{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:33:12Z","timestamp":1779910392917,"version":"3.53.1"},"reference-count":36,"publisher":"Societatea Romana de Morfologie","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rom J Morphol Embryol"],"published-print":{"date-parts":[[2025,12,12]]},"abstract":"<jats:p>Tumor heterogeneity and the multitude of mechanisms involved in the progression of gastric adenocarcinomas (GACs) are reflected in the incidence and mortality rates, which continue to be a problem in oncological pathology. The way in which immune inflammatory elements intervene in the modeling of the tumor environment and influence gastric carcinogenesis is insufficiently known. The study investigated the intratumoral and peritumoral distribution and density of T- and B-lymphocytes and macrophages in 54 cases of GAC in relation to the histological prognostic parameters of the tumors. Discohesive, mixed and tubular adenocarcinomas presented the highest value of cluster of differentiation (CD)45RO reactions in the tumor compartments. In the case of GAC with associated histological aggressiveness parameters, we found higher values of CD20 and CD68 reactions at the intratumoral level, and of CD45RO peritumorally, which suggests different immune immunophenotypes not only in relation to the tumor type, grade and stage, but also to the two compartments. These observations may be useful for establishing criteria for approaching and interfering with immune mechanisms in gastric carcinogenesis, which may improve patient prognosis.<\/jats:p>","DOI":"10.47162\/rjme.66.3.07","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:41:45Z","timestamp":1768819305000},"page":"501-509","source":"Crossref","is-referenced-by-count":1,"title":["Immunohistochemical quantification of inflammation associated with gastric adenocarcinomas"],"prefix":"10.47162","volume":"66","author":[{"name":"PhD Student, Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana-Andreea","family":"Pisic\u0103-Ilinca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana-Iulia","family":"Cre\u0163u","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca C\u0103t\u0103lina","family":"Andreiana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Badiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudiu","family":"M\u0103rg\u0103ritescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca-Niculina","family":"Ciurea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela Marinela","family":"Florescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda Elena","family":"Cri\u015fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Medical Oncology, University of Medicine and Pharmacy of Craiova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u0103zvan Grigora\u015f","family":"C\u0103pit\u0103nescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex Emilian","family":"Stepan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Department of Pathology, University of Medicine and Pharmacy of Craiova, Romania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"26736","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"\"[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3):209-249. https:\/\/doi.org\/10.3322\/caac.21660","DOI":"10.3322\/caac.21660"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"[2] Park JY, Georges D, Alberts CJ, Bray F, Clifford G, Baussano I. Global lifetime estimates of expected and preventable gastric cancers across 185 countries. Nat Med, 2025, 31(9):3020-3027. https:\/\/doi.org\/10.1038\/s41591-025-03793-6","DOI":"10.1038\/s41591-025-03793-6"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"[3] Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol, 2019, 14(1):26-38. https:\/\/doi.org\/10.5114\/pg.2018.80001","DOI":"10.5114\/pg.2018.80001"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"[4] Luo D, Liu Y, Lu Z, Huang L. Targeted