α-fetoprotein (AFP). Despite the absence of clear cytoplasm, we often encounter GA with EMs expression (GA with EM); however, the clinicopathological characteristics of GA with EM remain unclear. Immunohistochemical (IHC) expression of three EMs (AFP, GPC3, and SALL4) was examined on tissue microarray. According to the status of the clear cytoplasm of tumor cells, GAs showing IHC expression of EMs were classified as either GAED or GA with EM, and this analysis categorized 688 GAs into 94 GAEDs (13.7%), 58 GAs with EM (8.4%), and 536 conventional GAs (CGAs). Both GAED and GA with EM showed frequent lymphovascular invasion, lymph node metastasis, and liver metastasis compared to CGA. However, a higher frequency of venous invasion, but not of lymphatic invasion, was noted for GAED in comparison to CGA. GAED and GA with EM showed similar overall survival. GAED had significantly poorer prognosis than CGA; however, not for GA with EM. Furthermore, GA showing EM expression had a worse prognosis than CGA. Interestingly, GA showing EM-positive group was more aggressive than CGA group as they had frequent venous invasion and liver metastasis despite its smaller tumor size. GAED and GA with EM can be clinically classified as aggressive tumors but pathologically they seem to be slightly different.
Identifiants
pubmed: 37581693
doi: 10.1007/s00428-023-03623-5
pii: 10.1007/s00428-023-03623-5
doi:
Substances chimiques
alpha-Fetoproteins
0
Biomarkers, Tumor
0
GPC3 protein, human
0
Glypicans
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
405-414Subventions
Organisme : Japan Society for the Promotion of Science
ID : 21K06931
Organisme : Japan Society for the Promotion of Science
ID : 20K07415
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Matsunou H, Konishi F, Jalal RE, Yamamichi N, Mukawa A (1994) Alpha-fetoprotein-producing gastric carcinoma with enteroblastic differentiation. Cancer 73:534–540
doi: 10.1002/1097-0142(19940201)73:3<534::AID-CNCR2820730307>3.0.CO;2-X
pubmed: 7507794
Govender D, Ramdial PK, Clarke B, Chetty R (2004) Clear cell (glycogen-rich) gastric adenocarcinoma. Ann Diagn Pathol 8:69–73
doi: 10.1053/j.anndiagpath.2004.01.002
pubmed: 15060883
Ghotli ZA, Serra S, Chetty R (2007) Clear cell (glycogen rich) gastric adenocarcinoma: A distinct tubulo-papillary variant with a predilection for the cardia/gastro-oesophageal region. Pathology 39:466–469
doi: 10.1080/00313020701569972
pubmed: 17886094
Yamazawa S, Ushiku T, Shinozaki-Ushiku A et al (2017) Gastric cancer with primitive enterocyte phenotype: An aggressive subgroup of intestinal-type adenocarcinoma. Am J Surg Pathol 41:989–997
doi: 10.1097/PAS.0000000000000869
pubmed: 28505005
Carneiro F, Fukayama M, Grabsch HI, Yasui W (2019) Gastric adenocarcinoma. WHO Classification of Tumours. 5th Edition. Digestive System Tumors p 85–95.
