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M.L. Cowan
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-009 - Hepatocyte Growth Factor (HGF) Expression in Malignant Mesothelioma: A Potential Predictive Marker for <em>met/</em>HGF-Targeted Therapy? (ID 2908)
09:30 - 09:30 | Author(s): M.L. Cowan
- Abstract
Background:
Malignant mesothelioma (MM) is an aggressive neoplasm predominantly involving the pleura with less than 2 years median patient survival time and limited systemic therapeutic options. The HGF-MET axis is important in cell proliferation and homeostasis. Dysregulation of the pathway has been linked to tumorigenesis. Met overexpression has been used as a predictor of response to Met-targeted therapy with limited success. HGF is the only known ligand for Met, but intratumoral HGF levels have not been studied in MM. In a preclinical glioblastoma model autocrine signaling by HGF was predictive for Met-Targeted therapy. Our aim was to evaluate HGF expression patterns and to assess the feasibility of non-isotopic bDNA in situ hybridization to reliably detect HGF expression in MM.
Methods:
We analyzed HGF expression using non-isotopic branched-DNA in situ hybridization on an automated platform in 39 samples of MM. In a subset of cases manual in situ hybridization was also performed. Immunohistochemistry for c-met using a rabbit monoclonal antibody and semiquantitative scoring system proposed for NSCLC was also available for 33 tumors. The cohort included 10 peritoneal (3 male and 7 female, age range 15-77; median 64.5) and 29 pleural tumors (24 male and 5 female, age range 24-88; median 67.4). There were 28 epithelioid, 10 biphasic and 1 sarcomatoid tumors. HGF expression was scored as none, weak, moderate or strong (normal placenta and surrounding benign tissue served as controls).
Results:
Moderate to strong HGF expression was seen in 7 cases (6 strong, 1 moderate), weak expression was noted in 10 tumors while 22 were negative. Met IHC was only available for 3 of the 6 strong HGF expressing tumors. Of the 16 met positive tumors only 1 showed strong HGF expression while the majority were HGF negative (10) or weak positive (5). Intratumoral heterogeneity and both paracrine and autocrine HGF expression were also observed. The automated and manual in situ hybridization methods showed concordant results.
Conclusion:
Non-isotopic bDNA assay can be used to reliably detect HGF mRNA in mesothelioma tissue sections. A range of HGF expression levels can be seen with a subset of cases showing moderate to strong (18%) expression. Intratumoral heterogeneity is present and both paracrine and autocrine sources of HGF can be identified. The majority of c-met positive (2+ and 3+) tumors exhibit weak or no HGF expression with only 1 of 3 HGF strongly positive tumor showing positive (2+) c-met staining. Further studies are needed to determine if HGF expression can be used as a predictive marker for c-met/HGF targeted therapy in malignant mesothelioma.
