The Genetic Changes And Prognostic Analysis In Primary Ocular Adnexal Extranodal Marginal Zone Lymphoma Of Mucosa-associated Lymphoid Tissue (MALT Lymphoma)

Objectives:To investigate the genetic changes of three genes which were reported with higher mutation frequency--MALT1, Bcl2, Bcl6in primary ocular adnexa lmucosa-associated lymphoid tissue lymphoma POAL (MALT). Factors affecting its prognosis are also studied, especially a preliminary exploration of the relationship between its genetic abnormality and prognosis.Methods:(1)27cases primary diagnosed with POAL (MALT) were collected from the Pathology Department of Remin Hospital, Wuhan University. Histological evaluation was done based on hematoxylin and eosin stain (H&E). Immunohistological method of En Vision was applied to detect the expression of CD20, CD5, CD23, CD10, Bcl6, CyclinD1, Ki67, Bcl2, muml and P53in all samples and diagnosis was made on its clinical characteristics, morphological changes immunophenotype.(2) Fluorescence in situ Hybridization (FISH) was adopted simultaneously to explore three genetic changes with a higher frequency of mutations---MALT1gene, Bcl-2gene and Bcl6gene.(3) Clinical data were analyzed to reveal the characteristics of patients as to age, gender, location of lesion, clinical stages, therapies and immunophenotype, etc. Meanwhile, the relationship between the genetic abnormalities and its prognosis in POAL (MALT) was further investigated.Results:(1) Morphological features:The tumor cells were small to medium sized, typically with lightly eosin stained cytoplasm, maybe accompanied by plasmacytoid cell differentiation and responsive inflammatory cells infiltration; Tumor cells exhibit diffuse growth, maybe accompanied by some residual lymphoid follicles and follicular implantation formed by invading cells. Immunophenotype:The tumor cells expressed B cell marker such as CD20, while they didn’t express T cell marker such as CD3. The expressions of other B cell markers such as CD5, CD23, CD10, Bcl6, CyclinDl, CD23etc were also negative. The proliferative indexs of Ki67were low. In addition, Bcl2was frequently expressed whereas mum-land P53were not expressed. Based on those clinical, morphological and immunophenotype characteristics, the27cases were diagnosed with POAL (MALT).(2) Fluorescent in Situ Hybridization (FISH):①MALT1gene:It is located in Chromosome18with rearrangement indicating t (14;18)(q32; q21)or t(11;18)(q21; q21) or amplification indicating+18;②Bcl-2gene:It is located in Chromosome18with amplification indicating+18;③Bcl-6gene is located in Chromosome3with amplification indicating+3. In total27cases, the amplification incidence of MALT1gene is14.8%and its ectopic rearrangement incidence is22.2%; the amplification incidence of Bcl-2gene is11.1%and the amplification incidence of Bcl-6is33.3%.(3) The median follow-up time is46months. The overall3-year survival rate and progression-free survival rate of POAL (MALT) are100%and88.9%respectively. The progression-free survival rate shows a negative correlation with age (P=1.000), gender(P=0.545), location of lesion (P=0.596)、genetic change of MALT1(P=1.000), genetic change of Bcl-6(P=1.000), genetic change of Bcl-2(P=0.308), surgical procedures (P=1.000),etc. However, it shows a positive correlation with postoperative treatment (P=0.003).Conclusion:(1) The genetic abnormality exists in the three genes (MALT1、Bcl-2、Bcl-6) in POAL (MALT).(2)The genetic changes in MALT1, Bcl-2and Bcl-6show a negative correlation with prognosis.(3) POAL (MALT) can be treated effectively. Patients with simple surgical resection are liable to relapse. Radiotherapy is a standard care for the disease.