title: Recurrence of squamous cell lung carcinoma is associated with the co-presence of reactive lesions in tumor-adjacent bronchial epithelium.
abstract: Recurrences occur in 30 % of lung cancer patients after radical therapy; however, known prognostic factors are not always effective. In this study, we investigated whether the frequency of squamous non-small cell lung cancer (NSCLC) recurrence depends on the presence of reactive lesions in tumor-adjacent bronchial epithelium. Specimens of adjacent lung tissue from 104 patients with squamous NSCLC were used for the determination of basal cell hyperplasia (BCH) and squamous metaplasia (SM) and for the analysis of the expression of Ki-67, p53, Bcl-2, and CD138. We found that recurrence was observed in 36.7 % of patients with BCH combined with SM (BCH + SM+) in the same bronchus, compared with 1.8 % in patients with isolated BCH (BCH + SM-; odds ratio (OR) 31.26, 95 % confidence interval (CI) 3.77-258.60; p = 0.00002). The percentage of Ki-67-positive cells was significantly higher in BCH + SM+ than in BCH + SM- (34.9 vs. 18.3 %; effect size 2.86, 95 % CI 2.23-3.47; p = 0.003). P53 expression was also more significant in BCH + SM+ than in BCH + SM- (14.4 vs. 9.6 %; effect size 1.22, 95 % CI 0.69-1.76; p = 0.0008). In contrast, CD138 expression was lower in BCH + SM+ than in BCH + SM- (21.8 vs. 38.5 %; effect size -6.26, 95 % CI -7.31 to -5.22; p = 0.003). Based on our results, we concluded that the co-presence of reactive bronchial lesions is associated with the development of recurrent squamous NSCLC and may be a negative prognostic indicator. In addition, significant differences in Ki-67, p53, and CD138 expression exist between isolated BCH and BCH combined with SM that probably reflect part of biological differences, which could relate to the mechanism of lung cancer recurrence.
authors.affiliation: Department of Pathological Anatomy and Cytology, Tomsk Cancer Research Institute, Kooperativny Str. 5, Tomsk, Russian Federation, 634050.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Pankova
authors.affiliation: Laboratory of Molecular Oncology and Immunology, Tomsk Cancer Research Institute, Kooperativny Str. 5, Tomsk, Russian Federation, 634050. d_evgeniy@oncology.tomsk.ru.|Laboratory for Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, 36, Lenina Avenue, Tomsk, Russian Federation, 634050. d_evgeniy@oncology.tomsk.ru.|Department of Organic Chemistry, National Research Tomsk State University, 36, Lenina Avenue, Tomsk, Russian Federation, 634050. d_evgeniy@oncology.tomsk.ru.
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Denisov
authors.affiliation: Laboratory of Molecular Oncology and Immunology, Tomsk Cancer Research Institute, Kooperativny Str. 5, Tomsk, Russian Federation, 634050.|National Research Tomsk Polytechnic University, 30, Lenina Avenue, Tomsk, Russian Federation, 634050.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Ponomaryova
authors.affiliation: Laboratory of Molecular Oncology and Immunology, Tomsk Cancer Research Institute, Kooperativny Str. 5, Tomsk, Russian Federation, 634050.|Laboratory for Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, 36, Lenina Avenue, Tomsk, Russian Federation, 634050.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Gerashchenko
authors.affiliation: Department of Thoracoabdominal Oncology, Tomsk Cancer Research Institute, Kooperativny Str. 5, Tomsk, Russian Federation, 634050.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Tuzikov
authors.affiliation: Department of Pathological Anatomy and Cytology, Tomsk Cancer Research Institute, Kooperativny Str. 5, Tomsk, Russian Federation, 634050.|Department of Pathological Anatomy, Siberian State Medical University, Moscowski Trakt, 2, Tomsk, Russian Federation, 634050.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Perelmuter
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008679:Metaplasia; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D053668:Syndecan-1 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D053668:Syndecan-1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Hyperplasia; Immunohistochemistry; Lung cancer; Metaplasia; Recurrence