title: Refractory remodeling of the microenvironment by abnormal type V collagen, apoptosis, and immune response in non-small cell lung cancer.
abstract: Collagen V shows promise as an inducer of the death response via caspases. Remodeling of the microenvironment by collagen V, tumoral/vascular apoptosis, and the immune response were evaluated, based on the prognosis of 65 patients with surgically excised non-small cell lung cancer. Immunofluorescence, immunohistochemistry, morphometry, tridimensional reconstruction, and a real-time polymerase chain reaction were used to evaluate the amount, structure, and molecular chains of collagen V, tumoral and vascular apoptosis, immune cells, and microvessel density. The impact of these markers was tested on follow-up until death from recurrent lung cancer occurred. A decreased and abnormal synthesis of collagen V was found to lead to increased angiogenesis due to a low endothelial death rate and a low immune response. A Cox model analysis, controlled for the lymph node stage, demonstrated that only collagen V and vascular apoptosis variables were significantly associated with survival time. A point at the median for collagen V and vascular apoptosis divided patients into 2 groups, each with a distinctive prognosis. Those with a collagen V higher than 9.40% and vascular apoptosis higher than 1.09% had a low risk of death (0.27 and 0.41, respectively) compared to those with a collagen V lower than 9.40% and vascular apoptosis lower than 1.09%. Collagen V and vascular apoptosis in resected non-small cell lung cancer was strongly related to the prognosis, suggesting that strategies aimed at preventing low collagen V synthesis, or local responses to low vascular apoptosis may have a greater impact in lung cancer treatment.
authors.affiliation: Departament of Pathology, Faculdade de Medicina da Universidade de São Paulo 01246-903, Brazil.
authors.forename: Paola
authors.initials: P
authors.lastname: Souza
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Rizzardi
authors.forename: Gustavo
authors.initials: G
authors.lastname: Noleto
authors.forename: Marcelo
authors.initials: M
authors.lastname: Atanazio
authors.forename: Osmar
authors.initials: O
authors.lastname: Bianchi
authors.forename: Edwin Roger
authors.initials: ER
authors.lastname: Parra
authors.forename: Walcy Rosolia
authors.initials: WR
authors.lastname: Teodoro
authors.forename: Solange
authors.initials: S
authors.lastname: Carrasco
authors.forename: Ana Paula Pereira
authors.initials: AP
authors.lastname: Velosa
authors.forename: Sandra
authors.initials: S
authors.lastname: Fernezlian
authors.forename: Alexandre Muxfeldt
authors.initials: AM
authors.lastname: Ab'saber
authors.forename: Leila
authors.initials: L
authors.lastname: Antonângelo
authors.forename: Tereza
authors.initials: T
authors.lastname: Takagaki
authors.forename: Cláudia Goldenstein
authors.initials: CG
authors.lastname: Schainberg
authors.forename: Natalino Hajime
authors.initials: NH
authors.lastname: Yoshinari
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D024062:Collagen Type V / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D024042:Collagen Type I; D024061:Collagen Type III; D024062:Collagen Type V; D012333:RNA, Messenger; D053453:Caspase 9