Neoangiogenesis in Pulmonary Adenocarcinoma: Stratification by Size of Invasive Component
NA Cipriani, Q Arif, R Salgia, AN Husain. The University of Chicago, Chicago
Background: Adenocarcinoma (AdCA) comprises ∼40% of lung cancers, for which stage I-II patients undergo resection with curative intent; however, most patients present with metastatic disease, and prognosis is grim. Increased expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR) imparts a poor prognosis, as does increased CD105 microvascular density. Cases of bronchioloalveolar carcinoma (BAC) with a <5mm invasive AdCA center behave indolently. Those with invasive centers 5-10mm or >10mm behave aggressively. In this study we determined if the size of the invasive component and metastases correlated with angiogenesis.
Design: An IRB-approved 18-year retrospective search of our database identified 55 lung resection specimens with combined AdCA and BAC. Of non-metastatic cases, the largest diameter of the invasive AdCA component was measured, and cases were sub-categorized as <5mm, 5-10mm, or >10mm. Microarrays were created, including invasive center, peripheral BAC, uninvolved lung, and in metastatic cases, positive lymph node. Arrays were stained with H&E to verify histology of each 1 mm core and with immunohistochemical (IHC) stains VEGFR2, VEGFR2-3, and CD105. The intensity and distribution of each IHC stain for each core was graded and statistical analyses were performed.
Results: Both the invasive AdCA and BAC components of all tumors showed increasing VEGFR2 staining with increasing diameter of invasive center, with highest staining in metastatic tumors (p=<0.001 to 0.65). In metastatic tumors, there was no difference between the primary AdCA and its corresponding metastases. Within each group, there was no significant difference between the invasive AdCA and the BAC components. Staining for VEGFR2-3 demonstrated a slight trend toward increased expression with increasing diameter of invasive center, but to a lesser degree. CD105 staining was not statistically significantly different.
Conclusions: The expression of VEGFR2 in lung AdCA with BAC increases as the size of the invasive center increases, with the highest expression in metastatic tumors. This finding supports use of antiangiogenic drugs in AdCA, and suggests that the size of the invasive component may be a predictor of response to targeted therapy. The similar expression of VEGRF2 in primary and metastatic AdCA also suggests that tumor at both sites would be responsive to antiangiogenic agents.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 231, Monday Morning