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08.01.2022 | Original Article

Tumor progression by epithelial-mesenchymal transition in ARID1A- and SMARCA4-aberrant solid-type poorly differentiated gastric adenocarcinoma

verfasst von: Taisuke Sasaki, Kenichi Kohashi, Shinichiro Kawatoko, Eikichi Ihara, Eiji Oki, Masafumi Nakamura, Yoshihiro Ogawa, Yoshinao Oda

Erschienen in: Virchows Archiv | Ausgabe 5/2022

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Abstract

Solid-type poorly differentiated adenocarcinoma (PDA) of the stomach is frequently associated with microsatellite instability (MSI) and aberrations of the SWI/SNF chromatin remodeling complex. Previous studies showed that aberrant ARID1A and SMARCA4 expression induces mesenchymal transition. We analyzed 51 primary-site cases and 209 metastatic lymph nodes among solid-type PDA for the expression of SWI/SNF complex subunits (ARID1A, SMARCA4, SMARCB1, SMARCC2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, β-catenin, Snail). We also analyzed 40 cases of non-solid-type PDA as a stage-matched control group. Aberrant expression of ARID1A (39%) and SMARCA4 (49%) was more common in solid-type PDA than in non-solid-type PDA (ARID1A, P = 0.0049; SMARCA4, P < 0.0001). The group of solid-type PDA with aberrant ARID1A showed significantly longer overall and progression-free survival than the corresponding ARID1A-retained group (P = 0.0405 and P = 0.0296, respectively). Aberrant expression of EMT factors inducing mesenchymal transition in the groups with solid-type PDA at the primary site or metastatic lymph nodes with aberrant ARID1A was less common than in the corresponding groups with retained ARID1A (E-cadherin, primary site P = 0.0341, lymph node P < 0.0001; β-catenin, primary site P = 0.0293, lymph node P = 0.0010; Snail, primary site P = 0.0169, lymph node P = 0.0828). Furthermore, N3 of the TNM classification was more frequently observed in the group with solid-type PDA with retained ARID1A than in the corresponding ARID1A-aberrant group (P = 0.0288). Mesenchymal transition was not induced in the ARID1A-aberrant group, in which patients had favorable prognosis, and preserved epithelial characteristics in EMT may play an important role in low tumor aggressiveness of solid-type PDA.

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Tsuruta S, Kohashi K, Yamada Y, Fujiwara M, Koga Y, Ihara E, Ogawa Y, Oki E, Nakamura M, Oda Y (2020) Solid-type poorly differentiated adenocarcinoma of the stomach: deficiency of mismatch repair and SWI/SNF complex. Cancer Sci 111:1008–1019. https://doi.org/10.1111/cas.14301CrossRefPubMedPubMedCentral

Kunisaki C, Akiyama H, Nomura M, Matsuda G, Otsuka Y, Ono HA, Nagahori Y, Takahashi M, Kito F, Shimada H (2006) Clinicopathological properties of poorly-differentiated adenocarcinoma of the stomach: comparison of solid- and non-solid-types. Anticancer Res 26:639–646PubMed

Hirai H, Yoshizawa T, Morohashi S, Haga T, Wu YY, Ota R, Takatsuna M, Akasaka H, Hakamada K, Kijima H (2016) Clinicopathological significance of gastric poorly differentiated medullary carcinoma. Biomed Res-Tokyo 37:77–84. https://doi.org/10.2220/biomedres.37.77CrossRef

Otsuji E, Kuriu Y, Ichikawa D, Ochiai T, Okamoto K, Hagiwara A, Yamagishi H (2004) Clinicopathologic and prognostic characterization of poorly differentiated medullary-type gastric adenocarcinoma. World J Surg 28:862–865. https://doi.org/10.1007/s00268-004-7481-6CrossRefPubMed

