Objective: To examine the expression of Bc1-10 gene in mucosa-associated lymphoid tissue (MALT) lymphomas, atypical lymphatic hyperplasia and reactive lymphatic hyperplasia; as well as to discover novel mutations and their role in clinical diagnosis and pathogenesis of ocular adnexal lymphatic disorders.
Methods: Thirty-one specimens of ocular adnexal lymphoma were obtained from the department of ophthalmology of Shanghai Changzheng hospital, second military medical university during surgery and were preserved in liquid nitrogen immediately after harvesting. The expression of Bc1-10 gene in ocular adnexal specimens was examined by molecular biological methods. The DNA sequences were analyzed by Sanger method and the results were compared with those of the Gene Bank blast to identify novel mutations. The protein expression of mutant Bc1-10 and NF-kappaB in these specimens were detected by immunohistological method and immunofluorescence. Confocal microscope was used to observe the colocalization of Bc1-10 and NF-kappaB expressions.
Results: Of the 31 specimens, 14 were positive for Bc1-10, of which 10 showed novel mutations of Bc1-10. One of the four atypical lymphatic hyperplasia specimens was positive for Bc1-10, this mutation was reported by others previously. One of the four reactive lymphatic hyperplasia specimens was positive for Bc1-10. Fourteen (60.8%) of the 23 MALT lymphoma specimens were positive for aberration of Bc1-10, including 6 cases with nuclear expression at moderate intensity and 8 cases with expression in the cytoplasm at weak to moderate intensities. Mutations of Bcl-10 were also expressed in the cytoplasm at moderate intensity in two cases with atypical lymphatic hyperplasia and expressed at moderate intensity in one case with reactive lymphatic hyperplasia. I kappa alpha was expressed diffusely in the cytoplasm in 20 cases, among which co-expression of I kappa alpha and Bcl-10 was present in 14 cases.
Conclusions: Novel mutation of Bc1-10 gene in ocular adnexal MALT lymphoma is detected in Chinese patients. Detection of genetic mutation is consistent with and more sensitive than the pathological diagnosis. It can be used to identify the stage and the quality of the disease even no morphological changes are present for discrimination. It can be used as a sensitive index for early diagnosis.