Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer.
Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer.
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DOI：
10.1186/bcr2719
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Dowsett M
中科院分区：
文献类型：
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作者：
Pinhel IF;Macneill FA;Hills MJ;Salter J;Detre S;A'hern R;Nerurkar A;Osin P;Smith IE;Dowsett M
很少有研究调查手术切除和组织固定之间的时间间隔或核心切割和切除活检之间的差异是否会影响化学测量的生物标志物，包括原发性乳腺癌中的磷酸化蛋白。本研究的目的是确定常见生物标志物的免疫反应性差异，这些差异可能发生在（1）手术中的组织处理结果和（2）核心切割和切除的肿瘤之间。将切除后即刻（样品A）和切除肿瘤常规X射线后（样品B）从手术乳腺癌标本中取出的核心切片福尔马林固定并石蜡包埋，并与常规固定的切除标本（样品C）进行比较。检测Ki 67、雌激素受体（ER）、孕激素受体（PgR）、人表皮生长因子2（HER 2）、p-Akt和p-Erk 1/2的免疫组化表达变化。有21个具有足够肿瘤的组织集可用。采集核心切割物A和B之间的中位时间为30分钟（范围：20 - 80分钟）。样品A和B之间没有标记物显示出显着差异。同样，Ki 67、ER、PgR和HER 2在核心切口和主要切除标本之间没有显著差异，尽管ER的切除值有降低的趋势（P = 0.06）。然而，切除组p-Akt和p-Erk 1/2明显低于核心切除组（中位数分别为27与101和69与193;均P < 0.0001 [双侧]）。乳腺切除术标本中p-Erk 1/2的差异显著大于肿块切除术标本中的差异（P = 0.01）。切除标本术后X线检查后进行的核心切口中的固定延迟对Ki 67、ER、PgR、HER 2、p-Akt或p-Erk 1/2的表达无显著影响。然而，在切除标本的常规固定过程中，可能会发生磷酸化染色的极度损失。这些差异可能归因于次优固定，并可能对涉及这些标记物的临床研究产生重大影响。
Very few studies have investigated whether the time elapsed between surgical resection and tissue fixation or the difference between core-cut and excision biopsies impact on immunohistochemically measured biomarkers, including phosphorylated proteins in primary breast cancer. The aim of this study was to characterise the differences in immunoreactivity of common biomarkers that may occur (1) as a result of tissue handling at surgery and (2) between core-cuts and resected tumours. Core-cuts taken from surgical breast cancer specimens immediately after resection (sample A) and after routine X-ray of the excised tumour (sample B) were formalin-fixed and paraffin-embedded and compared with the routinely fixed resection specimen (sample C). The variation in immunohistochemical expression of Ki67, oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor 2 (HER2), p-Akt and p-Erk1/2 were investigated. Twenty-one tissue sets with adequate tumour were available. Median time between collection of core-cuts A and B was 30 minutes (range, 20 to 80 minutes). None of the markers showed significant differences between samples A and B. Similarly, Ki67, ER, PgR and HER2 did not differ significantly between core-cuts and main resection specimen, although there was a trend for lower resection values for ER (P = 0.06). However, p-Akt and p-Erk1/2 were markedly lower in resections than core-cuts (median, 27 versus 101 and 69 versus 193, respectively; both P < 0.0001 [two-sided]). This difference was significantly greater in mastectomy than in lumpectomy specimens for p-Erk1/2 (P = 0.01). The delay in fixation in core-cuts taken after postoperative X-ray of resection specimens has no significant impact on expression of Ki67, ER, PgR, HER2, p-Akt or p-Erk1/2. However, extreme loss of phospho-staining can occur during routine fixation of resection specimens. These differences are likely attributable to suboptimal fixation and may have major repercussions for clinical research involving these markers.