NK- and B-cell infiltration correlates with worse outcome in metastatic ovarian carcinoma

We studied the clinical role of leukocyte infiltration and chemokine receptor expression in ovarian carcinoma effusions. Expression of leukocyte markers (CD3, CD4, CD8, CD4/CD8 ratio, CD16, CD19, and CD14) and chemokine receptors (CXCR1, CXCR4, CCR2, CCR5, and CCR7) was studied in 73 effusions by using flow cytometry. CXCR4, CCR5, and CCR7 were expressed abundantly on leukocytes, but all receptors were expressed rarely on cancer cells. The presence of natural killer cells (P = .042) and International Federation of Gynecology and Obstetrics (FIGO) stage IV disease (P = .024) predicted worse overall survival (OS). A higher percentage of CD19+ cells (P = .015) and stage IV disease (P = .008) predicted poor survival for patients with postchemotherapy effusions. Only FIGO stage retained significance as a predictor of OS (P = .035) in multivariate analysis. Chemokine receptors are expressed widely on leukocytes but rarely on carcinoma cells in ovarian carcinoma effusions, arguing against an autocrine chemokine pathway in this malignancy. Immune response parameters in ovarian cancer effusions are weak predictors of outcome.     

Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma

Recently, the ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma. The prognostic significance of the loss of ARID1A expression is not known. The current study was designed to evaluate whether ARID1A was a prognostic factor for progression, survival, and chemoresistance in ovarian clear cell carcinoma. A total of 60 patients, who were surgically treated for primary ovarian clear cell adenocarcinoma, were enrolled. Surgical specimens were examined for ARID1A protein expression by immunohistochemistry. The correlations between the loss of ARID1A expression and clinicopathological characteristics, prognosis, and chemosensitivity were investigated. Loss of ARID1A expression was identified in 9 (15.0%) of 60 ovarian clear cell carcinoma samples. Loss of ARID1A staining intensity (0+) was more frequently found in cells of clear cell carcinomas than in high-grade serous carcinomas (P<0.01). Loss of ARID1A expression was significantly correlated with advanced FIGO stage and high CA125 levels (P=0.02, 0.01). There were no significant correlations between loss of ARID1A expression and patient age, status of residual tumor, Ki-67 labeling index, or the status of endometriosis. Loss of ARID1A correlated with shorter progression-free survival of patients with clear cell carcinomas treated with platinum-based chemotherapy (P<0.01). Loss of ARID1A expression tended to correlate with shorter overall survival in patients with ovarian clear cell carcinomas treated with platinum-based chemotherapy. When data were stratified for the multivariate analysis, only the loss of ARID1A expression remained a significant (P=0.03) predictor of reduced progression-free survival. Of the 60 patients with ovarian clear cell carcinomas, 14 patients had measurable residual tumor after primary cytoreductive surgery. Tumors with loss of ARID1A expression were more likely to be chemoresistant than tumors with positive ARID1A expression (100.0 vs 40.0%, P=0.04). This study demonstrates that loss of ARID1A in ovarian clear cell carcinoma is a negative prognostic factor in patients treated with platinum-based chemotherapy. Measurement of ARID1A expression may be a method to predict resistance to platinum-based chemotherapy in patients with ovarian clear cell carcinoma.     

Protein expression and prognostic value of genes in the erb-b signaling pathway in advanced ovarian carcinomas

By using tissue microarrays and immunohisto-chemical analysis, we studied protein expression of genes in the erb-b signaling pathway (erb-b1; erb-b2; phosphoinositide-3-kinase, catalytic, a polypeptide [PIK3CA]; phosphatase and tensin homologue [PTEN]; phosphorylated AKT [p-AKT]; and phosphorylated extracellular signal-regulated kinase [p-ERK]) in 118 advanced ovarian carcinomas and related expression to clinicopathologic features and survival. High protein expression was seen in 15.3% of cases for erb-b2, 44.1% for erb-b1, 43.2% for PIK3CA, 51.6% for p-AKT, and 28.0% for p-ERK. Low protein levels of PTEN were seen in 41.5% of the cases and tended to be more common in well-differentiated tumors. In multivariate analysis, only high expression of both erb-b1 and erb-b2 was an independent factor in progression-free and disease-specific survival (P=.009, hazard ratio=2.46; P=.002, hazard ratio=3.023, respectively). The PI3K/AKT and RAS/MEK/ERK pathways seem to be activated in some cases of advanced ovarian carcinomas, although PIK3CA, p-AKT, p-ERK, and PTEN do not seem to be independent prognostic markers in this group of patients.     