therapy and immunotherapy for gastric cancer: rational strategies, novel advancements, challenges, and future perspectives. Mol Med, 2025, 31(1):52. https:\/\/doi.org\/10.1186\/s10020-025-01075-y","DOI":"10.1186\/s10020-025-01075-y"},{"key":"ref4","unstructured":"[5] Florescu DE, Stepan AE, M\u0103rg\u0103ritescu C, Ciurea RN, Stepan MD, Simionescu CE. The involvement of EGFR, HER2 and HER3 in the basal cell carcinomas aggressiveness. Rom J Morphol Embryol, 2018, 59(2):479-484. PMID: 30173251"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"[6] Wakatsuki K, Sho M, Yamato I, Takayama T, Matsumoto S, Tanaka T, Migita K, Ito M, Hotta K, Nakajima Y. Clinical impact of tumor-infiltrating CD45RO+ memory T cells on human gastric cancer. Oncol Rep, 2013, 29(5):1756-1762. https:\/\/doi.org\/10.3892\/or.2013.2302","DOI":"10.3892\/or.2013.2302"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"[7] Lee HE, Chae SW, Lee YJ, Kim MA, Lee HS, Lee BL, Kim WH. Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer. Br J Cancer, 2008, 99(10):1704-1711. https:\/\/doi.org\/10.1038\/sj.bjc.6604738","DOI":"10.1038\/sj.bjc.6604738"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"[8] Marrogi AJ, Munshi A, Merogi AJ, Ohadike Y, El-Habashi A, Marrogi OL, Freeman SM. Study of tumor infiltrating lymphocytes and transforming growth factor-beta as prognostic factors in breast carcinoma. Int J Cancer, 1997, 74(5):492-501. https:\/\/doi:10.1002\/(sici)1097-0215(19971021)74:5<492::aid-ijc3>3.0.co;2-z","DOI":"10.1002\/(SICI)1097-0215(19971021)74:5<492::AID-IJC3>3.0.CO;2-Z"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"[9] Zhang J, Hu Z, Horta CA, Yang J. Regulation of epithelial-mesenchymal transition by tumor microenvironmental signals and its implication in cancer therapeutics. Semin Cancer Biol, 2023, 88:46-66. https:\/\/doi.org\/10.1016\/j.semcancer.2022.12.002","DOI":"10.1016\/j.semcancer.2022.12.002"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"[10] Whiteside TL. Tumor-infiltrating lymphocytes and their role in solid tumor progression. Exp Suppl, 2022, 113:89-106. https:\/\/doi.org\/10.1007\/978-3-030-91311-3_3","DOI":"10.1007\/978-3-030-91311-3_3"},{"key":"ref10","unstructured":"[11] Stepan AE, Ciurea RN, Dr\u0103goescu PO, Florescu MM, Stepan MD. Immunoexpression of transcription factors in urothelial bladder carcinomas. Rom J Morphol Embryol, 2017, 58(3):863-869."},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"[12] Niculescu \u015eA, Grecu DC, Simionescu CE, Niculescu EC, Stepan MD, Stepan AE. Immunoexpression of Ki67, p53 and cyclin D1 in osteosarcomas. Rom J Morphol Embryol, 2021, 62(3):743-750. https:\/\/doi.org\/10.47162\/RJME.62.3.11","DOI":"10.47162\/RJME.62.3.11"},{"key":"ref12","unstructured":"[13] World Health Organization (WHO) Classification of Tumours Editorial Board. Digestive system tumours. 5th edition, vol. 1, WHO Classification of Tumours, International Academy of Pathology, International Agency for Research on Cancer (IARC) Press, Lyon, France, 2019."},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"[14] Seidl M, Bader M, Vaihinger A, Wellner UF, Todorova R, Herde B, Schrenk K, Maurer J, Schilling O, Erbes T, Fisch P, Pfeiffer J, Hoffmann L, Franke K, Werner M, Bronsert P. Morphology of immunomodulation in breast cancer tumor draining lymph nodes depends on stage and intrinsic subtype. Sci Rep, 2018, 8(1):5321. https:\/\/doi.org\/10.1038\/s41598-018-23629-3","DOI":"10.1038\/s41598-018-23629-3"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"[15] Ieni A, Barresi V, Rigoli L, Fedele F, Tuccari G, Caruso RA. Morphological and cellular features of innate immune reaction in Helicobacter pylori gastritis: a brief review. Int J Mol Sci, 2016, 17(1):109. https:\/\/doi.org\/10.3390\/ijms17010109","DOI":"10.3390\/ijms17010109"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"[16] Dumitru I, Zoril\u0103 MV, \u0162olescu