Buch H N, Raskauskiene D, Bahar A, Bicknell E J, Farrell W E, Clayton R N
Centre for Cell and Molecular Medicine, School of Post-Graduate Medicine, Keele University, North Staffordshire Hospital, Stoke-on-Trent, UK.
Clin Endocrinol (Oxf). 2004 Jul;61(1):19-25. doi: 10.1111/j.1365-2265.2004.02046.x.
Postsurgical regrowth or recurrence of nonfunctioning pituitary adenomas (NFAs) is not uncommon and often requires further surgery or radiotherapy (DXT). Routine postoperative DXT increases the incidence of hypopituitarism, which is associated with increased morbidity and mortality. Identification of genetic abnormalities in the tumour tissue, which can predict recurrence, may allow targeting DXT to the most appropriate patients.
We have performed loss of heterozygosity (LOH) analysis on 96 NFAs of which 43 (45%) were recurrent and 53 (55%) were nonrecurrent tumours. Analysis of all tumours was performed on the surgical specimen obtained at the time of first surgery. All tumours underwent allelotyping across nine highly informative microsatellite markers selected on the basis of high LOH frequency in an earlier study involving genome-wide allelotyping. LOH frequency across all microsatellite markers as well as across individual markers was compared between the two cohorts of tumours.
LOH frequency in tumours that subsequently recurred was significantly higher across all microsatellite markers as compared to tumours that did not recur (P < 0.05). Allelic loss across one or more microsatellite marker was significantly higher in recurrent tumours (30/43) as compared to their nonrecurrent counterparts (17/53) (P < 0.01). On Poisson regression analysis, the higher LOH frequency in recurrent tumours was independent of the invasiveness of tumours determined radiologically. In addition, LOH at the microsatellite markers D1S215 and D1S459 was significantly higher in tumours that recurred as compared to tumours that did not (32%vs. 3% and 27%vs. 2%, respectively; P < 0.01 for both). No significant difference in LOH frequency between the two tumour groups was evident at the other markers. No association could be demonstrated between the frequency and pattern of LOH and the time to manifest recurrence.
We have shown that it may be possible to predict recurrence of NFAs by LOH analysis of the initial tumour specimen at predefined microsatellite markers, especially on chromosome 1q. This merits further prospective study.
无功能垂体腺瘤（NFAs）术后复发并不罕见，常需进一步手术或放疗（DXT）。常规术后放疗会增加垂体功能减退的发生率，而垂体功能减退与发病率和死亡率的增加相关。识别肿瘤组织中的基因异常，这些异常可预测复发，可能有助于将放疗靶向至最合适的患者。
我们对96例NFAs进行了杂合性缺失（LOH）分析，其中43例（45%）为复发性肿瘤，53例（55%）为非复发性肿瘤。对所有肿瘤的分析均基于首次手术时获取的手术标本。所有肿瘤均通过对九个高信息微卫星标记进行等位基因分型，这些标记是根据早期一项涉及全基因组等位基因分型的研究中高LOH频率而选择的。比较了两组肿瘤在所有微卫星标记以及各个标记上的LOH频率。
与未复发的肿瘤相比，随后复发的肿瘤在所有微卫星标记上的LOH频率显著更高（P < 0.05）。与非复发性肿瘤（17/53）相比，复发性肿瘤（30/43）中一个或多个微卫星标记的等位基因缺失显著更高（P < 0.01）。经泊松回归分析，复发性肿瘤中较高的LOH频率与通过影像学确定肿瘤的侵袭性无关。此外，与未复发的肿瘤相比，复发肿瘤在微卫星标记D1S215和D1S459上的LOH显著更高（分别为32%对3%和27%对2%；两者P均 < 0.01）。在其他标记上，两组肿瘤的LOH频率无明显差异。LOH的频率和模式与复发显现时间之间未显示出关联。
我们已经表明，通过对初始肿瘤标本在预定义的微卫星标记上进行LOH分析，尤其是在染色体1q上，有可能预测NFAs的复发。这值得进一步的前瞻性研究。