Lu BJ, Lai M, Cheng L, Xu JY, Huang Q (2004) Gastric medullary carcinoma, a distinct entity associated with microsatellite instability-H, prominent intraepithelial lymphocytes and improved prognosis. Histopathology 45:485–492. https://doi.org/10.1111/j.1365-2559.2004.01998.xCrossRefPubMed

Carneiro F, Fukuyama M, Grabsch HI, Yasui, W, et al (2019) Gastric adenocarcinoma. In WHO Classification of Tumors Editorial Board, ed. WHO Classification of Tumors 5th edition: Digestive System. Lyon, France:85–90

Japanese Gastric Cancer A (2011) Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer 14:101–112. https://doi.org/10.1007/s10120-011-0041-5

Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–209. https://doi.org/10.1038/nature13480CrossRef

Arai T, Matsuda Y, Aida J, Takubo K, Ishiwata T (2019) Solid-type poorly differentiated adenocarcinoma of the stomach: clinicopathological and molecular characteristics and histogenesis. Gastric Cancer 22:314–322. https://doi.org/10.1007/s10120-018-0862-6CrossRefPubMed

10.

Arai T, Sakurai U, Sawabe M, Honma N, Aida J, Ushio Y, Kanazawa N, Kuroiwa K, Takubo K (2013) Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach. Gastric Cancer 16:505–512. https://doi.org/10.1007/s10120-012-0226-6CrossRefPubMed

11.

Yan HB, Wang XF, Zhang Q, Tang ZQ, Jiang YH, Fan HZ, Sun YH, Yang PY, Liu F (2014) Reduced expression of the chromatin remodeling gene ARID1A enhances gastric cancer cell migration and invasion via downregulation of E-cadherin transcription. Carcinogenesis 35:867–876. https://doi.org/10.1093/carcin/bgt398CrossRefPubMed

12.

Banine F, Bartlett C, Gunawardena R, Muchardt C, Yaniv M, Knudsen ES, Weissman BE, Sherman LS (2005) SWI/SNF chromatin-remodeling factors induce changes in DNA methylation to promote transcriptional activation. Cancer Res 65:3542–3547. https://doi.org/10.1158/0008-5472.Can-04-3554CrossRefPubMed

13.

Tsuruta S, Ohishi Y, Fujiwara M, Ihara E, Ogawa Y, Oki E, Nakamura M, Oda Y (2019) Gastric hepatoid adenocarcinomas are a genetically heterogenous group; most tumors show chromosomal instability, but MSI tumors do exist. Hum Pathol 88:27–38. https://doi.org/10.1016/j.humpath.2019.03.006CrossRefPubMed

14.

Choi YY, An JY, Katai H, Seto Y, Fukagawa T, Okumura Y, Kim DW, Kim HI, Cheong JH, Hyung WJ, Noh SH (2016) A lymph node staging system for gastric cancer: a hybrid type based on topographic and numeric systems. PLoS ONE 11:e0149555. https://doi.org/10.1371/journal.pone.0149555CrossRefPubMedPubMedCentral

15.

Choi YY, An JY, Guner A, Kang DR, Cho I, Kwon IG, Shin HB, Hyung WJ, Noh SH (2016) Skip lymph node metastasis in gastric cancer: is it skipping or skipped? Gastric Cancer 19:206–215. https://doi.org/10.1007/s10120-015-0472-5CrossRefPubMed

16.

Kinoshita F, Kohashi K, Sugimoto M, Takamatsu D, Kiyozawa D, Eto M, Oda Y (2020) The SWI/SNF chromatin-remodeling complex status in renal cell carcinomas with sarcomatoid or rhabdoid features. Virchows Arch 477:651–660. https://doi.org/10.1007/s00428-020-02839-zCrossRefPubMed

17.

Mao TL, Ardighieri L, Ayhan A, Kuo KT, Wu CH, Wang TL, Shih Ie M (2013) Loss of ARID1A expression correlates with stages of tumor progression in uterine endometrioid carcinoma. Am J Surg Pathol 37:1342–1348. https://doi.org/10.1097/PAS.0b013e3182889dc3CrossRefPubMedPubMedCentral

18.