R\u015e, Racil\u0103 L, Pascu CI, Oprica AC, Burghil\u0103 DV, Matei L, V\u00eelcea EJ, Popescu C, Badea-Voiculescu O, Mogoant\u0103 L. Experimental model for the study of traumatic brain injury. Rom J Morphol Embryol, 2020, 61(3):729-737. https:\/\/doi.org\/10.47162\/RJME.61.3.11","DOI":"10.47162\/RJME.61.3.11"},{"key":"ref16","unstructured":"[17] Florou C, Zoril\u0103 AL, Zoril\u0103 MV, Marinescu MA, Andrei CM, P\u0103v\u0103loiu RM, Mogoant\u0103 L, Z\u0103voi RE. Clinico-statistical and morphological aspects of severe traumatic brain injuries. Rom J Morphol Embryol, 2016, 57(2):391-400."},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"[18] Kang BW, Seo AN, Yoon S, Bae HI, Jeon SW, Kwon OK, Chung HY, Yu W, Kang H, Kim JG. Prognostic value of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric cancer. Ann Oncol, 2016, 27(3):494-501. https:\/\/doi.org\/10.1093\/annonc\/mdv610","DOI":"10.1093\/annonc\/mdv610"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"[19] Tone T, Tauv\u0113na E, Strumfa I, Gardovskis J. Inflammatory cells in gastric cancer: promoting the tumour or protecting the host? Proc Latv Acad Sci Sect B Nat Exact Appl Sci, 2020, 74(2):111-117. https:\/\/doi.org\/10.2478\/prolas-2020-0018","DOI":"10.2478\/prolas-2020-0018"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"[20] Devi M, Vijayalakshmi D, Dhivya K, Janane M. Memory T cells (CD45RO) role and evaluation in pathogenesis of lichen planus and lichenoid mucositis. J Clin Diagn Res, 2017, 11(5):ZC84-ZC86. https:\/\/doi.org\/10.7860\/JCDR\/2017\/26866.9930","DOI":"10.7860\/JCDR\/2017\/26866.9930"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"[21] Hu G, Wang S. Tumor-infiltrating CD45RO+ memory T lymphocytes predict favorable clinical outcome in solid tumors. Sci Rep, 2017, 7(1):10376. https:\/\/doi.org\/10.1038\/s41598-017-11122-2","DOI":"10.1038\/s41598-017-11122-2"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"[22] Soeratram TTD, Biesma HD, Egthuijsen JMP, Meershoek-Klein Kranenbarg E, Hartgrink HH, van de Velde CJH, Mookhoek A, van Dijk E, Kim Y, Ylstra B, van Laarhoven HWM, van Grieken NCT. Prognostic value of T-cell density in the tumor center and outer margins in gastric cancer. Mod Pathol, 2023, 36(9):100218. https:\/\/doi.org\/10.1016\/j.modpat.2023.100218","DOI":"10.1016\/j.modpat.2023.100218"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"[23] P\u0103tra\u015fcu \u015e, Cercelaru L, Graure GM, Firu\u0163 MA, Rotaru I, C\u00e2r\u0163u D, Marinescu D, P\u0103tra\u015fcu AM, Radu RI, Mitroi G, \u015eurlin V. The histopathological features and their prognostic impact in the postoperative follow-up of colorectal cancer patients. Rom J Morphol Embryol, 2022, 63(3):555-561. https:\/\/doi.org\/10.47162\/RJME.63.3.10","DOI":"10.47162\/RJME.63.3.10"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"[24] Szor DJ, Dias AR, Pereira MA, Ramos MFKP, Zilberstein B, Cecconello I, Ribeiro-J\u00fanior U. Prognostic role of neutrophil\/lymphocyte ratio in resected gastric cancer: a systematic review and meta-analysis. Clinics (Sao Paulo), 2018, 73:e360. https:\/\/doi.org\/10.6061\/clinics\/2018\/e360","DOI":"10.6061\/clinics\/2018\/e360"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"[25] Coussens LM, Werb Z. Inflammation and cancer. Nature, 2002, 420(6917):860-867. https:\/\/doi.org\/10.1038\/nature01322","DOI":"10.1038\/nature01322"},{"key":"ref25","unstructured":"[26] Bosman FT, Carneiro F, Hruban RH, Theise ND (eds). World Health Organization (WHO) Classification of tumours of the digestive system. WHO Classification of Tumours, 4th edition, vol. 3. International Agency for Research on Cancer (IARC) Press, Lyon, France, 2010."},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"[27] Lee JS, Won HS, Sun DS, Hong JH, Ko YH. Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a systematic review and meta-analysis. Medicine (Baltimore), 2018, 97(32):e11769. https:\/\/doi.org\/10.1097\/MD.0000000000011769","DOI":"10.1097\/MD.0000000000011769"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"[28] Thaunat O, Morelon E, Defrance T. Am\"B\"valent: anti-CD20 antibodies unravel the dual role of B cells in immunopathogenesis. Blood, 2010, 116(4):515-521. https:\/\/doi.org\/10.1182\/blood-2010-01-266668","DOI":"10.1182\/blood-2010-01-266668"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"[29] Tomchuk O. A105: Morphological characteristics and clinical significance of tumor infiltrating CD20 B lymphocytes in gastric cancer. Eur J Cancer Suppl, 2015, 13(1):62-63. https:\/\/doi.org\/10.1016\/j.ejcsup.2015.08.111","DOI":"10.1016\/j.ejcsup.2015.08.111"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"[30] Dong J, Li J, Liu SM, Feng XY, Chen S, Chen YB, Zhang XS. CD33+\/p-STAT1+ double-positive cell as a prognostic factor for stage IIIa gastric cancer. Med Oncol, 2013, 30(1):442. https:\/\/doi.org\/10.1007\/s12032-012-0442-2","DOI":"10.1007\/s12032-012-0442-2"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"[31] Fristedt R, Borg D, Hedner C, Berntsson J, Nodin B, Eberhard J, Micke P, Jirstr\u00f6m K. Prognostic impact of tumour-associated B cells and plasma cells in oesophageal and gastric adenocarcinoma. J Gastrointest Oncol, 2016, 7(6):848-859. https:\/\/doi.org\/10.21037\/jgo.2016.11.07","DOI":"10.21037\/jgo.2016.11.07"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"[32] Gambardella V, Castillo J, Tarazona N, Gimeno-Valiente F, Mart\u00ednez-Ciarpaglini C, Cabeza-Segura M, Rosell\u00f3 S, Roda D, Huerta M, Cervantes A, Fleitas T. The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target. Cancer Treat Rev, 2020, 86:102015. https:\/\/doi.org\/10.1016\/j.ctrv.2020.102015","DOI":"10.1016\/j.ctrv.2020.102015"},{"key":"ref32","unstructured":"[33] Dobri\u0163oiu M, Stepan AE, M\u0103rg\u0103ritescu C, Simionescu CE, Vere CC, Schenker M, Cri\u015fan AE. Immunoexpression of E-cadherin, P-cadherin and fibronectin in gastric carcinomas. Rom J Morphol Embryol, 2019, 60(2):573-579."},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"[34] Jeremiasen M, Borg D, Hedner C, Svensson M, Nodin B, Leandersson K, Johansson J, Jirstr\u00f6m K. Tumor-associated CD68+, CD163+, and MARCO+ macrophages as prognostic biomarkers in patients with treatment-na\u00efve gastroesophageal adenocarcinoma. Front Oncol, 2020, 10:534761. https:\/\/doi.org\/10.3389\/fonc.2020.534761","DOI":"10.3389\/fonc.2020.534761"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"[35] Zhang J, Yan Y, Yang Y, Wang L, Li M, Wang J, Liu X, Duan X, Wang J. High infiltration of tumor-associated macrophages influences poor prognosis in human gastric cancer patients, associates with the phenomenon of EMT. Medicine (Baltimore), 2016, 95(6):e2636. https:\/\/doi.org\/10.1097\/MD.0000000000002636","DOI":"10.1097\/MD.0000000000002636"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"[36] Wu H, Xu JB, He YL, Peng JJ, Zhang XH, Chen CQ, Li W, Cai SR. Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer. J Surg Oncol, 2012, 106(4):462-468. https:\/\/doi.org\/10.1002\/jso.23110\"","DOI":"10.1002\/jso.23110"}],"container-title":["Romanian Journal of Morphology and Embryology"],"original-title":[],"link":[{"URL":"https:\/\/rjme.ro\/RJME\/resources\/files\/660325501509.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:46:38Z","timestamp":1768819598000},"score":1,"resource":{"primary":{"URL":"https:\/\/rjme.ro\/archive\/66\/3\/7\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,8]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,12,12]]},"published-print":{"date-parts":[[2025,12,12]]}},"URL":"https:\/\/doi.org\/10.47162\/rjme.66.3.07","relation":{},"ISSN":["1220-0522","2066-8279"],"issn-type":[{"value":"1220-0522","type":"print"},{"value":"2066-8279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,8]]}}}