Top

Published in:

Open Access 01-09-2020 | Gastric Cancer | Review Article

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer

Authors: K. G. P. Kerckhoffs, D. H. W. Liu, L. Saragoni, R. S. van der Post, R. Langer, M. Bencivenga, M. Iglesias, G. Gallo, L. C. Hewitt, G. E. Fazzi, A. M. Vos, F. Renaud, T. Yoshikawa, T. Oshima, A. Tomezzoli, G. de Manzoni, T. Arai, R. Kushima, F. Carneiro, H. I. Grabsch

Published in: Gastric Cancer | Issue 5/2020

Abstract

Background

The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin–eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome.

Methods

We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed.

Results

Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome.

In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients.

Conclusions

This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Available only for authorised users

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E386. https://doi.org/10.1002/ijc.29210.CrossRef

Wu H, Rusiecki JA, Zhu K, Potter J, Devesa SS. Stomach carcinoma incidence patterns in the United States by histologic type and anatomic site. Cancer Epidemiol Biomarkers Prev. 2009;18(7):1945–52. https://doi.org/10.1158/1055-9965.PubMedPubMedCentralCrossRef

Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States, 1973–2000: increase in the signet ring cell type. Arch Pathol Lab Med. 2004;128(7):765–70.PubMed

Kim JP, Kim SC, Yang HK. Prognostic significance of signet ring cell carcinoma of the stomach. Surg Oncol. 1994;3(4):221–7.PubMedCrossRef

Kunisaki C, Takahashi M, Nagahori Y, Fukushima T, Makino H, Takagawa R, et al. Risk factors for lymph node metastasis in histologically poorly differentiated type early gastric cancer. Endoscopy. 2009;41(6):498–503. https://doi.org/10.1055/s-0029-1214758.PubMedCrossRef

Maehara Y, Sakaguchi Y, Moriguchi S, Orita H, Korenaga D, Kohnoe S, et al. Signet ring cell carcinoma of the stomach. Cancer. 1992;69(7):1645–50.PubMedCrossRef

Taghavi S, Jayarajan SN, Davey A, Willis AI. Prognostic significance of signet ring gastric cancer. J Clin Oncol. 2012;30(28):3493–8. https://doi.org/10.1200/jco.2012.42.6635.PubMedPubMedCentralCrossRef

Zhang M, Zhu G, Zhang H, Gao H, Xue Y. Clinicopathologic features of gastric carcinoma with signet ring cell histology. J Gastrointest Surg. 2010;14(4):601–6. https://doi.org/10.1007/s11605-009-1127-9.PubMedCrossRef

Li C, Kim S, Lai JF, Hyung WJ, Choi WH, Choi SH, et al. Advanced gastric carcinoma with signet ring cell histology. Oncology. 2007;72(1–2):64–8. https://doi.org/10.1159/000111096.PubMedCrossRef

10.

Piessen G, Messager M, Leteurtre E, Jean-Pierre T, Mariette C. Signet ring cell histology is an independent predictor of poor prognosis in gastric adenocarcinoma regardless of tumoral clinical presentation. Ann Surg. 2009;250(6):878–87. https://doi.org/10.1097/SLA.0b013e3181b21c7b.PubMedCrossRef

11.

Bamboat ZM, Tang LH, Vinuela E, Kuk D, Gonen M, Shah MA, et al. Stage-stratified prognosis of signet ring cell histology in patients undergoing curative resection for gastric adenocarcinoma. Ann Surg Oncol. 2014;21(5):1678–85. https://doi.org/10.1245/s10434-013-3466-8.PubMedCrossRef

12.

Chon HJ, Hyung WJ, Kim C, Park S, Kim JH, Park CH, et al. Differential prognostic implications of gastric signet ring cell carcinoma: stage adjusted analysis from a single high-volume center in asia. Ann Surg. 2017;265(5):946–53. https://doi.org/10.1097/sla.0000000000001793.PubMedPubMedCentralCrossRef

13.

Ha TK, An JY, Youn HK, Noh JH, Sohn TS, Kim S. Indication for endoscopic mucosal resection in early signet ring cell gastric cancer. Ann Surg Oncol. 2008;15(2):508–13. https://doi.org/10.1245/s10434-007-9660-9.PubMedCrossRef

14.

