ABSTRACT
CONTEXT: Angiogenesis is essential for tumors to grow and metastasize. Lymphatic metastasis is also an important means of tumor spread. In non-small cell lung carcinoma, the relationship of lymphangiogenesis with lymph node metastasis and, ultimately, patient prognosis is unknown. OBJECTIVE: To evaluate whether lymphangiogenesis is related to lymph node metastasis and/or overall survival. DESIGN: Seventy-eight cases of non-small cell lung carcinoma diagnosed from 1987 to 2004 were retrospectively analyzed for intratumoral, peritumoral, and uninvolved adjacent lung tissue lymphatic vessel density (LVD) by D2-40 immunostaining. Lymphatics in 6 cases of squamous dysplasia/carcinoma in situ were similarly evaluated. Appropriate statistical methods were used. RESULTS: Intratumoral and peritumoral LVD was significantly higher than in the uninvolved adjacent lung but showed no significant association with lymph node stage at the time of tumor resection. Survival in patients with above average D2-40 values was not significantly different when compared with those who had below average values (median survival, 895 vs 1131 days; P = .97). Furthermore, patients with affected lymph nodes had significantly shorter survival (median survival, 467 vs 1425 days; P = .002). Overall, regardless of lymph node status, there was a significantly higher intratumoral (P < .001) and peritumoral (P < .001) LVD when compared with the adjacent uninvolved lung LVD. There was a trend toward increasing LVD with higher grade of squamous dysplasia. CONCLUSIONS: The results suggest that although lymphangiogenesis occurs in association with non-small cell lung carcinoma, it may not be an important factor in lymph node metastasis. In fact, there is a suggestion that the number of lymphatics that a person inherently has appears to be more important than lymphangiogenesis when it comes to the development of lymph node metastasis.
Subject(s)
Carcinoma, Non-Small-Cell Lung/physiopathology , Lung Neoplasms/physiopathology , Lymphangiogenesis/physiology , Lymphatic Metastasis/physiopathology , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal, Murine-Derived , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Disease Progression , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Retrospective Studies , Vascular Endothelial Growth Factor A/metabolism , Vesicular Transport Proteins/metabolismABSTRACT
Signal transducer and activator of transcription (Stat) 6 is vital to interleukin (IL)-4 and IL-13 responses and the generation of Th2 immunity. We investigated the cellular location of phosphorylated Stat6 and Stat6 DNA binding activity in A201.1 murine B cells and primary splenocytes. Phosphorylated Stat6 was present in cytoplasmic and nuclear extracts from IL-4-treated cells. Confocal microscopy confirmed the presence of phosphorylated Stat6 in the cytoplasm of IL-4-treated cells. In contrast, Stat6 DNA binding activity was present in nuclear extracts, but not in cytoplasmic extracts. Thus, cytoplasmic extracts from IL-4-stimulated cells were devoid of Stat6 DNA binding activity despite the presence of phosphorylated Stat6. Addition of cytoplasmic extracts to nuclear extracts did not inhibit Stat6 DNA binding present in the nuclear extracts. Detergent treatment restored Stat6 DNA binding activity in cytoplasmic extracts of IL-4-stimulated cells. Thus, DNA binding activity of cytoplasmic phosphorylated Stat6 is masked by a factor dissociable by detergent treatment.
