Current Concepts in Bronchioloalveolar Carcinoma Biology

Raz, Dan J.; He, Biao; Rosell, Rafael; Jablons, David M.

doi:10.1158/1078-0432.ccr-06-0457

Cited by 43 publications

(28 citation statements)

References 62 publications

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“…Although traditionally grouped with other non -small cell lung cancers, BAC has unique morphologic features and clinical behavior related to its aerogenous spreading. At an early stage of diagnosis, focal BAC is usually cured by surgical resection, whereas at a later stage (1,2), the multifocal or diffuse form is characterized by pulmonary progression and death due to respiratory insufficiency rather than to dissemination (3). For these patients, optimal therapy still needs to be defined, although several recent studies report that some patients are showing significant responses to tyrosine kinase inhibitors of epidermal growth factor receptor (4).…”

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confidence: 99%

Neutrophils Promote Aerogenous Spread of Lung Adenocarcinoma with Bronchioloalveolar Carcinoma Features

Wislez

Antoine

Rabbe

et al. 2007

Clinical Cancer Research

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Purpose: Adenocarcinoma with bronchioloalveolar carcinoma (BAC) features is a subtype of non^small cell lung cancers characterized by an intense inflammatory reaction composed of macrophages and neutrophils and by a distinct natural history with intrapulmonary spread leading to death due to respiratory failure. We hypothesized that neutrophils could promote aerogenous spread of lung adenocarcinoma with BAC features. Experimental Design: We examined the effect of neutrophils on A549 cell line detachment in vitro and we quantified desquamation of tumor cells on tumor tissue (n = 25) and on matched bronchioloalveolar lavage (n = 17) in vivo in a series of patients with adenocarcinoma with BAC features. Results: Neutrophils induced A549 detachment mediated by signals through cell-to-cell contact. Detached A549 cells were still viable and able to proliferate in vitro. Neutralization studies identified several membrane-bound molecules involved in detachment (i.e., intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, tumor necrosis factor a/tumor necrosis factor a receptor inhibitor, interleukin-1a /interleukin-1a receptor, and neutrophil elastase). In tumor tissue, shedding was detected in all samples, with a median shedding score of 42% (range, 4-95%). Micropapillary clusters were detected in 23 of the 25 tumor tissue samples, with a median micropapillary score of 1.40 (range, 0-2.1), and tumor cells were detected in 7 of 17 lavages. The micropapillary score was associated with a high neutrophil count in bronchioloalveolar lavage (P = 0.051). The shedding cell percentage was a significant factor in shorter survival (P = 0.034, univariate Cox analysis). Conclusions: Tumor shedding is induced by neutrophils. It is a significant factor of shorter survival and may be an important event in adenocarcinoma progression.

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confidence: 99%

Neutrophils Promote Aerogenous Spread of Lung Adenocarcinoma with Bronchioloalveolar Carcinoma Features

Wislez

Antoine

Rabbe

et al. 2007

Clinical Cancer Research

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“…In mixed adenocarcinomas, with a variable amount of BAC component, CLU expression was intermediate, being present in 69% of cases; furthermore, CLU expression was directly related to the amount of BAC component, decreasing with the increased invasiveness of the lesions. The molecular events that regulate the multistep carcinogenesis -hypothesized in lung adenocarcinoma -are currently unknown, but multiple pathways and genetic changes are certainly implicated [27][28][29][30][31]. The progressive decrease of CLU expression is clearly one of the molecular changes implicated in the progression from pure BAC to invasive adenocarcinoma, and confirm the possible role of CLU as a tumor suppressor factor against infiltration or invasiveness.…”

Section: Discussionmentioning

confidence: 88%

Prognostic role of clusterin in resected adenocarcinomas of the lung

et al. 2013

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a b s t r a c tRationale: Clusterin expression may change in various human malignancies, including lung cancer. Patients with resectable non-small cell lung cancer (NSCLC), including adenocarcinoma, have a poor prognosis, with a relapse rate of 30-50% within 5 years. Nuclear factor kB (Nf-kB) is an intracellular protein involved in the initiation and progression of several human cancers, including the lung. Objectives: We investigate the role of clusterin and Nf-kB expression in predicting the prognosis of patients with early-stage surgically resected adenocarcinoma of the lung. Findings: The level of clusterin gradually decreased from well-differentiated to poorly differentiated adenocarcinomas. Clusterin expression was significantly higher in patients with low-grade adenocarcinoma, in early-stage disease and in women. Clusterin expression was inversely related to relapse and survival in both univariate and multivariate analyses. Finally, we observed an inverse correlation between Nf-kB and clusterin. Conclusions: Clusterin expression represents an independent prognostic factor in surgically resected lung adenocarcinoma and was proven to be a useful biomarker for fewer relapses and longer survival in patients in the early stage of disease. The inverse correlation between Nf-kB and clusterin expression confirm the previously reported role of clusterin as potent down regulator of Nf-kB.

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“…12 ). Alternatively, the degree of neutrophil infiltration in BAC is associated with poor prognosis 13 . Although not the initiator of either IPF or BAC pathogenesis, the number of neutrophilic elements in the lesion and increased oxidative stress may indicate a possible link between IPF and BAC.…”

Section: Discussionmentioning

confidence: 99%