Hyung WJ, Noh SH, Lee JH, Huh JJ, Lah KH, Choi SH, et al. Early gastric carcinoma with signet ring cell histology. Cancer. 2002;94(1):78–83.PubMedCrossRef

15.

Kim DY, Park YK, Joo JK, Ryu SY, Kim YJ, Kim SK, et al. Clinicopathological characteristics of signet ring cell carcinoma of the stomach. ANZ J Surg. 2004;74(12):1060–4. https://doi.org/10.1111/j.1445-1433.2004.03268.x.PubMedCrossRef

16.

Otsuji E, Yamaguchi T, Sawai K, Takahashi T. Characterization of signet ring cell carcinoma of the stomach. J Surg Oncol. 1998;67(4):216–20.PubMedCrossRef

17.

Yokota T, Kunii Y, Teshima S, Yamada Y, Saito T, Kikuchi S, et al. Signet ring cell carcinoma of the stomach: a clinicopathological comparison with the other histological types. Tohoku J Exp Med. 1998;186(2):121–30.PubMedCrossRef

18.

Patel VR, Hofstetter WL, Correa AM, Agarwal A, Rashid A, Bhutani MS, et al. Signet ring cells in esophageal adenocarcinoma predict poor response to preoperative chemoradiation. Ann Thorac Surg. 2014;98(3):1064–71. https://doi.org/10.1016/j.athoracsur.2014.04.099.PubMedCrossRef

19.

Charalampakis N, Nogueras Gonzalez GM, Elimova E, Wadhwa R, Shiozaki H, Shimodaira Y, et al. The proportion of signet ring cell component in patients with localized gastric adenocarcinoma correlates with the degree of response to pre-operative chemoradiation. Oncology. 2016;90(5):239–47. https://doi.org/10.1159/000443506.PubMedPubMedCentralCrossRef

20.

Chirieac LR, Swisher SG, Correa AM, Ajani JA, Komaki RR, Rashid A, et al. Signet-ring cell or mucinous histology after preoperative chemoradiation and survival in patients with esophageal or esophagogastric junction adenocarcinoma. Clin Can Res. 2005;11(6):2229–36. https://doi.org/10.1158/1078-0432.Ccr-04-1840.CrossRef

21.

Heger U, Sisic L, Nienhuser H, Blank S, Hinz U, Haag GM, et al. Neoadjuvant therapy improves outcomes in locally advanced signet-ring-cell containing esophagogastric adenocarcinomas. Ann Surg Oncol. 2018;25(8):2418–27. https://doi.org/10.1245/s10434-018-6541-3.PubMedCrossRef

22.

Heger U, Blank S, Wiecha C, Langer R, Weichert W, Lordick F, et al. Is preoperative chemotherapy followed by surgery the appropriate treatment for signet ring cell containing adenocarcinomas of the esophagogastric junction and stomach? Ann Surg Oncol. 2014;21(5):1739–48. https://doi.org/10.1245/s10434-013-3462-z.PubMedCrossRef

23.

van Hootegem SJM, Smithers BM, Gotley DC, Brosda S, Thomson IG, Thomas JM, et al. The impact of signet ring cell differentiation on outcome in patients with esophageal and gastroesophageal junction adenocarcinoma. Ann Surg Oncol. 2019;26(8):2375–84. https://doi.org/10.1245/s10434-019-07322-x.PubMedPubMedCentralCrossRef

24.

Messager M, Lefevre JH, Pichot-Delahaye V, Souadka A, Piessen G, Mariette C, et al. The impact of perioperative chemotherapy on survival in patients with gastric signet ring cell adenocarcinoma: a multicenter comparative study. Ann Surg. 2011;254(5):684–93. https://doi.org/10.1097/SLA.0b013e3182352647.PubMedCrossRef

25.

Mariette C, Carneiro F, Grabsch HI, van der Post RS, Allum W, de Manzoni G, et al. Consensus on the pathological definition and classification of poorly cohesive gastric carcinoma. Gastric Cancer. 2019;22(1):1–9. https://doi.org/10.1007/s10120-018-0868-0.PubMedCrossRef

26.

Lauren 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. https://doi.org/10.1111/apm.1965.64.1.31.PubMedCrossRef

27.

