title: Expressions of the CagA protein and CagA-signaling molecules predict Helicobacter pylori dependence of early-stage gastric DLBCL.
abstract: We previously reported that early-stage gastric diffuse large B-cell lymphomas (DLBCLs), including DLBCLs with mucosa-associated lymphoid tissue (DLBCL[MALT]) and without ("pure" DLBCL) the features of MALT lymphomas, can achieve long-term complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We recently reported that expression of cytotoxin-associated gene A (CagA) and CagA-signaling molecules (phospho-Src homology-2 domain-containing phosphatase [p-SHP2] and phospho-extracellular signal-regulated kinase [p-ERK]) is associated with HP dependence of gastric MALT lymphoma. However, the significance of CagA and CagA-signaling molecules in gastric DLBCL remains unexplored. The association between expression of CagA, p-SHP-2, and p-ERK in malignant B cells and tumor response to HPE was evaluated in 63 patients with stage IE/IIE1 HP-positive gastric DLBCL who received HPE as frontline treatment. We detected CagA expression in 20 of 42 DLBCL (MALT) cases (47.6%) and in 13 of 21 "pure" DLBCL cases (61.9%). CagA expression was higher in HP-dependent tumors than in HP-independent tumors (74.3% [26 of 35] vs 25.0% [7 of 28]). Patients with CagA expression responded to HPE quicker than those without expression (median time to complete remission, 4.0 months vs 5.0 months). The expression of CagA was closely associated with p-SHP-2 and p-ERK expression. Combined CagA, p-SHP-2, and p-ERK expression showed an increased positive predictive value (81.8% vs 75.9%) and an increased specificity (84.0% vs 75.0%) for HP dependence compared with CagA expression alone. Our results indicated that CagA and its signaling molecules can be detected in the malignant B cells of gastric DLBCL, and the expression of these molecules is clinically and biologically associated with HP dependence.
authors.affiliation: Department of Oncology and.|Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|National Taiwan University Cancer Center and.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Sung-Hsin
authors.identifier: 0000-0003-0054-887X
authors.initials: SH
authors.lastname: Kuo
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.|Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan; and.
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chung-Wu
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Oncology and.|National Taiwan University Cancer Center and.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kun-Huei
authors.initials: KH
authors.lastname: Yeh
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.affiliation: Department of Oncology and.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Shin
authors.initials: YS
authors.lastname: Tzeng
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Liou
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ping-Ning
authors.initials: PN
authors.lastname: Hsu
authors.affiliation: Department of Oncology and.|Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|National Taiwan University Cancer Center and.|Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.|National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000942:Antigens, Bacterial / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005260:Female; D016481:Helicobacter Infections / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000382:microbiology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D048049:Extracellular Signal-Regulated MAP Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11