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D. Pandya
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-054 - Validation of PTEN and c-MET Status in Small Biopsy Material and Cytology for Pulmonary Adenocarcinoma (ID 2176)
09:30 - 09:30 | Author(s): D. Pandya
- Abstract
Background:
Targeted therapy in lung cancer is an expanding field. Molecular alterations in phosphatase and tensin homolog (PTEN) and c-MET (mesenchymal epithelial transition proto-oncogene) are potential therapeutic targets. Loss of PTEN expression has been associated with activation of PIK3CA/AKT/mTOR pathway and is associated with sensitivity to mTOR inhibitors. Amplification or overexpression of c-MET is associated with resistance to tyrosine kinase inhibitors and/or poor prognosis. Both PTEN and c-MET can be detected by immunohistochemistry. In this study we evaluated the concordance rate of both antibodies in biopsy material and subsequent excision of the same tumor, since small biopsy and cytology material are the only tissue available for diagnosis in patients with advanced stage. In addition since biopsy material is collected in different fixatives, we also compared the antibody expression in alcohol versus formalin fixed tumors.
Methods:
Pathology database was queried for concurrent biopsy and surgical specimens from 12/2010-7/2014. Surgical core biopsies (n=44) and cytology aspiration biopsies (n=10) with surgical specimens were reviewed to evaluate tumor histology and specimen cellularity. In addition, 8 cases of NSCLC were scrapped and collected in formalin and alcohol fixative. Immunohistochemistry with PTEN antibody (clone 138G6) and c-MET antibody (clone sp44) were performed according to manufactures’ instruction following a rigorous validation using positive and negative controls. PTEN staining was evaluated for complete loss of expression or retention (any cytoplasmic or nuclear stain). c-MET staining was evaluated for the intensityand extent of the staining. Positivity is defined as a strong membranous staining (2-3+) in more than 50% of the tumor cells.
Results:
There was a 90% (19/21) concordance for PTEN expression between biopsy and resection (k=0.76). 6 cases showed loss of expression in the biopsy, among these cases 2 were classified as retained PTEN in the excision. In both cases the excision specimen had partial loss of PTEN. Partial loss of PTEN was seen in 3 other cases with retained PTEN in biopsy. There is a 95.2% (20/21) concordance in c-MET staining (k=0.89). In the discrepant case, the biopsy was deemed positive (2+ > 50% of tumor cells), with a negative excision (1+ >70% of tumor cells). For the cases that were fixed in alcohol and formalin there was a 62% (5/8) concordance for PTEN (k=0.37). 3 cases showed loss of expression in alcohol fixed tissue but retention in formalin fixed material. There was a 37% (3/8) concordance for c-MET between the two fixatives (k=0.21). In the 5 discordant cases, c-MET expression was interpreted as negative in alcohol fixed but was considered positive in formalin fixed tissue due to variability in the intensity of staining.
Conclusion:
Despite a good correlation between biopsy and resection for both markers, our results show there is a greater possibility of discrepant results for PTEN than c-MET because of geographic heterogenetic of expression and scoring criteria. The type of fixative (alcohol vs. formalin) is associated with variability in antibody expression. Therefore evaluation of PTEN and c-MET staining in biopsy material and alcohol fixed tissue should be interpreted with caution, especially when designing clinical trials for potential therapy.