Oota K, Sobin LH. Histological typing of gastric and oesophageal tumours. 1st ed. WHO International histological classification of tumours, No 18. Geneva. 1977.

28.

Bosman FT, Carneiro F, Hruban RH, Theise ND (eds). WHO classification of tumours of the digestive system. 4th ed. 2010.

29.

Watanabe H, Jass JR, Sobin LH (eds). Histological typing of oesophageal and gastric tumours. 2nd ed. WHO: International histological classification of tumours. Springer-Verlag, Berlin Heidelberg; 1990.CrossRef

30.

Hamilton SR, Aaltonen LA, (eds). Pathology and Genetics of tumours of the digestive system. 3rd ed. WHO classification of tumours: IARC press Lyon; 2000.

31.

WHO Classification of Tumours Editorial Board (eds). Digestive system tumours. 5th ed. Lyon: IARC Press; 2019.

32.

Hewitt LC, Inam IZ, Saito Y, Yoshikawa T, Quaas A, Hoelscher A, et al. Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study. Eur J Cancer 2018;94:104–14. https://doi.org/10.1016/j.ejca.2018.02.014.PubMedPubMedCentralCrossRef

33.

Bamba M, Sugihara H, Kushima R, Okada K, Tsukashita S, Horinouchi M, et al. Time-dependent expression of intestinal phenotype in signet ring cell carcinomas of the human stomach. Virchows Arch. 2001;438(1):49–56.PubMedCrossRef

34.

Tsukashita S, Kushima R, Bamba M, Nakamura E, Mukaisho K, Sugihara H, et al. Beta-catenin expression in intramucosal neoplastic lesions of the stomach. Comparative analysis of adenoma/dysplasia, adenocarcinoma and signet-ring cell carcinoma. Oncology. 2003;64(3):251–8. https://doi.org/10.1159/000069310.PubMedCrossRef

35.

Aihara R, Mochiki E, Kamiyama Y, Kamimura H, Asao T, Kuwano H. Mucin phenotypic expression in early signet ring cell carcinoma of the stomach: its relationship with the clinicopathologic factors. Dig Dis Sci. 2004;49(3):417–24.PubMedCrossRef

36.

Aihara R, Mochiki E, Nakabayashi T, Akazawa K, Asao T, Kuwano H. Clinical significance of mucin phenotype, beta-catenin and matrix metalloproteinase 7 in early undifferentiated gastric carcinoma. Br J Surg. 2005;92(4):454–62.PubMedCrossRef

37.

Ohkura Y, Kawamata H, Chibana Y, Ichikawa K, Fujii S, Tomita S, et al. Histopathological study of small (%3c2 cm) gastric carcinoma with signet-ring cell component: significance of the admixed glandular components. Int J Surg Pathol. 2005;13(2):197–203. https://doi.org/10.1177/106689690501300211.PubMedCrossRef

38.

Tian MM, Zhao AL, Li ZW, Li JY. Phenotypic classification of gastric signet ring cell carcinoma and its relationship with clinicopathologic parameters and prognosis. World J Gastroenterol. 2007;13(23):3189–98.PubMedPubMedCentralCrossRef

39.

Nakajima T, Uehara T, Maruyama Y, Iwaya M, Kobayashi Y, Ota H. Distribution of Lgr5-positive cancer cells in intramucosal gastric signet-ring cell carcinoma. Pathol Int. 2016;66(9):518–23. https://doi.org/10.1111/pin.12451.PubMedCrossRef

40.

Xiong ZF, Shi J, Fu ZH, Wan HP, Tu LX. Phenotypic classification of gastric signet ring cell carcinoma and its relationship with K-ras mutation. Genet Mol Res. 2017. https://doi.org/10.4238/gmr16029181.PubMedCrossRef

41.

Terada T. An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: II. Expression of MUC1, MUC2, MUC5AC, and MUC6 in normal mucosa and in 42 cases. Int J Clin Exp Pathol. 2013;6(4):613–21.

42.

Terada T. An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: III. Expressions of EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63 in normal mucosa and in 42 cases. Int J Clin Exper Pathol. 2013;6(4):630–8.

43.

Fujiyoshi Y, Eimoto T. Chromogranin A expression correlates with tumour cell type and prognosis in signet ring cell carcinoma of the stomach. Histopathology. 2008;52(3):305–13. https://doi.org/10.1111/j.1365-2559.2007.02950.x.PubMedCrossRef

44.

