Abstract 5074: Evaluation of PTEN and TMPRSS2-ERG abnormalities in prostate cancer by FISH and immunohistochemistry to address intra- and inter- tissue heterogeneity and disease progression
Bibliographic record
Abstract
Abstract Background: Gene fusions involving the ERG oncogene and deletions of the PTEN tumor suppressor gene are frequent alterations in prostate cancer. Recent reports highlighted the cooperation of these two pathways in prostate cancer progression using mouse models and human tumors. We recently developed a monoclonal antibody (CPDR ERG-MAb) that specifically recognizes the ERG oncoprotein in human prostate tumors. The objective of this study was to determine the frequency of ERG positive prostate cancer by immunohistochemistry (IHC) compared to ERG gene fusion frequency by fluorescent in situ hybridization (FISH), their association with PTEN deletion, and correlation with clinico-pathological parameters of disease progression. Design: A tissue microarray (TMA) was constructed from 142 radical prostatectomy (RP) specimens with usual acinar-type prostate carcinoma obtained at University Health Network (UHN) between 2001 and 2002 comprising 742 spots. The TMA was constructed using up to six 0.6 mm donor cores from each RP specimen. In cases of multi focal and bilateral carcinoma, 3 donor cores were obtained from the largest foci in each lobe. Different Gleason patterns were also sampled within each focus. Standard clinical follow-up data, representing 7-9 years of follow-up, were compiled for each case using a UHN RP clinical database. Results: Of the 742 cores, analysis was performed in 536 evaluable cores. Concordance between the ERG IHC and TMPRSS2 FISH in this multi-sampled TMA was 71%. Heterogeneity of the PTEN locus was widespread both within tumor foci and between foci. The assay methodology influenced overall results. For example, FISH analysis showed wild type (wt) PTEN and wt ERG in 48% of tumor specimens in comparison to 31% by PTEN FISH and ERG IHC. Higher association of PTEN deletion rate was noted in ERG IHC positive tumors. Of note, higher frequency of homozygous PTEN deletions associated with the ERG IHC positive (5%) tumors in comparison to ERG negative (1.5%) tumors. Conclusions: Comparison of FISH and IHC based assays to analyze ERG alterations in the prostate tumors need continued evaluations in independent studies. PTEN interaction with ERG status may reveal mechanistic insights in disease progression. Further validation studies are needed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5074. doi:10.1158/1538-7445.AM2011-5074
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".