title: CD45RO(+) Memory T Lymphocytes--a Candidate Marker for TNM-Immunoscore in Squamous Non-Small Cell Lung Cancer.
abstract: Tumor-infiltrating lymphocytes (TILs) are vital in limiting cancer progression and may supplement the TNM classification. CD45RO(+) memory TILs show major prognostic impact in various malignancies but have not been extensively explored in non-small cell lung cancer (NSCLC). In this study, we aimed to evaluate their potential in a NSCLC TNM-Immunoscore. Tissue microarrays were constructed from tumor tissue samples from two cohorts including in total 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC. The density of CD45RO(+) and CD8(+) TILs in tumor epithelial and stromal compartments of the tumors was evaluated by immunohistochemistry. In univariate analyses, intraepithelial CD45RO(+) TIL density (T-CD45RO) was a significant prognostic factor for disease-specific survival (P = .007), limited to the squamous cell carcinoma (SCC) histology subgroup (P < .001), where it was significant in both cohorts (University Hospital of North Norway, P = .003; Nordland Hospital, P = .022). Combining T-CD45RO and stromal CD8(+) TIL density (S-CD8) increased the prognostic impact in SCC (P < .001) and showed a significant impact within all pathological stages (I, P = .025; II, P < .001; III, P = .001). In the multivariate analysis, T-CD45RO was an independent positive prognostic factor for SCC (hazard ratio 2.65, 95% confidence interval 1.64-4.28, P < .001), and in combination with S-CD8, the prognostic impact increased vastly (high + high versus low + low: hazard ratio 6.50, 95% confidence interval 3.54-11.91, P < .001). In conclusion, T-CD45RO was an independent prognostic factor for SCC NSCLC. When combined with S-CD8, the prognostic impact increased and was significant within each pathological stage. We propose CD45RO as a candidate marker for TNM-Immunoscore in SCC NSCLC.
authors.affiliation: Department of Oncology, University Hospital of North Norway, Mailbox 100, N-9038 Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Mailbox 6050 Langnes, N-9037 Tromso, Norway. Electronic address: epa014@post.uit.no.
authors.forename: Erna-Elise
authors.initials: EE
authors.lastname: Paulsen
authors.affiliation: Department of Oncology, University Hospital of North Norway, Mailbox 100, N-9038 Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Mailbox 6050 Langnes, N-9037 Tromso, Norway. Electronic address: kilvaer@gmail.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kilvaer
authors.affiliation: Department of Medical Biology, UiT The Arctic University of Norway, Mailbox 6050 Langnes, N-9037 Tromso, Norway. Electronic address: mkh011@post.uit.no.
authors.forename: Mehrdad Rakaee
authors.initials: MR
authors.lastname: Khanehkenari
authors.affiliation: Department of Pathology, Nordland Hospital, Mailbox 1480, 8092 Bodoe, Norway. Electronic address: ramonajohansen1@hotmail.com.
authors.forename: Ramona Johansen
authors.initials: RJ
authors.lastname: Maurseth
authors.affiliation: Department of Clinical Pathology, University Hospital of North Norway, Mailbox 100, N-9038 Tromso, Norway. Electronic address: samer.al-saad@unn.no.
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.affiliation: Department of Clinical Medicine, UiT The Arctic University of Norway, Mailbox 6050 Langnes, N-9037 Tromso, Norway. Electronic address: sigurd.hald@uit.no.
authors.forename: Sigurd M
authors.initials: SM
authors.lastname: Hald
authors.affiliation: Department of Pathology, Nordland Hospital, Mailbox 1480, 8092 Bodoe, Norway. Electronic address: khalidshibli@gmail.com.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.affiliation: Department of Oncology, University Hospital of North Norway, Mailbox 100, N-9038 Tromso, Norway. Electronic address: sigve.andersen@uit.no.
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.affiliation: Department of Clinical Pathology, University Hospital of North Norway, Mailbox 100, N-9038 Tromso, Norway; Department of Medical Biology, UiT The Arctic University of Norway, Mailbox 6050 Langnes, N-9037 Tromso, Norway. Electronic address: elin.richardsen@unn.no.
authors.forename: Elin
authors.initials: E
authors.lastname: Richardsen
authors.affiliation: Department of Clinical Pathology, University Hospital of North Norway, Mailbox 100, N-9038 Tromso, Norway; Department of Medical Biology, UiT The Arctic University of Norway, Mailbox 6050 Langnes, N-9037 Tromso, Norway. Electronic address: lill-tove.busund@unn.no.
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.affiliation: Department of Oncology, University Hospital of North Norway, Mailbox 100, N-9038 Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Mailbox 6050 Langnes, N-9037 Tromso, Norway. Electronic address: roy.bremnes@uit.no.
authors.forename: Roy
authors.initials: R
authors.lastname: Bremnes
authors.affiliation: Department of Oncology, University Hospital of North Norway, Mailbox 100, N-9038 Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Mailbox 6050 Langnes, N-9037 Tromso, Norway. Electronic address: tom.donnem@uit.no.
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D017493:Leukocyte Common Antigens