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Use of DPC-4 immunostaining of diagnostic cytology specimens to predict the pattern of tumor progression in locally advanced pancreatic cancer patients (LAPC).

209 Background: An autopsy study has identified DPC-4 as a potential biomarker of the pattern of disease spread in pancreatic cancer patients (Iacobuzio-Donahue et al, JCO, 2009). We sought to determine whether DPC-4 expression determined by immunohistochemistry (IHC) staining of primary tumor cytology specimens correlates with the clinical pattern of progression in patients with locally advanced pancreatic cancer (LAPC).


METHODS
LAPC patients with ECOG 0-1 PS were treated with gemcitabine (1000 mg/m2), oxaliplatin (100 mg/m2), and cetuximab for (500mg/m2) q2wks for 4 doses followed by XRT (50.4 Gy to the gross tumor only) with capecitabine (825 mg/m2 twice daily, days of radiation) and cetuximab on a multiinstitutional trial. Forty-one of 58 patients treated at our institution had cytology specimens suitable for IHC staining. The patterns of progression were determined based on radiographic studies and clinical symptoms. Findings were blinded from the IHC results. Patients were categorized as 1) local disease dominant, 2) distant disease dominant, 3) indeterminate pattern, and 4) no progression. The IHC scoring of DPC-4 was determined by an experienced cytopathologist who was blinded from the clinical data.


RESULTS
Median, 1yr and 3yr actuarial OS are 18.2 months, 67.2% and 18.5%. Dominant progression pattern was local (n=15), distant (n=14), indeterminate (n=8), and no progression (n=4). Intact DPC expression correlated with local dominant progression (11/15) and DPC-4 loss correlated with distant dominant progression (10/14), p=0.016. The median DM free survival rate was 18.0 for intact DPC-4 versus 12.5 mo for DPC-4 loss patients (p=NS). There was no significant difference in overall survival based on DPC-4 status.


CONCLUSIONS
Determination of DPC-4 expression from cytology specimens is feasible. DPC-4 expression correlated with the pattern of progression and is consistent with previous autopsy data. DPC-4 expression does not appear to be predictive or prognostic. Prospective validation of DPC-4 as a biomarker of disease progression is warranted and may lead to personalized treatment strategies for patients with LAPC. [Table: see text].