Wijs, C.J. de (Calvin Jay) (2019) Immunohistochemical Expression of MET in Positive Sentinel Lymph Nodes in Melanoma Patients: a Pilot Study. thesis, Medicine.
Full text available on request.Abstract
Introduction: Melanoma is the 19th most common cancer worldwide and the deadliest form of skin cancer with a rapidly increasing incidence. Melanoma metastasizes early into regional lymph nodes through the lymphatic route, and as a result the sentinel lymph node biopsy (SNB) plays an integral role in diagnosis, disease staging and the prognosis. The current SNB standard of care is the injection of a radioactive tracer followed by lymphoscintigraphy, with or without blue dye injection. In order to find a less invasive SN mapping technique, the use of near-infrared probes identifying the mesenchymal-epithelial transition factor (MET) a proto-oncogene could prove to be a valid alternative. Furthermore, detecting novel tumor markers in the sentinel lymph node (SN) is important as the information retrieved from the primary melanoma up to the SN will be utilized for adjuvant treatment considerations. One potential tumor marker is MET, which could aid in the setup of bespoke treatment strategies. Abnormal activation of MET has been linked with malignant transformations and to an overall worse outcome in melanoma patients. However, no research has evaluated the presence of MET and its potential prognostic value in the SNs of melanoma patients. This study aims to assess the immunohistochemical expression of MET in SNs positive for metastatic melanoma and evaluate the potential diagnostic and prognostic value. Methods: SN samples were randomly identified from cutaneous melanoma patients from the Department of Pathology at the Erasmus MC, Rotterdam between 2000-2016. Data on histopathological information of the primary melanoma and the SN were obtained from the pathology reports. Data on patient characteristics and follow-up were retrieved from electronic patient records. The SN samples were immunohistochemically stained for MET. These samples were regarded as positive for MET when ≥10% of the tumor cells demonstrated immunoreactivity, and the samples were classified as weak/moderate/strong depending on the staining intensity. For baseline characteristics, χ2, Fisher’s exact test, Mann-Whitney U were used when appropriate. Non-parametric correlations were tested by the Spearman’s rank correlation coefficient (ρ). Univariable binary logistic regression analyses determined the associations with clinicopathological factors and positive MET staining. Kaplan-Meier estimates were used to determine the disease-free survival (DFS), melanoma specific survival (MSS), distant metastasis free survival (DMFS) and overall survival (OS) for the tested SN samples. Univariable Cox regression analyses were performed to determine the prognostic value of each variable. Results: Forty-five cases were identified. Thirty-seven SNs were included for further analysis as 6 SNs were not interpretable and 2 had no tissue available. Of the 37 SNs, 24 (65%) were positive for MET of which 17 (74%) had a cytoplasmic and membranous pattern of MET expression. No statistically significant associations were found between the presence of MET and the standard clinicopathological features associated with melanoma. Moreover, Breslow’s depth and SN tumor burden showed no significant correlation with positive MET immunoreactivity (ρ=0.134, P=0.435) and (ρ=-0.77, P=0.655) respectively. Lastly, positive MET immunoreactivity was not prognostic for DFS (HR=1.06 [95%CI 0.44–2.57], P=0.895), MSS (HR=1.31 [95%CI 0.47–3.70), P=0.604), DMFS (HR=2.20 [95%CI 0.63–7.67], P=0.203), and OS (HR=1.53 [95%CI 0.57–4.11], P=0.395). Conclusion: In this study no significant association between the presence of MET in SNs of melanoma patients and the overall prognostic or diagnostic value was found. However, the use of MET as a therapeutic target remains interesting.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Hemmer, P.H.J. |
| Supervisor name: | Mulder, E.E.A.P. and Grünhagen, D.J. and Verhoef, C. |
| Faculty: | Medical Sciences |
| Date Deposited: | 13 Oct 2020 10:54 |
| Last Modified: | 13 Oct 2020 10:54 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2775 |
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