[625] Loss of Neutrophil Gelatinase Associated Lipocalin (NGAL) Expression in Esophageal Adenocarcinoma (EAC) Is Associated with Higher Pathologic Stage and Poor Survival
DM Maru, AM Correa, Z Tong, H Wang, TT Wu, L Corley, S Krishnan, JA Ajani, SG Swisher, A Rashid, WL Hofstetter, S Guha. The University of Texas MD Anderson Cancer Center, Houston; Mayo Clinic, Rochester
Background: NGAL is a glycoprotein which modifies genes important in cellular differentiation and shown to be abnormally expressed in colon and pancreatic carcinomas and has not been studied in EAC.
Design: Tissue microarray (TMA) from resection specimens of 118 patients (1986-1998) with clinically localized esophageal adenocarcinoma who underwent esophagectomy without preoperative adjuvant therapy were studied. Normal squamous and gastric mucosa (n=5) were used as control. Immunostain for NGAL was performed (monoclonal Ab, Assay Designs, USA) on the TMA following antigen retrieval and blocking of endogenous peroxidase activity. The staining analysis was performed by the Ariol Automated Digital Imaging System (Genetix Limited,UK). A computer software was used to derive quantitative measures of tissue area of chromogen staining and staining intensity. We considered the number of positive tumor cells with any staining intensity. We graded the immunohistochemical stains as grade 1, <10%; grade 2, 10-25%; grade 3, 25-50%; and grade 4, >50%; of the cells in the total area. The staining grades were compared with different pathologic parameters and survival outcome.
Results: The study included 107 men and 11 women with average age of 63 years. All controls specimens showed grade 4 staining intensity. Table shows the correlation of NGAL expression with pathologic parameters and survival.
| Characateristics | NGAL Grade 1 | NGAL Grade 2 | NGAL Grade 3 | NGAL Grade 4 | p value |
| Tumor Differentiation | 0.106 | ||||
| Well (n=5) | 1 | 0 | 1 | 3 | |
| Moderate (n=49) | 15 | 9 | 6 | 19 | |
| Poor (60) | 30 | 9 | 9 | 12 | |
| Location | 0.02 | ||||
| Upper/Mid esophagus (n=6) | 1 | 3 | 2 | 0 | |
| Lower Esophagus (n=112) | 46 | 16 | 15 | 35 | |
| pT stage | 0.001 | ||||
| T1/T2 (n=14) | 1 | 1 | 1 | 11 | |
| T3/T4 (n=104) | 46 | 18 | 16 | 24 | |
| pN stage | 0.000 | ||||
| N0 (n=31) | 1 | 0 | 3 | 27 | |
| N1(n=87) | 46 | 19 | 14 | 8 | |
| pM stage | 0.002 | ||||
| M0 (n=100) | 34 | 16 | 15 | 35 | |
| M1 (n=18) | 13 | 3 | 2 | 0 | |
| Overall Survival(months) | 0.000 | ||||
Mean SD (n=118) | 20.433.7 | 18.343.8 | 22.15 5.5 | 84.11 12.25 | |
| Median (n=118) | 12.87 | 11.03 | 15.03 | 60.33 | |
| Recurrence | 0.018 | ||||
| No (n=55) | 19 | 6 | 6 | 24 | |
| Yes (n=63) | 28 | 13 | 11 | 11 |
Conclusions: This study of large cohort of uniformly treated patients with EAC demonstrates loss of NGAL expression is a marker of aggressive behavior in EAC.
Category: Gastrointestinal
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 92, Wednesday Afternoon