Chang YC, Nagasue N, Kohno H et al (1990) Clinicopathologic features and long-term results of alpha-fetoprotein-producing gastric cancer. Am J Gastroenterol 85:1480–1485
pubmed: 1700600
Chang YC, Nagasue N, Abe S, Taniura H, Kumar DD, Nakamura T (1992) Comparison between the clinicopathologic features of afp-positive and afp-negative gastric cancers. Am J Gastroenterol 87:321–325
pubmed: 1371637
Ishigami S, Natsugoe S, Nakashima H et al (2006) Biological aggressiveness of alpha-fetoprotein (afp)-positive gastric cancer. Hepatogastroenterology 53:338–341
pubmed: 16795967
Inoue M, Sano T, Kuchiba A, Taniguchi H, Fukagawa T, Katai H (2010) Long-term results of gastrectomy for alpha-fetoprotein-producing gastric cancer. Br J Surg 97:1056–1061
doi: 10.1002/bjs.7081
pubmed: 20632272
Akazawa Y, Saito T, Hayashi T et al (2018) Next-generation sequencing analysis for gastric adenocarcinoma with enteroblastic differentiation: Emphasis on the relationship with hepatoid adenocarcinoma. Hum Pathol 78:79–88
doi: 10.1016/j.humpath.2018.04.022
pubmed: 29751042
Ushiku T, Uozaki H, Shinozaki A et al (2009) Glypican 3-expressing gastric carcinoma: Distinct subgroup unifying hepatoid, clear-cell, and alpha-fetoprotein-producing gastric carcinomas. Cancer Sci 100:626–632
doi: 10.1111/j.1349-7006.2009.01108.x
pubmed: 19243386
Ushiku T, Shinozaki A, Shibahara J et al (2010) Sall4 represents fetal gut differentiation of gastric cancer, and is diagnostically useful in distinguishing hepatoid gastric carcinoma from hepatocellular carcinoma. Am J Surg Pathol 34:533–540
doi: 10.1097/PAS.0b013e3181d1dcdd
pubmed: 20182341
Ikeda H, Sato Y, Yoneda N et al (2012) Α-fetoprotein-producing gastric carcinoma and combined hepatocellular and cholangiocarcinoma show similar morphology but different histogenesis with respect to sall4 expression. Hum Pathol 43:1955–1963
doi: 10.1016/j.humpath.2011.11.022
pubmed: 22516245
Kono K, Amemiya H, Sekikawa T et al (2002) Clinicopathologic features of gastric cancers producing alpha-Fetoprotein. Dig Surg 19:359–365
doi: 10.1159/000065838
pubmed: 12435906
Liu X, Cheng Y, Sheng W et al (2010) Clinicopathologic features and prognostic factors in alpha-fetoprotein-producing gastric cancers: Analysis of 104 cases. J Surg Oncol 102:249–255
doi: 10.1002/jso.21624
pubmed: 20740583
He L, Ye F, Qu L et al (2016) Protein profiling of alpha-fetoprotein producing gastric adenocarcinoma. Oncotarget 7:28448–28459
doi: 10.18632/oncotarget.8571
pubmed: 27057629
pmcid: 5053738
Lu J, Jin M, Zhou X, Chen X, Shao Y, Jiang X (2022) Clinicopathological and molecular characteristics of the alpha-fetoprotein-producing gastric cancer: Emphasis on two major subtypes. APMIS 130:169–180
doi: 10.1111/apm.13196
pubmed: 34862662
Murakami T, Yao T, Mitomi H et al (2016) Clinicopathologic and immunohistochemical characteristics of gastric adenocarcinoma with enteroblastic differentiation: A study of 29 cases. Gastric Cancer 19:498–507
doi: 10.1007/s10120-015-0497-9
pubmed: 25893262
Kinjo T, Taniguchi H, Kushima R et al (2012) Histologic and immunohistochemical analyses of α-fetoprotein–producing cancer of the stomach. Am J Surg Pathol 36:56–65
doi: 10.1097/PAS.0b013e31823aafec
pubmed: 22173117
Matsumoto K, Ueyama H, Matsumoto K et al (2016) Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation. World J Gastroenterol 22:8203–8210
doi: 10.3748/wjg.v22.i36.8203
pubmed: 27688662
pmcid: 5037089
Kuroda N, Yorita K (2018) Clinicopathologic study of 10 cases of gastric adenocarcinoma with hepatoid or enteroblastic differentiation. Pol J Pathol 69:128–135
doi: 10.5114/pjp.2018.76696
pubmed: 30351859
Fujimoto M, Matsuzaki I, Nishino M et al (2018) Her2 is frequently overexpressed in hepatoid adenocarcinoma and gastric carcinoma with enteroblastic differentiation: A comparison of 35 cases to 334 gastric carcinomas of other histological types. J Clin Pathol 71:600–607
