HER-2 gene amplification in pancreatic cancer

Introduction: Epidermal growth factor receptor-2 (HER-2) has been implicated in malignant transformation and metastasis formation. In pancreatic cancer HER2 overexpression detected by immunohisto-chemistry varies between 17–82%. The success of HER-2 neutralizing antibodies in breast cancer treatment suggests beneficial effect of this treatment in tumors overexpressing HER-2. However, it is still controversial whether gene amplification or protein detection is required for the initiation of the treatment.

Aim: To correlate HER-2 DNA amplification and protein overexpression in human pancreatic cancer.

Material and methods: DNA was isolated from formalin fixed, paraffin embedded tissue sections of 27 pancreatic adenocarcinomas. Real-time PCR was used to quantify gene amplification. Tissue sections from the identical specimens were used for immunohistochemistry. Gene amplification was analyzed using internal control and classified as positive if the ratio was more than two. Immunostaining was classified 0, 1+, 2+, 3+.

Results: Only one tumor showed 3+ HER-2 positivity and another 1+ positivity analyzed by immunohistochemistry. On the contrary, 12/27 (44%) tumors showed gene amplification detected by real time PCR. The highest levels of DNA amplification corresponded to 3+ and 1+ positivity, respectively.

Conclusion: HER-2 gene amplification data in pancreatic cancers did not correspond with the immunohistochemical detection. In HER2 overexpressing pancreatic carcinomas specific antiHER2 therapy might be useful. Further analysis is required to explain the discrepancy between the results of the methods.

The project was supported by grant NKFP-0023/2002.