Stromal cell-derived factor-1 (SDF-1) signalling regulates human placental trophoblast cell survival

Stromal cell-derived factor-1 (SDF-1 or CXCL12) is the physiologic ligand for the chemokine receptor CXCR4. CXCR4-mediated signalling regulates cell migration and apoptosis in certain haematopoietic and neuronal cells. Using gene profiling, we determined that CXCR4 is the only chemokine receptor for which mRNA expression is regulated during trophoblast differentiation in vitro. Based on the known effects of CXCR4 ligation, we hypothesized that CXCR4 activation may regulate placental trophoblast cell survival (i.e. protection from apoptosis), an important mechanism for the establishment and maintenance of the uteroplacental barrier. Human cytotrophoblasts (CTBs) were cultured in defined media and treated with graded doses of SDF-1 (10-100 ng/ml) or with an anti-CXCR4 neutralizing antibody. Exposure to anti-CXCR4 antibody reduced CTB cell numbers by 25-40%. Treatment with SDF-1 decreased the proportions of apoptotic terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick-end labelling(+) cells (apoptotic index [AI] of 2.79+/-0.61% [control] versus 1.88+/-0.56% [SDF-1]; P<0.05) and caspase-activated cells (AI of 7.95+/-2.49% [control] versus 3.81+/-1.49% [SDF-1]; P<0.05). We determined that SDF-1 also activated the triple MAP Kinase isoforms ERK1/2 and p38 in trophoblasts. Immunocytochemistry confirmed SDF-1-induced nuclear translocation of phosphorylated ERK1/2. Blocking of ERK1/2 signalling with the specific inhibitor PD98059 reversed SDF-1-mediated inhibition of apoptosis (AI of 1.65+/-0.34 [SDF-1] versus 3.50+/-0.5 [SDF-1 + PD98059]; P<0.05), suggesting that SDF-1 acts through this pathway as a trophoblast survival factor. These results indicate that SDF-1/CXCR4 signalling stimulates anti-apoptotic pathways in cultured trophoblasts. This chemotactic ligand/receptor system may promote trophoblast survival during pregnancy. Alterations in SDF-1 and/or CXCR4 expression or function may be associated with specific pregnancy disorders.     

Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas

Epithelial cadherin forms a complex with alpha-, beta-, and gamma-catenin proteins. Reduced expression of E-cadherin-catenins has been shown in human carcinomas and is associated with low histologic differentiation, increased risk of invasion, and metastatic disease. The immunoexpression pattern of E-cadherin and beta-catenin (reduced versus preserved phenotype) was evaluated in 104 primary ovarian carcinomas and related to clinicopathologic features of the tumors. The immunoexpression pattern of E-cadherin was associated with International Federation of Gynaecology and Obstetrics (FIGO) staging (P = 0.043), histologic subtype (P = 0.001), peritoneal metastasis (P = 0.006), and residual tumor (P = 0.036). The reduced phenotype of E-cadherin that was observed in 64% of the carcinomas (67/104) was associated with advanced stage tumors, serous carcinomas, presence of peritoneal metastasis, and residual tumor larger than 2 cm. The immunoexpression pattern of beta-catenin was associated with histologic subtype (P = 0.005), tumor differentiation (P = 0.025), and peritoneal metastasis (P = 0.041). The reduced phenotype of beta-catenin that was observed in 74% of the carcinomas (77/104) was associated with advanced stage tumors, poorly differentiated serous and clear cell carcinomas, presence of peritoneal metastasis, and residual tumor. The immunoexpression pattern of E-cadherin was correlated with beta-catenin (P = 0.001). The reduced phenotype for both E-cadherin and beta-catenin was associated with histologic subtype (P < 0.001) and peritoneal metastasis (P = 0.001). In conclusion, the immunohistochemical profile of E-cadherin and beta-catenin may be useful in identifying a particular subpopulation of ovarian cancer patients who are characterized by an adverse clinical outcome, because the reduced phenotype of these molecules was associated with poor tumor differentiation, peritoneal metastasis, and advanced FIGO stage tumors.     