Bakkelund K, Fossmark R, Nordrum I, Waldum H. Signet ring cells in gastric carcinomas are derived from neuroendocrine cells. J Histochem Cytochem. 2006;54(6):615–21.PubMedCrossRef

45.

Santini D, Bazzocchi F, Mazzoleni G, Ricci M, Viti G, Marrano D et al (1987) Signet-ring cells in advanced gastric cancer. A clinical, pathological and histochemical study. Acta Pathol Microbiol Immunol Scand A 95(5):225–231

46.

Yamachika T, Inada K, Fujimitsu Y, Nakamura S, Yamamura Y, Kitou T, et al. Intestinalization of gastric signet ring cell carcinomas with progression. Virchows Arch. 1997;431(2):103–10.PubMedCrossRef

47.

Akyurek N, Akyol G, Dursun A, Yamac D, Gunel N. Expression of MUC1 and MUC2 mucins in gastric carcinomas: their relationship with clinicopathologic parameters and prognosis. Pathol Res Pract. 2002;198(10):665–74. https://doi.org/10.1078/0344-0338-00318.PubMedCrossRef

48.

Baldus SE, Zirbes TK, Engel S, Hanisch FG, Monig SP, Lorenzen J, et al. Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas. Int J Cancer. 1998;79(2):133–8.PubMedCrossRef

49.

Bartley AN, Rashid A, Fournier KF, Abraham SC. Neuroendocrine and mucinous differentiation in signet ring cell carcinoma of the stomach: evidence for a common cell of origin in composite tumors. Hum Pathol. 2011;42(10):1420–9. https://doi.org/10.1016/j.humpath.2010.12.008.PubMedCrossRef

50.

Kim YH, Park JH, Park CK, Kim JH, Lee SK, Lee YC, et al. Histologic purity of signet ring cell carcinoma is a favorable risk factor for lymph node metastasis in poorly cohesive, submucosa-invasive early gastric carcinoma. Gastric Cancer. 2017;20(4):583–90. https://doi.org/10.1007/s10120-016-0645-x.PubMedCrossRef

51.

Ilhan O, Han U, Onal B, Celik SY. Prognostic significance of MUC1, MUC2 and MUC5AC expressions in gastric carcinoma. Turk J Gastroenterol. 2010;21(4):345–52.PubMedCrossRef

52.

Chu PG, Weiss LM. Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon. Am J Clin Pathol. 2004;121(6):884–92. https://doi.org/10.1309/a09e-rymf-r64n-erdw.PubMedCrossRef

53.

Kubota K, Yamada S, Ito M, Nakamura W, Nagayo T. Cytoplasmic leucine naphthylamidase activity expressed in signet-ring cell carcinoma of the stomach. J Natl Cancer Inst. 1977;59(6):1599–604.PubMedCrossRef

54.

Akamatsu T, Katsuyama T. Histochemical demonstration of mucins in the intramucosal laminated structure of human gastric signet ring cell carcinoma and its relation to submucosal invasion. Histochem J. 1990;22(8):416–25.PubMedCrossRef

55.

Tatematsu M, Ichinose M, Miki K, Hasegawa R, Kato T, Ito N. Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry. Acta Pathol Jpn. 1990;40(7):494–504.

56.

Tatematsu M, Hasegawa R, Ogawa K, Kato T, Ichinose M, Miki K, et al. Histogenesis of human stomach cancers based on assessment of differentiation. J Clin Gastroenterol. 1992;14(Suppl 1):S1–7.PubMedCrossRef

57.

Takenoshita S, Hashizume T, Katoh R, Koitabashi H, Nagamachi Y. Mucin production and subsequent interstitial fibrosis in gastric-cancer with signet-ring cells. Oncol Rep. 1994;1(3):537–41.PubMed

58.

Nguyen MD, Plasil B, Wen P, Frankel WL. Mucin profiles in signet-ring cell carcinoma. Arch Pathol Lab Med. 2006;130(6):799–804. https://doi.org/10.1043/1543-2165(2006)130[799:Mpiscc]2.0.Co;2.PubMedCrossRef

59.

