Leeuw, D. (Dianne) (2017) C-Met expression in papillary thyroid carcinoma, a potential target for fluorescence guided surgery? thesis, Medicine.
Full text available on request.Abstract
Recurrence is one of the primary concerns in management of papillary thyroid cancer (PTC). Approximately 50% of the patients will have central lymph node metastases at initial diagnoses which is a risk factor for recurrent disease. The lack of an accurate staging modality to select patients with lymph node metastases for central lymph node dissection (CLND) could be overcome by molecular fluorescence guided surgery (MFGS). A c-Met specific fluorescent tracer EMI-137 has already been developed and could potentially make PTC tissue visible during surgery. In this study, c-Met expression in PTC was investigated by means of immunohistochemistry. Methods A tissue micro array (TMA), containing PTC tissue and normal thyroid tissue was mechanically stained by immunohistochemistry using the c-Met antibody Cell Signalling(8198S). For each patient, an H-score and the main staining intensity (0 to 3+) were determined by two persons. Staining intensities in PTC tissue based on the H-scores were compared to normal thyroid tissue for the whole cohort and in addition for a cohort with matched PTC and adjacent normal thyroid tissues. Sensitivity and specificity for this antibody were calculated based on a main staining intensity cut-off point of >2+ for the whole cohort. Within the matched cohort, sensitivity, specificity, positive and negative predictive value were calculated based on a difference between PTC and normal thyroid tissue of 1+ or more. It was evaluated if a high c-Met expression based on the main staining intensity increases the risk of recurrence over 10 years. C-Met expression, gender, T-stage, tumor size, N-stage, venous invasion, extra-thyroidal spread and the BRAF mutation were investigated as independent predictors of recurrence. Results staining intensities in PTC tissue from 741 patients and normal thyroid tissue from 108 patients were evaluated. Staining intensity was significantly higher in PTC compared to normal thyroid tissue (p<0.001). A sensitivity of 75% and a specificity of 97% were calculated for Cell Signalling(8198S) to distinguish PTC at IHC. Within a matched cohort of 70 patients a sensitivity, specificity, positive and negative predictive value of 79% were calculated. From 465 patients, clinical data were available. Patients with a 3+ main staining intensity have a higher risk of developing recurrence over time. Gender is an independent predictor of recurrence (p=0.008), c-Met expression is not an independent predictor of recurrence (p=0.068). Conclusion Based on staining intensity is concluded that c-Met expression is higher in PTC compared to normal thyroid tissue. A higher c-Met expression increases the risk of recurrence over time, however it is not an independent predictor. For future perspectives, c-Met could be investigated as a potential target for MFGS.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor: and Kruijff Dr. S. MD PhD and Department of Surgical Oncology, University Medical Center G |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:01 |
| Last Modified: | 25 Jun 2020 11:01 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2098 |
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