PurposeDeregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients.Patients and methodsA total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed.ResultsThe positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (P<0.05). Multivariate analysis established that the high expression of HVEM (P=0.010), depth of invasion (P=0.001), lymph node metastasis (P<0.001), and histological grade (P=0.027) were independent prognostic factors associated with overall survival in patients with gastric cancer.ConclusionThe increased BTLA and HVEM levels correlate with the development and poor prognosis of gastric cancer. HVEM is an important prognostic indicator, and BTLA/HVEM pathway is considered to be a promising candidate for immunotherapy of gastric cancer.

Tumor-associated macrophages (TAMs) have been correlated with increased angiogenesis and poor prognosis in breast cancer. However, the precise role of TAMs in tamoxifen resistance remains unclear. We used immunohistochemical method to examine the expression of epidermal growth factor receptor (EGFR) and CD163+ macrophages in 100 breast cancer tissues. The clinical and biological features of 100 patients were estrogen receptor (ER)-positive and human epidermal growth factor receptor 2(Her-2)-negative tumors. The tamoxifen resistant tissues (n = 48) were the surgical excision samples from patients who developed recurrence or metastasis at the time of adjuvant tamoxifen treatment. The tamoxifen resistant tissues were contrast to tamoxifen sensitive tissues (n = 52). Positive staining for EGFR and CD163+ macrophages were observed in 21 samples (43.8 %) and in 26 samples (54.2 %) respectively in tamoxifen resistance group, which were higher than that of tamoxifen sensitive group (P = 0.001 and P = 0.000279 respectively). Significant positive correlations were found between the expression of EGFR and CD163+ macrophages (r = 0.567, P < 0.01). CD163+ macrophages were positively correlated with tumor size, lymph node metastasis and obesity. Obesity was also related to tamoxifen resistance (P < 0.05). The patients with higher density of CD163+ macrophages infiltration suffered from shorter time to develop recurrence or metastasis (P < 0.05). TAMs may be associated with tamoxifen resistance. Further studies are needed to investigate the potential mechanism between TAMs and tamoxifen resistance.

Several reports have suggested that peripheral blood-based parameters are associated with host immunity response, which is an essential component of the pathogenesis and progression of cancer. The purpose of the present study was to identify the prognostic significance of various peripheral blood-based biomarkers and to determine the optimal cut-off value suitable for luminal breast cancer patients. We found that lymphocyte-to-monocyte ratio (LMR) was significant prognostic predictors. And the patients with a CEF regimen and LMR ratio ≥ 5.2 gained a good prognosis. This study suggested that the LMR could be regarded as an independent prognostic factor in luminal breast cancer patients. The elevated LMR level also had enhanced 5-fluorouracil sensitivity in luminal breast cancer patients.

ObjectiveTo investigate the clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC) for surgery by comparing the difference between PTMC and larger papillary thyroid carcinoma (LPTC).MethodsWe analyzed the differences in the clinicopathological characteristics, prognosis, B-type RAF kinase (BRAF)V600E mutational status and expression of angiogenic factors, including pigment epithelium-derived factor (PEDF), Vascular Endothelial Growth Factor (VEGF), and hypoxia-inducible factor alpha subunit (HIF-1α), between PTMC and LPTC by retrospectively reviewing the records of 251 patients with papillary thyroid carcinoma, 169 with PTMC, and 82 with LPTC (diameter >1 cm).ResultsThere were no significant differences in the gender, age, multifocality, Hashimoto’s thyroiditis, TNM stage, PEDF protein expression, rate of recurrence, or mean follow-up duration between patients with PTMC or LPTC. The prevalence of extrathyroidal invasion (EI), lymph node metastasis (LNM), and BRAF mutation in patients with PTMC was significantly lower than in patients with LPTC. In addition, in PTMC patients with EI and/or LNM and/or positive BRAF (high-risk PTMC patients), the prevalence of extrathyroidal invasion, Hashimoto's disease, lymph node metastasis, tumor TNM stage, PEDF positive protein expression, the rate of recurrent disease, and the mRNA expression of anti-angiogenic factors was almost as high as in patients with larger PTC, but with no significant difference.ConclusionsExtrathyroid invasion, lymph node metastases, and BRAFV600E mutation were the high risk factors of PTMC. PTMC should be considered for the same treatment strategy as LPTC when any of these factors is found. Particularly, PTMC with BRAFV600E gene mutations needed earlier surgical treatment. In addition, the high cell subtype of PTMC with BRAFV600E gene mutation is recommended for total thyroidectomy in primary surgery to reduce the risk of recurrence.

BackgroundMDM4 is the important negative regulator of the tumor suppressor protein p53, which is overexpressed in various human cancers. This study evaluates the MDM4 expression in patients with gastric adenocarcinoma (GTAC) at the mRNA and protein levels and examines relationships among MDM4 expression, clinicopathological features, and prognosis.ResultsThe qRT-PCR and the Western blot analysis showed that the MDM4 expression level was high in GTACN+ but not in GTACN−. The high expression level of MDM4 was significantly associated with age (P = 0.047), lymph node metastasis (LNM) (P < 0.001), pathological stage (P < 0.001), differentiation status (P = 0.001), and preoperative serum CA19-9 level (P < 0.001). Moreover, the survival analysis showed that Borrmann type, depth of invasion, LNM, and preoperative serum CA19-9 level were independent prognostic factors. The univariate analysis revealed that MDM4 expression influenced GTAC prognosis. Furthermore, the influence of overall prognosis relies on whether or not the high MDM4 expression level could lead to LNM.Materials and MethodsWe investigated MDM4 expression in primary GTAC and paired normal gastric tissues (30 pairs) through qRT-PCR and Western blot analyses. We also performed immunohistochemistry analysis on 336 paraffin-embedded GTAC specimens and 33 matched normal specimens.ConclusionsMDM4 expression may result in LMN of GTAC. High MDM4 expression levels are associated with LMN of GTAC and influence the prognosis of patients with GTAC.