Lymphocyte Subset Recovery and Outcome after Autologous Hematopoietic Stem Cell Transplantation for Plasma Cell Myeloma

Rapid immune reconstitution—particularly of natural killer cells (NK cells)—after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with protection from relapse. Whether such an association also exists after autologous stem cell transplantation is less clear. We retrospectively assessed lymphocyte subsets after autologous HSCT in 114 patients and correlated lymphocyte recovery with outcome. CD8 T cell and NK cell counts recovered rapidly to pretransplantation levels, whereas B cell and CD4 T cell recovery were delayed. Compared with patients with low NK cells (<100/uL), high NK cell count at 1 month after HSCT was associated with significantly prolonged progression-free survival: for NK cells 100 to 200/uL hazard ratio [HR], .33 (95% confidence interval [CI]; .16 to .80; P = .004); for NK cells > 200/μL HR, .27 (95% CI, .13 to .58; P = .001). No significant protective effects were associated with rapid recovery of any other lymphocyte subset. None influenced overall survival (OS) or time to next treatment. Early NK cell recovery is associated with better progression-free survival after autologous HSCT. The failure to detect an effect on OS might be due to the salvage strategies available to these patients.     

Significance of amyloid A immunoexpression in the prognosis of renal cell carcinoma

The study investigated immunoexpression of amyloid A (AA) in clear cell renal cell carcinoma (CCRCC) and evaluated its clinicopathologic correlation, particularly in disease progression. Expression of AA protein was evaluated in patients with CCRCC by immunohistochemistry. 146 cancerous tissue samples from 86 male and 60 female patients were studied. The relationship between AA protein expression and TNM stage, nuclear grade, renal capsule invasion, perirenal invasion, and survival of the patients were assessed. Thirty four percent of CCRCC cases were AA positive. The positive AA immunoexpression was related to higher Fuhrman nuclear grade, presence of perirenal invasion of the tumor, and poor survival of patients with CCRCC. There was not any statistically significant difference between patients' gender, status of capsule invasion, and stages of the tumor in terms of AA immunoexpression. Tumor stage (Hazard ratio (HR) = 7.76 (95% CI: 2.43–24.8) for stage 3 and HR = 29.9 (95% CI: 6.97–128.32) for stage 4) and AA immunoexpression (HR = 2.16 (95% CI: 1.01–4.64) were found to be associated with survival of the patients with CCRCC in Cox regression analysis. Immunoexpression of AA was increased in high grade CCRCCs. Immunoexpression of AA was associated with poor survival in patients with CCRCC. Thus, AA staining might be used as a useful immunohistological marker for the prediction of poor prognosis in renal cell cancer.     

弥漫大B细胞淋巴瘤免疫表型分型与预后的关系

目的 探讨弥漫大B细胞淋巴瘤（DLBCL）的免疫表型之生发中心B细胞样（GCB）和非GCB两个亚型的特征及其与DLBCL预后的关系。方法 根据肿瘤细胞免疫组织化学EnVision法标记CD10、bc1-6、MUM-1的表达情况,将133例DLBCL分为GCB和非GCB两个亚型。对以下指标的5年总生存率（OS）及5年无进展生存率（PFS）进行了比较：（1）CD10、bc1-6和MUM-1的阳性和阴性病例;（2）GCB亚型与非GCB亚型;（3）不同国际预后指数（IPI）分组中GCB亚型与非GCB亚型的关系。结果 133例DLBCL中,44例（33．1％）CD10阳性,48例（34．6％）bc1-6阳性,60例（45．1％）MUM-1阳性。CD10阳性DLBCL患者的5年OS及PFS均明显高于CD10阴性患者（P=0．041和0．031）;bc1-6阳性DLBCL患者的PFS明显高于bc1-6阴性患者（P=0．044）,MUM．1阳性DLBCL患者的5年0s及PFS均明显低于MUM-1阴性患者（P=0．031和0．028）。GCB型54例（40．6％）,非GCB型79例（59．4％）。GCB型5年OS及PFS均明显高于非GCB型（P=0．004和0．003）。国际预后指数（IPI）0-1分组及2-5分组中,GCB型5年OS及PFS均明显高于非GCB型（IP10-1分组P=0．019和0．014,2-5分组P=0．006和0．009）,其中IPI2-5分组中的非GCB预后最差。结论 DLBCL亚型及其与IPI联合分析可以作为预测患者预后的有效指标。     

Chemokine Receptor CXCR4 Is a Novel Marker for the Progression of Cutaneous Malignant Melanomas

The CXCR4/CXCL12 pathway has recently been reported to be involved in stimulating the metastasis of many different neoplasms, in which CXCR4 activates various phenomena such as chemotaxis, invasion, angiogenesis and proliferation. The purpose of this study was to analyze a possible association between the expression of chemokine receptors CXCR4, CCR6 and CCR7 with the clinicopathological features of cutaneous malignant melanoma, and to assess the usefulness of these chemokine receptors for diagnosis and prognosis. In our study, a percentage of immunoexpression of both CXCR4 and its ligands CXCL12 was associated with high clinical risk. In contrast, the patients with a low immunoexpression of CXCR4 and CXCL12 had low clinical risk. CCR6 and CCR7 immunoexpressions were also correlated with some clinical parameters, but seemed no more useful than CXCR4. These data suggest that the assessment of CXCR4 immunoexpression is a novel tool for predicting tumor aggressiveness in malignant melanomas, and in particular, a high immunoexpression percentage of CXCR4 and CXCL12 might be a sign of a poor prognosis.     

