A. Bain1, A. Vachani6, P. Low7, S. Singhal4, C. Deshpande5 6Perelman School Of Medicine At The University Of Pennsylvania,Department Of Medicine,Philadelphia, PA, USA 1Perelman School Of Medicine At The University Of Pennsylvania,Philadelphia, PA, USA 4Perelman School Of Medicine At The University Of Pennsylvania,Department Of Surgery,Philadelphia, PA, USA 5Perelman School Of Medicine At The University Of Pennsylvania,Department Of Pathology,Philadelphia, PA, USA 7Purdue University,Department Of Chemistry,West Lafayette, IN, USA
Introduction: This study was undertaken in order to better elucidate the relationship between Folate Receptor Beta (FRβ) positive macrophages and cancer prognosis. Tumor associated macrophages (TAMs) play a key role in promoting inflammation and regulating the immune response to malignancies. FRβ is a useful target because its expression is limited to activated macrophages in a subset of disease conditions, including neoplasms. While previous work has suggested a relationship between FRβ+ macrophages and cancer prognosis, to our knowledge no such studies exist for lung adenocarcinoma.
Methods: 69 patients underwent resection for primary lung adenocarcinoma from 2003-2006. Under IRB approved protocol, a tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded specimens from patient tumors. A TMA section was stained using FRβ-specific monoclonal antibody m909 in antibody diluent (1:100). Cytoplasmic staining was measured for FRβ+ macrophage frequency and staining intensity. Samples were scored as 0, no staining; 1+, weak; 2+, moderate; and 3+, strong. Average scores for patients with ≥2 scored TMA tumor cores (n=50) were included in the analysis. An unweighted product score was derived from the frequency and intensity scores to yield a total score of 0-9. Clinical measures including tumor staging and survival status were followed for a minimum of 4 years. The relationship between FRβ expression and survival time was tested using a student's t-test, and differences of tumor staging and survival times were compared by one-way ANOVA. Statistical analyses were done with Stata 13 (StataCorp., College Station, TX).
Results: 37 patient TMA cores had FRβ product scores ≥4, and 29 patients had product scores ≥6. The difference in mean survival time for patients with product scores ≥6 (1750.8 days) and patients with product scores <6 (1417.0 days) was 333.8 days (p-value = 0.0493). Among deceased patients, mean survival time for the ≥6 group (1121.1 days) was greater than for the <6 group (901.5 days). The difference in mean survival time between patients with Stage I/II disease and Stage III disease was 257.0 days (p-value = 0.1588). The relationship between tumor stage and FRβ expression was not statistically significant (Fisher’s exact, p-value = 0.180).
Conclusion: Previous clinical studies have suggested that FRβ expression is limited to M2 macrophages and is associated with poor outcomes. However, our results indicate that FRβ expression may be associated with longer survival times in patients with lung adenocarcinoma. FRβ expression was also a better prognostic indicator of survival time than tumor stage alone.
