Nijhuis E R, Nijman H W, Oien K A, Bell A, ten Hoor K A, Reesink-Peters N, Boezen H M, Hollema H, van der Zee A G J
Department of Gynecological Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
J Clin Pathol. 2007 Jul;60(7):824-30. doi: 10.1136/jcp.2005.036038.
Loss of mismatch repair (MMR) gene expression has been associated with fewer metastases and improved prognosis in various tumour types.
To evaluate the predictive and prognostic significance of loss of MMR protein MSH2 in early stage cervical cancer.
Specimens from 218 consecutive patients with early stage, surgically treated cervical cancer were analysed. Median age was 42 years (interquartile range 35-53). International Federation of Gynecology and Obstetrics (FIGO) stages were IB1 (57%), IB2 (25%) and IIA (18%). Histology was 70% squamous cell, 6% adenosquamous and 24% adenocarcinoma. Pelvic lymph node metastasis was present in 66 (30%) patients. Median follow-up was 5.2 years (interquartile range 2.5-7.9). Tissue microarrays (TMAs) were constructed containing three cores of paraffin-embedded tumour per case. MSH2 expression was assessed by immunohistochemistry on TMAs and full sections.
In TMAs MSH2 expression could be analysed in 184/218 (84%) tumours. Loss of MSH2 was observed in 58/184 (32%) tumours, with a moderately strong concordance between TMAs and full sections (kappa = 0.47). In tumours with loss of MSH2, pelvic lymph node metastasis and cancer invasion beyond 10 mm were more frequent (48% vs 25%, and 59% vs 37%, respectively). However, loss of MSH2 expression was not related to recurrence or survival.
TMAs are powerful tools for high throughput screening of biological markers for prognostic value in cervical cancer. Absence of MSH2 expression is associated with a high-risk profile in early stage cervical cancer, but does not predict lymph node status with sufficient accuracy to be used in the clinic.
错配修复（MMR）基因表达缺失与多种肿瘤类型转移减少及预后改善相关。
评估MMR蛋白MSH2缺失在早期宫颈癌中的预测和预后意义。
分析218例连续接受手术治疗的早期宫颈癌患者的标本。中位年龄为42岁（四分位间距35 - 53岁）。国际妇产科联盟（FIGO）分期为IB1期（57%）、IB2期（25%）和IIA期（18%）。组织学类型为鳞状细胞癌70%、腺鳞癌6%和腺癌24%。66例（30%）患者存在盆腔淋巴结转移。中位随访时间为5.2年（四分位间距2.5 - 7.9年）。构建组织微阵列（TMA），每例包含三个石蜡包埋肿瘤核心。通过免疫组化在TMA和完整切片上评估MSH2表达。
在TMA中，184/218（84%）例肿瘤可分析MSH2表达。58/184（32%）例肿瘤观察到MSH2缺失，TMA与完整切片之间有中度强一致性（kappa = 0.47）。在MSH2缺失的肿瘤中，盆腔淋巴结转移和癌浸润超过10 mm更常见（分别为48%对25%，59%对37%）。然而，MSH2表达缺失与复发或生存无关。
TMA是高通量筛选宫颈癌预后生物学标志物的有力工具。MSH2表达缺失与早期宫颈癌的高风险特征相关，但不能准确预测淋巴结状态以供临床使用。
