Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis.

BACKGROUND: Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Additionally, their prognostic and predictive value in different molecular subtypes of breast cancer is still controversial. The aim of our meta-analysis was to assess the prognostic and predictive value of TILs in different molecular subtypes of breast cancer by summarizing all relevant studies performing multivariate analysis. METHODS: PubMed, Embase, EBSCO, ScienceDirect, the Cochrane Database and Web of Science were comprehensively searched (until March 2020). Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect measures to perform our meta-analysis. A random effect model was used. Stata software, version 15 (2017) (StataCorp, College Station, TX, USA) was used to perform the statistical analysis. RESULTS: Thirty-three studies including 18,170 eligible breast cancer patients were analysed. The meta-analysis showed that high TIL expression was significantly associated with increased pathological complete response (pCR) rates after neoadjuvant chemotherapy in patients with the HER2-enriched molecular subtype (OR = 1.137, 95% CI [1.061 ~ 1.218], p < 0.001) and triple-negative breast cancer (TNBC) subtype (OR = 1.120, 95% CI [1.061 ~ 1.182], p < 0.001). However, high TIL expression was not significantly associated with high pCR rates after neoadjuvant chemotherapy in patients with the luminal molecular subtype of breast cancer (OR = 1.154, 95% CI [0.789 ~ 1.690], p = 0.460). We carried out a meta-analysis on the HRs of overall survival (OS) and disease-free survival (DFS) to assess the prognostic value of TILs in breast cancer with different molecular subtypes more deeply. Our meta-analysis confirmed that high TILs were associated with significantly improved DFS in patients with the HER2-enriched molecular subtype [HR = 0.940, 95% CI (0.903 ~ 0.979), p = 0.003] and TNBC molecular subtype [HR = 0.907, 95% CI (0.862 ~ 0.954), p < 0.001]. However, high TILs were not associated with significantly better DFS in patients with the luminal molecular subtype of breast cancer [HR = 0.998, 95% CI (0.977 ~ 1.019), p = 0.840]. Furthermore, the results confirmed that high TILs were significantly related to better OS in patients with the HER2-enriched molecular subtype [HR = 0.910, 95% CI (0.866 ~ 0.957), p < 0.001] and TNBC molecular subtype [HR = 0.869, 95% CI (0.836 ~ 0.904), p < 0.001]. Conversely, the summarized results indicated that high TILs were significantly associated with poor OS in patients with the luminal molecular subtype of breast cancer [HR = 1.077, 95% CI (1.016 ~ 1.141), p = 0.012]. CONCLUSIONS: Our meta-analysis confirms that high TILs are associated with favourable survival and predicts pCR in breast cancer patients with the TNBC and HER2-enriched molecular subtypes.

ILEI: a novel marker for epithelial-mesenchymal transition and poor prognosis in colorectal cancer.

AIMS: Accumulating evidence over the past decade has shown that abnormal activation of epithelial to mesenchymal transition (EMT) contributes to tumour progression and metastasis in colorectal cancer (CRC). In this study, we investigated the expression of interleukin-like EMT inducer (ILEI) and EMT-associated markers (E-cadherin, vimentin) in CRC tissues and determined the correlations between ILEI expression and clinicopathological characteristics, prognosis and EMT in CRC. METHODS AND RESULTS: In total, 194 patients diagnosed with CRC based on histopathological evaluation and those subjected to surgical resection at the First Hospital of China Medical University between 2003 and 2005 were examined. Immunohistochemical staining for ILEI, vimentin and E-cadherin was performed for each specimen. Cytoplasmic overexpression of ILEI usually accompanied down-regulation of E-cadherin and positive expression of vimentin. Conversely, ILEI was simultaneously down-regulated with overexpression of E-cadherin and negative expression of vimentin. ILEI overexpression was associated significantly with T-stage, N-stage, TNM stage and EMT phenotype (P = 0.024, <0.001, <0.001 and <0.001, respectively). Multivariate analysis revealed that ILEI expression was an independent prognostic factor for patient survival. CONCLUSIONS: Our findings indicate that cytoplasmic ILEI expression is a potential marker of EMT and tumour progression in CRC. ILEI is an independent predictive factor associated with poor prognosis in CRC.

Differential ß-catenin expression levels are associated with morphological features and prognosis of colorectal cancer.

ß-catenin, an epithelial-mesenchymal transition (EMT)-associated marker, is key in the progression of colorectal cancer (CRC). However, the prognostic significance of ß-catenin expression in patients with CRC remains controversial. In the present study, the expression of ß-catenin at the tumor invasive front and the tumor center was investigated, and the correlations amongst ß-catenin differential expression patterns and the clinicopathological characteristics and prognosis of CRC patients were determined. In total, 181 patients that were diagnosed with CRC (as determined by histopathological evaluation) and subjected to surgical resection at the First Hospital of China Medical University between 2000 and 2001 were examined, and CRC specimens were obtained. Immunohistochemical (IHC) staining of ß-catenin was performed for each specimen. The nuclear ß-catenin expression levels were identified to be significantly lower in the tumor center than at the tumor invasive front (immunoreactivity score, 0.05±0.303 versus 2.18±3.917; P<0.001). The presence of nuclear ß-catenin overexpression at the tumor invasive front was found to be correlated with the tumor, node, metastasis stage (P=0.020), lymph node metastasis (P=0.016) and histological differentiation (P=0.006). Survival analysis revealed that reduced membranous expression levels and increased nuclear expression levels of ß-catenin were statistically significantly associated with poor survival times. Furthermore, differential ß-catenin expression levels were associated with aggressive morphological features, EMT and a poor prognosis in CRC. Therefore, IHC analysis of ß-catenin is considered to be a useful marker to predict the prognosis in patients with CRC.

Distribution characteristics of rare earth elements in children's scalp hair from a rare earths mining area in southern China.

In order to demonstrate the validity of using scalp hair rare earth elements (REEs) content as a biomarker of human REEs exposure, data were collected on REEs exposure levels from children aged 11-15 years old and living in an ion-adsorptive type light REEs (LREEs) mining and surrounding areas in southern China. Sixty scalp hair samples were analyzed by ICP-MS for 16 REEs (La Lu, Y and Sc). Sixteen REEs contents in the samples from the mining area (e.g., range: La: 0.14-6.93 microg/g; Nd: 0.09-5.27 microg/g; Gd: 12.2-645.6ng/g; Lu: 0.2-13.3 ng/g; Y: 0.03-1.27 microg/g; Sc: 0.05-0.30 microg/g) were significantly higher than those from the reference area (range: La: 0.04-0.40 microg/g; Nd: 0.04-0.32 microg/g; Gd: 8.3-64.6 ng/g; Lu: 0.4-3.3ng/g; Y: 0.03-0.29 microg/g; Sc: 0.11-0.36 microg/g) and even much higher than those published in the literature. The distribution pattern of REEs in scalp hair from the mining area was very similar to that of REEs in the mine and the atmosphere shrouding that area. In conclusion, the scalp hair REEs contents may indicate not only quantitatively but also qualitatively (distribution pattern) the absorption of REEs from environmental exposure into human body. The children living in this mining area should be regarded as a high-risk group with REEs (especially LREEs) exposure, and their health status should be examined from a REEs health risk assessment perspective.