71 Background: HER2 is overexpressed in 21% of gastric and 33% of GEJ ACA, and pts with advanced HER2pos disease survive longer after chemotherapy and trastuzumab than after chemotherapy alone. This retrospective analysis was undertaken to better define the clinicopathologic features and treatment outcomes in pts with HER2pos ACA of the E and GEJ. Methods: Between 11/99 and 7/06, 156 pts with T3 or N1 or M1a ACA of the E or GEJ were entered on one of two Cleveland Clinic trials. Induction chemoradiation, with 96 hour infusions of cisplatin (20 mg/m2/d) and fluorouracil (1,000 mg/m2/d) beginning on day 1 of radiation (30 Gy at 1.5 Gy bid), was followed by surgery and identical post-operative chemoradiation. 76 pts also received 2 years of oral gefitinib. Pathology was tested for HER2 by immunohistochemistry using PATHWAY anti-HER-2/neu 4B5 rabbit monoclonal primary antibody (Ventana, Tucson AZ) and in situ hybridization with the inform HER2 dual ISH DNA probe cocktail assay (Ventana, Tucson AZ). Baseline characteristics and outcomes after treatment of the HER2pos and negative (neg) pts were compared. Results: Of the 156 pts, 136 pts had either initial biopsy or resection specimen available. HER2 was deemed pos if either was pos. Discordance between biopsy and resection was found in only 6/65 pts (9%). 32 pts (24%) were HER2pos; 27% of 82 pts with GEJ, and 19% of 54 pts with E tumors (p=0.31). There was no statistical difference between HER2pos and neg pts in age, gender, race, stage, or pathological response. The only difference was that HER2neg tumors were more likely poorly differentiated (p<0.001). Locoregional control, distant metastatic control, freedom from recurrence and overall survival were statistically the same in both the entire cohort, and in the gefitinib-treated subset. Conclusions: Except for tumor differentiation, HER2pos and neg pts with ACA of the E and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2pos gastric cancer and the similar incidence of HER2 overexpression in the E and GEJ, further evaluation of HER2 directed therapy in this disease seems indicated. No significant financial relationships to disclose.
Clinicopathologic features and treatment outcomes of patients with fibrillary glomerulonephritis
