Hölzel Michael, van Diest Paul J, Bier Patrick, Wallisch Michael, Hoatlin Maureen E, Joenje Hans, de Winter Johan P
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
J Pathol. 2003 Oct;201(2):198-203. doi: 10.1002/path.1450.
Fanconi anaemia (FA) is an inherited form of progressive pancytopenia associated with developmental defects, chromosomal instability, and cancer predisposition. At least seven distinct FA proteins function in concert to protect the genome, a key step being the activation of FANCD2 by mono-ubiquitination. This paper reports an immunohistochemical analysis of FANCD2 expression in normal human tissue. The highest expression was observed in maturing spermatocytes and fetal oocytes (consistent with a role for FANCD2 in meiosis) and in germinal centre cells of the spleen, tonsil, and lymph nodes (consistent with a role in proliferation). FANCD2 expression was also seen in tissues predisposed to cancer development in FA patients: haematopoietic cells, especially in the fetus, and squamous cell epithelia, particularly in the head and neck region and uterine cervix. FANCD2 expression was also occasionally seen in the breast and Fallopian tube epithelium, the respiratory epithelium of the trachea, and the exocrine cells of the pancreas, indicating that these tissues may also be cancer-prone in FA. FANCD2 expression is frequently expressed in proliferating cells as demonstrated by Ki-67 immunofluorescence double staining, consistent with a function of FANCD2 in DNA replication.
范可尼贫血（FA）是一种遗传性进行性全血细胞减少症，与发育缺陷、染色体不稳定和癌症易感性相关。至少七种不同的FA蛋白协同作用以保护基因组，关键步骤是通过单泛素化激活FANCD2。本文报道了FANCD2在正常人体组织中的免疫组织化学分析。在成熟的精母细胞和胎儿卵母细胞中观察到最高表达（与FANCD2在减数分裂中的作用一致），以及在脾脏、扁桃体和淋巴结的生发中心细胞中（与增殖作用一致）。在FA患者中易发生癌症的组织中也可见FANCD2表达：造血细胞，尤其是胎儿中的造血细胞，以及鳞状上皮细胞，特别是头颈部区域和子宫颈的鳞状上皮细胞。在乳腺和输卵管上皮、气管的呼吸道上皮以及胰腺的外分泌细胞中也偶尔可见FANCD2表达，表明这些组织在FA中也可能易患癌症。如通过Ki-67免疫荧光双重染色所示，FANCD2表达经常在增殖细胞中表达，这与FANCD2在DNA复制中的功能一致。
