Refractory remodeling of the microenvironment by abnormal type V collagen, apoptosis, and immune response in non-small cell lung cancer.

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.