Takahashi S, Kohashi K, Yamamoto H, Hirahashi M, Kumagai R, Takizawa N, Nakamura K, Maehara Y, Tanaka M, Takayanagi R, Oda Y (2015) Expression of adhesion molecules and epithelial-mesenchymal transition factors in medullary carcinoma of the colorectum. Hum Pathol 46:1257–1266. https://doi.org/10.1016/j.humpath.2015.05.023CrossRefPubMed

19.

He F, Li J, Xu J, Zhang S, Xu Y, Zhao W, Yin Z, Wang X (2015) Decreased expression of ARID1A associates with poor prognosis and promotes metastases of hepatocellular carcinoma. J Exp Clin Cancer Res 34:47. https://doi.org/10.1186/s13046-015-0164-3CrossRefPubMedPubMedCentral

20.

Abe H, Maeda D, Hino R, Otake Y, Isogai M, Ushiku AS, Matsusaka K, Kunita A, Ushiku T, Uozaki H, Tateishi Y, Hishima T, Iwasaki Y, Ishikawa S, Fukayama M (2012) ARID1A expression loss in gastric cancer: pathway-dependent roles with and without Epstein-Barr virus infection and microsatellite instability. Virchows Arch 461:367–377. https://doi.org/10.1007/s00428-012-1303-2CrossRefPubMed

21.

Huang SC, Ng KF, Yeh TS, Cheng CT, Chen MC, Chao YC, Chuang HC, Liu YJ, Chen TC (2020) The clinicopathological and molecular analysis of gastric cancer with altered SMARCA4 expression. Histopathology 77:250–261. https://doi.org/10.1111/his.14117CrossRefPubMed

22.

Takeshima H, Niwa T, Takahashi T, Wakabayashi M, Yamashita S, Ando T, Inagawa Y, Taniguchi H, Katai H, Sugiyama T, Kiyono T, Ushijima T (2015) Frequent involvement of chromatin remodeler alterations in gastric field cancerization. Cancer Lett 357:328–338. https://doi.org/10.1016/j.canlet.2014.11.038CrossRefPubMed

23.

Medina PP, Carretero J, Fraga MF, Esteller M, Sidransky D, Sanchez-Cespedes M (2004) Genetic and epigenetic screening for gene alterations of the chromatin-remodeling factor, SMARCA4/BRG1, in lung tumors. Genes Chromosom Cancer 41:170–177. https://doi.org/10.1002/gcc.20068CrossRefPubMed

24.

Coira IF, Rufino-Palomares EE, Romero OA, Peinado P, Metheetrairut C, Boyero-Corral L, Carretero J, Farez-Vidal E, Cuadros M, Reyes-Zurita FJ, Lupianez JA, Sanchez-Cespedes M, Slack FJ, Medina PP (2015) Expression inactivation of SMARCA4 by microRNAs in lung tumors. Hum Mol Genet 24:1400–1409. https://doi.org/10.1093/hmg/ddu554CrossRefPubMed

25.

Lichner Z, Scorilas A, White NM, Girgis AH, Rotstein L, Wiegand KC, Latif A, Chow C, Huntsman D, Yousef GM (2013) The chromatin remodeling gene ARID1A is a new prognostic marker in clear cell renal cell carcinoma. Am J Pathol 182:1163–1170. https://doi.org/10.1016/j.ajpath.2013.01.007CrossRefPubMed

26.

Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, Chan TL, Kan Z, Chan AS, Tsui WY, Lee SP, Ho SL, Chan AK, Cheng GH, Roberts PC, Rejto PA, Gibson NW, Pocalyko DJ, Mao M, Xu J, Leung SY (2011) Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet 43:1219–1223. https://doi.org/10.1038/ng.982CrossRefPubMed

27.

