title: Protocadherin γ A3 is expressed in follicular lymphoma irrespective of BCL2 status and is associated with tumor cell growth.
abstract: Protocadherin genes (PCDHs) have been suggested to act as tumor suppressor genes in various tumor types. Previous studies have demonstrated the upregulation of certain PCDH‑γ subfamily genes in nodal and duodenal follicular lymphoma (FL) using gene expression analyses. However, the mechanisms and associated molecular function of PCDH‑γ subfamily gene upregulation in FL remain to be elucidated. The present study examined the expression of PCDHGA3, an upregulated PCDH‑γ gene subfamily member, in B‑cell lymphoma 2 (BCL2)‑positive and ‑negative FL, and evaluated its association with tumor cell proliferation in an FL‑derived cell line. Immunohistochemical analysis demonstrated that the majority of FL grade 1‑2 samples (19/20; 95%) and over half of grade 3A FL samples (5/9; 56%) were PCDHGA3‑positive, whereas only 1/17 reactive lymphoid hyperplasia samples was positive. Notably, this positivity was widely observed in samples of BCL2‑negative FL (13/15; 87%) and FL with diffuse area (10/10; 100%). The FL‑derived cell line FL18 exhibited strong PCDHGA3 expression, similar to the patient samples, and its proliferation was suppressed by PCDHGA3 gene knockdown. Genes expressed concomitantly with PCDHGA3 were selected from gene expression data, and TNFRSF6B, a member of the tumor necrosis factor receptor superfamily, was among the top five most strongly correlated genes. Coexpression of TNFRSF6B and PCDHGA3 was observed immunohistochemically in FL18 cells, suggesting potential cooperation in tumor cell maintenance. In conclusion, the results of the present study indicated that PCDHGA3 was expressed in FL irrespective of BCL2 status and grading and was associated with cell proliferation. Further studies involving molecular genetic analyses are required to elucidate the mechanisms underlying the activity of PCDHGA3 in FL.
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyata-Takata
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Noujima-Harada
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins; D019253:Proto-Oncogene Proteins c-bcl-2; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C505911:TNFRSF6B protein, human