Immunohistochemical MYC protein expression in the different histological grades of follicular lymphoma.

Pel, R. van (Roel) (2014) Immunohistochemical MYC protein expression in the different histological grades of follicular lymphoma. thesis, Medicine.

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Abstract

Background: Follicular lymphoma (FL) is the second most occurring Non-Hodgkin lymphoma. FL is subdivided into the different histological grades 1 - 3B. Normally the course of FL is indolent but sometimes it may undergo transformation into a more aggressive type of lymphoma (tFL). Amongst other genes, MYC alterations may play an important role in this transformation. Until recently, MYC alterations could only be detected with the expensive techniques of karyotyping or FISH. A reliable commercial antibody came available that can detect MYC protein expression with the cheaper and easier to perform technique of immunohistochemistry (IHC). Objective: We wanted to determine if MYC-IHC was suitable to analyse FL and if there was a difference in MYC protein expression in the different grades of FL as well as before and after transformation. Besides that we wanted to assess its potential clinical value by analysing survival after dichotomisation of MYC-IHC expression scores. Materials & methods: Patients were selected from the database of the Haematology department of the UMCG were divided into 4 cohorts according to their histological grade; IHC was performed for MYC protein expression. If possible, paired cases before and after transformation were included. Stained slides were digitalised and quantification of expression was done with the grid-point method. 5 representative areas were selected and a grid was projected over each area. On the intersections of these grids, nuclear staining was scored positive or negative. Slides with Bukitt lymphoma and benign tonsils were included as controls. Results: All included samples were suitable for quantification and a standard error <2% was reached for all samples. In total 111 samples of FL or tFL were included in this study. Fortysix cases of FL grade 1/2 without transformation had a median expression score of 4.0%, 11 cases of FL grade 3A had a median expression score of 14.0%, and 4 cases of FL grade 3B had a median expression score of 26.5%. In addition 21 paired cases of FL ! and tFL were included as well as 8 tFL without its prior indolent FL. Median expression in the paired cases was 6.0% before transformation and 54.0% after transformation. Expression of FL 1/2 was significantly lower than in FL 3A/B (P=0.002) and expression in FL 3A/B was significantly lower than in tFL (P=0.002). FL 1/2 with transformation had significant higher expression than FL 1/2 without transformation (P=0.03). After dichotomisation, MYC-IHC appeared an indicator for survival in FL 1/2 but not in tFL. Conclusion: This study shows that MYC-IHC can be reliably performed and rises significantly with each grade of disease. This may represent a further step in understanding the pathogenesis of FL and transformation. Overall survival is influenced by MYC-IHC score in FL grade 1/2. More clinical significance can be obtained by future research where the results will be validated with FISH.

Item Type:	Thesis (Thesis)
Supervisor name:	Kluin-Nelemans, Prof. dr. J.C. and Kluin, Prof. dr. P.M. and Aukema, S.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:49
Last Modified:	25 Jun 2020 10:49
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/984

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