Risinger John I, Chandramouli G V R, Maxwell G Larry, Litzi Tracy, Berchuck Andrew, Umar Asad
Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Cancer Biomark. 2006;2(1-2):61-8. doi: 10.3233/cbm-2006-21-207.
Microsatellite instability (MSI) is seen in many cancers and is the result of either a germline or somatic defect in the DNA mismatch repair system. Microsatellite instability is common in endometrial cancers occurring in about 25% of cases with endometrioid histology. Tumor infiltrating lymphocytes (TIL) are more prominent in colorectal cancer cases with MSI. The presence of increased TIL is associated with increased survival in these colorectal cancers, and is suggested as one possible mechanism to explain the increased survival rates in colorectal cancer patients with MSI positive cancers. Some degree of evidence indicates that increased TIL is also predictive of increased survival in endometrial cancer. The relative levels and states of activation of TIL in endometrial cancers with and without MSI has not been explored. Our previous data indicates that global gene expression patterns from MSI and non-MSI endometrial cancers are distinct, however TIL markers were not over-represented on statistically relevant gene lists that distinguish these groups. We further examined these pre-existing microarray data by directly querying transcripts present in the T-cell gene ontology (GO) group. No significant differences were observed between MSI and microsatellite stable (MSS) groups. Finally we directly examined a set of T-cell marker transcripts previously utilized to define increased activated and cytotoxic TIL in MSI positive colorectal cancers. Whereas colorectal cancers with MSI have been previously demonstrated to contain higher ratios of CD8/CD3 message levels we observed no difference in endometrial cancers. In addition, levels of CD3 indicated no increases in TIL in MSI positive cases and 2 markers of activation, granzyme B and IL-2R were not different in MSI positive and negative cancers. These data indicate that significant differences in TIL derived transcripts do not occur between endometrioid endometrial cancers with and without microsatellite instability.
微卫星不稳定性(MSI)在许多癌症中都有出现,是DNA错配修复系统中种系或体细胞缺陷的结果。微卫星不稳定性在子宫内膜癌中很常见,约25%的子宫内膜样组织学病例会出现。肿瘤浸润淋巴细胞(TIL)在微卫星不稳定性的结直肠癌病例中更为突出。TIL增加与这些结直肠癌患者的生存率提高相关,并被认为是解释微卫星不稳定性阳性癌症的结直肠癌患者生存率提高的一种可能机制。一定程度的证据表明,TIL增加也可预测子宫内膜癌患者生存率的提高。微卫星不稳定性阳性和阴性的子宫内膜癌中TIL的相对水平和激活状态尚未得到研究。我们之前的数据表明,微卫星不稳定性阳性和阴性的子宫内膜癌的整体基因表达模式是不同的,然而,在区分这些组的统计学相关基因列表上,TIL标记并没有过度呈现。我们通过直接查询T细胞基因本体(GO)组中存在的转录本来进一步检查这些预先存在的微阵列数据。微卫星不稳定性阳性组和微卫星稳定(MSS)组之间未观察到显著差异。最后,我们直接检查了一组先前用于定义微卫星不稳定性阳性结直肠癌中激活和细胞毒性TIL增加的T细胞标记转录本。虽然先前已证明微卫星不稳定性阳性的结直肠癌含有更高比例的CD8/CD3信息水平,但我们在子宫内膜癌中未观察到差异。此外,CD3水平表明微卫星不稳定性阳性病例中TIL没有增加,激活标记颗粒酶B和IL-2R在微卫星不稳定性阳性和阴性癌症中没有差异。这些数据表明,微卫星不稳定性阳性和阴性的子宫内膜样子宫内膜癌之间,TIL衍生转录本没有显著差异。