Lowenthal BM, Nason KS, Pennathur A, Luketich JD, Pai RK, Davison JM, Ma C (2019) Loss of ARID1A expression is associated with DNA mismatch repair protein deficiency and favorable prognosis in advanced stage surgically resected esophageal adenocarcinoma. Hum Pathol 94:1–10. https://doi.org/10.1016/j.humpath.2019.09.004CrossRefPubMed

28.

Gabbert HE, Meier S, Gerharz CD, Hommel G (1991) Incidence and prognostic-significance of vascular invasion in 529 gastric-cancer patients. Int J Cancer 49:203–207. https://doi.org/10.1002/ijc.2910490210CrossRefPubMed

29.

Maehara Y, Oshiro T, Baba H, Ohno S, Kohnoe S, Sugimachi K (1995) Lymphatic invasion and potential for tumor-growth and metastasis in patients with gastric-cancer surgery 117:380–385. https://doi.org/10.1016/S0039-6060(05)80056-XCrossRefPubMed

30.

Wang H, Bierie B, Li AG, Pathania S, Toomire K, Dimitrov SD, Liu B, Gelman R, Giobbie-Hurder A, Feunteun J, Polyak K, Livingston DM (2016) BRCA1/FANCD2/BRG1-driven DNA repair stabilizes the differentiation state of human mammary epithelial cells. Mol Cell 63:277–292. https://doi.org/10.1016/j.molcel.2016.05.038CrossRefPubMedPubMedCentral

31.

Tomihara H, Carbone F, Perelli L, Huang JK, Soeung M, Rose JL, Robinson FS, LissanuDeribe Y, Feng N, Takeda M, Inoue A, Poggetto ED, Deem AK, Maitra A, Msaouel P, Tannir NM, Draetta GF, Viale A, Heffernan TP, Bristow CA, Carugo A, Genovese G (2021) Loss of ARID1A promotes epithelial-mesenchymal transition and sensitizes pancreatic tumors to proteotoxic stress. Cancer Res 81:332–343. https://doi.org/10.1158/0008-5472.CAN-19-3922CrossRefPubMed

32.

Ye J, Zhou Y, Weiser MR, Gonen M, Zhang L, Samdani T, Bacares R, DeLair D, Ivelja S, Vakiani E, Klimstra DS, Soslow RA, Shia J (2014) Immunohistochemical detection of ARID1A in colorectal carcinoma: loss of staining is associated with sporadic microsatellite unstable tumors with medullary histology and high TNM stage. Hum Pathol 45:2430–2436. https://doi.org/10.1016/j.humpath.2014.08.007CrossRefPubMed

33.

Pyo JS, Sohn JH, Kang G (2016) Medullary carcinoma in the colorectum: a systematic review and meta-analysis. Hum Pathol 53:91–96. https://doi.org/10.1016/j.humpath.2016.02.018CrossRefPubMed

34.

Matsubara D, Kishaba Y, Ishikawa S, Sakatani T, Oguni S, Tamura T, Hoshino H, Sugiyama Y, Endo S, Murakami Y, Aburatani H, Fukayama M, Niki T (2013) Lung cancer with loss of BRG1/BRM, shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features. Cancer Sci 104:266–273. https://doi.org/10.1111/cas.12065CrossRefPubMedPubMedCentral

Titel: Tumor progression by epithelial-mesenchymal transition in ARID1A- and SMARCA4-aberrant solid-type poorly differentiated gastric adenocarcinoma
verfasst von: Taisuke Sasaki
Kenichi Kohashi
Shinichiro Kawatoko
Eikichi Ihara
Eiji Oki
Masafumi Nakamura
Yoshihiro Ogawa
Yoshinao Oda
Publikationsdatum: 08.01.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: Virchows Archiv / Ausgabe 5/2022
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-021-03261-9

Neu im Fachgebiet Pathologie

Open Access 15.04.2024 | Biomarker | Schwerpunkt: Next Generation Pathology

Springer Medizin

Tumor progression by epithelial-mesenchymal transition in ARID1A- and SMARCA4-aberrant solid-type poorly differentiated gastric adenocarcinoma

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

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