Stoltzfus P, Heselmeyer-Haddad K, Castro J, White N, Silfverswärd C, Sjövall K, Einhorn N, Tryggvason K, Auer G, Ried T, Nordström B
Department of Oncology and Pathology, Karolinska Hospital, 171-76 Stockholm, Sweden.
Int J Gynecol Cancer. 2005 Jan-Feb;15(1):120-6. doi: 10.1111/j.1048-891X.2005.15012.x.
The aim was to determine whether specific gains of chromosome 3q and laminin-5gamma2-chain expression can improve early detection of invasive capacity in precancerous and squamous cell carcinoma of the vulva (VSCC). Six VSCC and three precancerous lesions were studied. Multicolor fluorescence in situ hybridization (FISH) probe sets were applied to nuclei suspensions prepared from archival material using the Hedley method. The probe panel consists of the centromers of chromosome 7, chromosome 3, and the TERC gene residing on the long arm of chromosome 3. Laminin-5gamma2-chain immunohistochemical analysis was performed on corresponding specimens and was expressed only in the VSCC. The genome-specific FISH analysis revealed 3q amplification in 43% of the nuclei analyzed for the VSCC and 22% of the nuclei for the precancerous lesions. Low-level 3q amplifications were found in precancerous lesions with an average fold increase of 1.15 for 3q. The invasive lesions showed higher average fold increases for 3q, averaging 1.32. Laminin-5gamma2-chain protein was expressed only in VSCC, whereas 3q gains were observed both in precancerous lesions and in VSCC, indicating that gain of chromosome 3q is an early and consistent event during carcinogenesis of VSCC.
目的是确定3号染色体q臂的特定增益以及层粘连蛋白-5γ2链的表达是否能改善外阴癌前病变和鳞状细胞癌(VSCC)侵袭能力的早期检测。研究了6例VSCC和3例癌前病变。采用Hedley法将多色荧光原位杂交(FISH)探针组应用于从存档材料制备的细胞核悬液。探针组由7号染色体、3号染色体的着丝粒以及位于3号染色体长臂上的TERC基因组成。对相应标本进行层粘连蛋白-5γ2链免疫组织化学分析,结果显示其仅在VSCC中表达。基因组特异性FISH分析显示,在分析的VSCC细胞核中有43%存在3q扩增,癌前病变细胞核中有22%存在3q扩增。在癌前病变中发现低水平的3q扩增,3q的平均增加倍数为1.15。侵袭性病变显示3q的平均增加倍数更高,平均为1.32。层粘连蛋白-5γ2链蛋白仅在VSCC中表达,而在癌前病变和VSCC中均观察到3q增益,这表明3号染色体q臂增益是VSCC癌变过程中的一个早期且一致的事件。