Sakamoto H, Yonezawa S, Utsunomiya T, Tanaka S, Kim YS, Sato E. Mucin antigen expression in gastric carcinomas of young and old adults. Hum Pathol. 1997;28(9):1056–65.PubMedCrossRef

60.

Fujimoto A, Ishikawa Y, Ishii T, Yamada A, Igarashi Y, Ohmoto Y, et al. Differences between gastric signet-ring cell carcinoma and poorly differentiated adenocarcinoma: a comparison of histopathologic features determined by mucin core protein and trefoil factor family peptide immunohistochemistry. Pathol Int. 2017;67(8):398–403. https://doi.org/10.1111/pin.12559.PubMedCrossRef

61.

Gurbuz Y, Kahlke V, Kloppel G. How do gastric carcinoma classification systems relate to mucin expression patterns? An immunohistochemical analysis in a series of advanced gastric carcinomas. Virchows Arch. 2002;440(5):505–11. https://doi.org/10.1007/s00428-002-0620-2.PubMedCrossRef

62.

Zhang HK, Zhang QM, Zhao TH, Li YY, Yi YF. Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance. World J Gastroenterol. 2004;10(20):3044–7.PubMedPubMedCentralCrossRef

63.

Yonezawa S, Kitajima S, Higashi M, Osako M, Horinouchi M, Yokoyama S, et al. A novel anti-MUC1 antibody against the MUC1 cytoplasmic tail domain: use in sensitive identification of poorly differentiated cells in adenocarcinoma of the stomach. Gastric Cancer. 2012;15(4):370–81. https://doi.org/10.1007/s10120-011-0125-2.PubMedPubMedCentralCrossRef

64.

Seki T, Ito T, Kawachi H, Sekine M, Funata N, Takizawa T. Relationship between mucin expression of gastric intramucosal signet ring cell carcinoma and its background mucosa. J Med Dent Sci. 2009;56(1):25–35.PubMed

65.

Chiaravalli AM, Klersy C, Tava F, Manca R, Fiocca R, Capella C, et al. Lower- and higher-grade subtypes of diffuse gastric cancer. Hum Pathol. 2009;40(11):1591–9. https://doi.org/10.1016/j.humpath.2009.04.004.PubMedCrossRef

66.

Yoshikawa A, Inada Ki KI, Yamachika T, Shimizu N, Kaminishi M, Tatematsu M. Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression. Gastric Cancer. 1998;1(2):134–41. https://doi.org/10.1007/s101200050007.PubMedCrossRef

67.

Yamada T, Yoshikawa T, Taguri M, Hayashi T, Aoyama T, Sue-Ling HM, et al. The survival difference between gastric cancer patients from the UK and Japan remains after weighted propensity score analysis considering all background factors. Gastric Cancer. 2016;19(2):479–89. https://doi.org/10.1007/s10120-015-0480-5.PubMedCrossRef

Title: Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer
Authors: K. G. P. Kerckhoffs
D. H. W. Liu
L. Saragoni
R. S. van der Post
R. Langer
M. Bencivenga
M. Iglesias
G. Gallo
L. C. Hewitt
G. E. Fazzi
A. M. Vos
F. Renaud
T. Yoshikawa
T. Oshima
A. Tomezzoli
G. de Manzoni
T. Arai
R. Kushima
F. Carneiro
H. I. Grabsch
Publication date: 01-09-2020
Publisher: Springer Singapore
Keywords: Gastric Cancer
Gastric Cancer
Published in: Gastric Cancer / Issue 5/2020
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI: https://doi.org/10.1007/s10120-020-01086-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2020

Metabolomic profiling of gastric cancer tissues identified potential biomarkers for predicting peritoneal recurrence

Therapeutic value of splenectomy to dissect splenic hilar lymph nodes for type 4 gastric cancer involving the greater curvature, compared with other types

Brain metastases in patients with upper gastrointestinal cancer is associated with proximally located adenocarcinoma and lymph node metastases

Impact of endoscopic resection on the choice of surgical procedure in patients with additional laparoscopic gastrectomy

A panel of intestinal differentiation markers (CDX2, GPA33, and LI-cadherin) identifies gastric cancer patients with favourable prognosis

Epstein–Barr virus-encoded miR-BART5-5p upregulates PD-L1 through PIAS3/pSTAT3 modulation, worsening clinical outcomes of PD-L1-positive gastric carcinomas

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page