doi: 10.1136/jclinpath-2017-204928
pubmed: 29305518
Yatagai N, Saito T, Akazawa Y et al (2019) Tp53 inactivation and expression of methylation-associated proteins in gastric adenocarcinoma with enteroblastic differentiation. Virchows Arch 474:315–324
doi: 10.1007/s00428-018-2508-9
pubmed: 30554333
Yatagai N, Saito T, Akazawa Y et al (2019) Frequent loss of heterozygosity of smad4 locus and prognostic impacts of smad4 immunohistochemistry in gastric adenocarcinoma with enteroblastic differentiation. Hum Pathol 88:18–26
doi: 10.1016/j.humpath.2019.03.005
pubmed: 30946932
Yamashiro Y, Saito T, Hayashi T et al (2020) Molecular and clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation. Histopathology 77:492–502
doi: 10.1111/his.14158
pubmed: 32438490
Fang C, Wang W, Deng JY et al (2018) Proposal and validation of a modified staging system to improve the prognosis predictive performance of the 8th ajcc/uicc ptnm staging system for gastric adenocarcinoma: A multicenter study with external validation. Cancer Commun (Lond) 38:67
pubmed: 30454049
Kanda Y (2013) Investigation of the freely available easy-to-use software “ezr” for medical statistics. Bone Marrow Transplant 48:452–458
doi: 10.1038/bmt.2012.244
pubmed: 23208313
Miettinen M, Wang Z, McCue PA et al (2014) Sall4 expression in germ cell and non-germ cell tumors: A systematic immunohistochemical study of 3215 cases. Am J Surg Pathol 38:410–420
doi: 10.1097/PAS.0000000000000116
pubmed: 24525512
pmcid: 4041084
Kilic E, Tennstedt P, Högner A et al (2016) The zinc-finger transcription factor sall4 is frequently expressed in human cancers: Association with clinical outcome in squamous cell carcinoma but not in adenocarcinoma of the esophagus. Virchows Arch 468:483–492
doi: 10.1007/s00428-016-1908-y
pubmed: 26818834
Nicolè L, Sanavia T, Veronese N et al (2017) Oncofetal gene sall4 and prognosis in cancer: A systematic review with meta-analysis. Oncotarget 8:22968–22979
doi: 10.18632/oncotarget.14952
pubmed: 28160555
pmcid: 5410278
Adachi Y, Tsuchihashi J, Shiraishi N, Yasuda K, Etoh T, Kitano S (2003) Afp-producing gastric carcinoma: Multivariate analysis of prognostic factors in 270 patients. Oncology 65:95–101
doi: 10.1159/000072332
pubmed: 12931013
Zhan Z, Chen B, Yu J et al (2022) Elevated serum alpha-fetoprotein is a significant prognostic factor for patients with gastric cancer: Results based on a large-scale retrospective study. Front Oncol 12:901061
doi: 10.3389/fonc.2022.901061
pubmed: 35847953
pmcid: 9277009
Bang YJ, Van Cutsem E, Feyereislova A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of her2-positive advanced gastric or gastro-oesophageal junction cancer (toga): A phase 3, open-label, randomised controlled trial. Lancet 376:687–697
doi: 10.1016/S0140-6736(10)61121-X
pubmed: 20728210
Boku N, Ryu MH, Kato K et al (2019) Safety and efficacy of nivolumab in combination with s-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: Interim results of a randomized, phase ii trial (attraction-4). Ann Oncol 30:250–258
doi: 10.1093/annonc/mdy540
pubmed: 30566590
Shitara K, Bang YJ, Iwasa S et al (2020) Trastuzumab deruxtecan in previously treated her2-positive gastric cancer. N Engl J Med 382:2419–2430
doi: 10.1056/NEJMoa2004413
pubmed: 32469182
Janjigian YY, Shitara K, Moehler M et al (2021) First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (checkmate 649): A randomised, open-label, phase 3 trial. Lancet 398:27–40
doi: 10.1016/S0140-6736(21)00797-2
pubmed: 34102137
pmcid: 8436782
Shitara K, Ajani JA, Moehler M et al (2022) Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature 603:942–948
doi: 10.1038/s41586-022-04508-4
pubmed: 35322232
pmcid: 8967713