Primary Pancreatic Adenocarcinoma, Metastatic Lymph Node and Distant Metastasis May Differ in HER2 Expression, Gene Amplification and CEP17 Copy Number: Possible Implications for Diagnostic Evaluation and Therapy.
Franco Fedeli, Simona Boccardo, Paola Ferro, Nader Gorji, Paolo Dessanti, Maria Cristiana Franceschini, Mauro Truini, Maria Pia Pistillo, Sandra Salvi, Silvio Roncella. ASL5, La Spezia, Italy; IST, Genova, Italy; AIL "Francesca Lanzone", La Spezia, Italy
Background: Pancreatic adenocarcinoma (PAC) remains an often incurable disease. The development of the new therapy with anti-p185HER-2 (p185) monoclonal antibodies (Trastuzumab, Pertuzumab) has been proposed although the status of HER2 gene in PAC and its correlation with clinical history remain not completely defined. In our study we evaluated the expression of p185, HER2 gene amplification and chromosome 17 centromere (CEP17) copy number in PAC. In addition, we compared p185 expression and HER2 gene status of primary PAC, matched lymph node (LN) and unmatched distant metastasis (MTS).
Design: We analyzed 83 PAC (26 tumours at initial diagnosis, 20 LN, 37 MTS). On paraffin-embedded tissues, we performed immunohistochemistry (IHC) using the PATHWAY kit by Benchmark XT system (Ventana). The samples were analysed using standard criteria for HER2 positivity. A score of 0 or 1+ was regarded as IHC negative and 2+ or 3+ as IHC positive. FISH, to evaluate HER2 gene amplification and CEP17 copy number, was performed using the Pathvision® (Abbot) and/or ZytoLight kit (ZytoVision).
Results: We found p185 positive expression in 13/83 (15.7%) (all with 2+ score), gene amplification in 4/83 (4.8%) and increased CEP17 in 11/83 (13.2%) of all tissues. In particular, p185 expression was found in 4/4 (100%) cases of HER2 gene amplified tumours, in 4/11 (36.4%) cases of those with increased CEP17, in addition to 1/26 (3.8%) of primary PAC, 1/20 (5.0%) of LN and 11/37 (29.7%) of MTS. HER2 gene amplification was restricted to 4/37 (10.8%) of MTS, whereas increased CEP17 was found only in 8/37 (21.6%) of MTS and in 3/20 (15.0%) of LN. In 3 cases, increased CEP17 was found in LN and not in related primary tumours.
Conclusions: In PAC, p185 positive expression is associated with HER-2 gene amplification but is present only in a set of tumours with increased CEP17. The different HER2 expression observed among primary PAC, LN and distant MTS suggests the need for the pathologist's evaluation of HER2 status in all three tissue samples, as it may cause different responses to HER2 target therapy.
Category: Liver & Pancreas
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 202, Tuesday Afternoon