Expression of endothelin 2 and localized clear cell renal cell carcinoma

Despite the rising incidence of clear cell renal cell carcinoma, the molecular events that support its development and progression remain unclear. Herein, we evaluate the association of endothelin 2 expression with both clear cell renal cell carcinoma development and progression-free survival. We conducted real-time polymerase chain reaction to determine endothelin 2 expression levels on 238 patients who underwent nephrectomy for localized clear cell renal cell carcinoma, 161 of whom also had adjacent normal kidney samples available for analysis. To evaluate associations with clear cell renal cell carcinoma development, linear mixed models were used to compare differential expression between tumor and a normal kidney as well as to explore interactions with clinicopathologic features. To evaluate associations with prognosis, Cox proportional hazards models were used to assess the association of progression-free survival and endothelin 2 expression in tumor tissue. Overall, endothelin 2 expression was higher in tumor samples versus patient-matched normal kidney samples, with an average fold change of 1.99 (95% confidence interval, 1.48-2.60; P < .0001). This overexpression in tumor versus normal kidney samples was more pronounced in low- compared with high-grade tumors (interaction, P = .0002), in early- compared with late-stage tumors (interaction, P = .001), and in tumors without compared with those with necrosis (interaction, P = .001). Moreover, an increasing endothelin 2 expression in tumors was associated with a longer progression-free survival (hazard ratio, 0.89; 95% confidence interval, 0.80-0.99; P = .03); however, after controlling for known clinicopathologic factors, this association was attenuated (hazard ratio, 0.99; 95% confidence interval, 0.89-1.09; P = .7). Up-regulation of endothelin 2 is a common and early event in localized clear cell renal cell carcinoma. Higher tumor expression of endothelin 2 is associated with a longer progression-free survival but not after adjustment for well-known pathologic indices. Thus, although endothelin 2 does not appear to be an independent prognostic marker, there is evidence of a putative role in clear cell renal cell carcinoma progression. If supportive mechanistic data can be produced, endothelin 2 could represent a potential target for chemopreventive or neoadjuvant therapeutics for clear cell renal cell carcinoma.     

Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma: pattern of expression and correlation with clinical outcome

Nasopharyngeal carcinoma (NPC) is a tumor derived from epithelial cells and Epstein-Barr virus infection has been reported to be a cause of this disease. Chemokine receptor CXCR4 was found to be involved in HIV infection and was highly expressed in human malignant breast tumors and the ligand for CXCR4, CXCL12 (SDF-1), exhibited high expression in organs in which breast cancer metastases are often found. The metastatic pattern of NPC is quite similar to that of malignant breast tumors. In this study, we investigated the expression of CXCR4 in nasopharyngeal carcinoma (NPC) tissues by immunohistostaining. We found different staining patterns, which included localization in the nucleus, membrane, cytoplasm or a combination of them. The staining intensity was also variable among samples. The metastatic rates in patients with high compared to low or absent expression was 38.6% versus 19.8%, respectively (P = 0.004). High expression of CXCR4 was associated with poor overall survival (OS = 67.05% versus 82.08%, P = 0.0225). These results suggest that CXCR4 may be involved in the progression of NPC and that a high level of CXCR4 expression could be used as a prognostic factor.     

Expression patterns of SDF1/CXCR4 in human invasive breast carcinoma and adjacent normal stroma: Correlation with tumor clinicopathological parameters and patient survival

SDF-1/CXCR4 axis is involved in various steps of breast tumorigenesis such as tumor growth, angiogenesis and metastasis. The goal of the present study is to demonstrate in detail the immunohistochemical distribution of SDF-1 and CXCR4 in invasive breast carcinomas and identify possible correlation of their expression patterns with clinicopathological parameters and patients survival. We investigated the immunoexpression of CXCR4 and SDF1 in 76 invasive breast carcinomas. Both SDF-1 and CXCR4 had statistically significant higher expression in carcinomas compared with adjacent normal breast tissue. Furthermore the expression of CXCR4 in intratumoral fibroblasts had a positive correlation with overall and disease-free survival, while SDF1 membranous immunopositivity in normal breast epithelial cells was a risk factor for relapse. In addition, expression of SDF1 in fibroblasts of normal breast tissue was positively associated with tumor grade. Overall, our results suggest that the differential expression of CXCR4 in intratumoral stroma and SDF1 in adjacent normal mammary cells may predict clinical outcome in breast cancer patients.     

Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasms

To clarify possible roles of adhesion molecules including E-cadherin, beta- and gamma-catenin, CD44s, CD44v6, CD56, and CD99 in ovarian serous neoplasms, an immunohistochemical study was undertaken for 23 benign, 40 borderline, and 95 malignant ovarian serous neoplasms using tissue microarray (TMA). Significantly reduced expression of E-cadherin, and overexpression of CD44s, CD56, and CD99 were more frequently observed in adenocarcinomas than in benign and borderline tumors. Expression of CD44v6 and nuclear beta- and gamma-catenin were detected only in borderline tumors and adenocarcinomas. Reduced expression of E-cadherin was also correlated with high tumor grade (P=0.03), presence of peritoneal seeding (P=0.03), and low overall survival rate (P=0.02). Overexpression of CD44s was significantly associated with high tumor grade (P=0.04), advanced stage (P=0.03), and low overall survival rate (P=0.02). CD56 was increasingly expressed in the case of advanced stage (P=0.005) and peritoneal seeding (P=0.001). Nuclear staining for gamma-catenin was correlated with tumor progression (P=0.004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.02). Only CD44s expression and stage were correlated with overall survival in multivariate study. These results suggest that although E-cadherin, CD44s, CD56, and nuclear gamma-catenin immuno-expression seem to be useful prognostic markers for serous neoplasm of the ovary, CD44s expression and FIGO stage are independent prognostic factors.     

外科手术与内镜介入治疗可切除肺腺样囊性癌的疗效比较

目的 探讨外科手术与内镜介入两种方法治疗可切除肺腺样囊性癌的临床疗效。方法 回顾性研究。纳入天津市胸科医院2010年1月—2017年12月收治的可切除肺腺样囊性癌患者25例。其中,男18例、女7例,年龄42~87（56.6±12.5）岁。25例患者根据治疗方式不同分为2组,行内镜介入治疗的11例患者为内镜组,行外科手术治疗的14例患者为手术组。对比2组患者手术时间、术中出血量、术后住院时间,以及2组患者围手术期呼吸系统疾病、心血管系统疾病并发症发生情况;术后定期随访,比较2组患者肿瘤复发和转移情况,以及总体生存期和无复发生存期。结果 2组患者性别、年龄、体质量指数及肿瘤大小、位置、分期等基线资料比较,差异均无统计学意义（P值均>0.05）。患者均顺利完成手术,无R2切除患者。手术组患者手术时间（187.4±37.6）min、术中出血量为（107.2±31.3）mL,分别大于内镜组的（105.8±19.6）min、（45.89±14.66）mL,差异均有统计学意义（t=7.00、6.51,P值均<0.001）。手术组发生呼吸系统并发症8例、心血管系统并发症3例,内镜组发生呼吸系统并发症4例、心血管系统并发症2例,差异均无统计学意义（P值均>0.05）。25例患者术后随访6~91个月,中位随访时间62.3个月。随访期间,手术组患者死亡2例,内镜组患者死亡5例。内镜组术后胃肠部位转移1例、局部进展4例,手术组术后同侧肺转移1例、无局部复发,2组复发转移率比较,差异无统计学意义（P=0.056）。内镜组总体生存期平均为61.9 [95%可信区间（CI） 48.0~75.9]个月、无复发生存期平均为50.7 （95%CI 31.6~69.8）个月,分别短于手术组的83.1 （95%CI 75.8~90.4）个月、86.7 （95%CI 78.6~94.8）个月,仅无复发累积生存期差异有统计学意义（χ²=5.46,P=0.020）。结论 外科手术治疗可切除的肺腺样囊性癌,患者总体生存期和无复发生存期优于内镜治疗,且手术治疗的患者复发率较低,因此推荐其为可切除的肺腺样囊性癌的首选治疗方案。     

Low levels of WWOX protein immunoexpression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours

Aims:  To correlate the immunohistochemical detection of WWOX with histological measures and disease progression within the whole spectrum of urothelial bladder neoplasms.
Methods and results:  One hundred and one patients with primary bladder tumours were retrospectively analysed. Immunohistochemically, a polyclonal antibody was utilized and the level of WWOX protein expression was analysed by using a combined score system based on intensity of the reaction and percentage of immunoreactive tumour cells. WWOX protein expression was consistently expressed in non-neoplastic urothelium, whereas a progressive loss of immunoreactivity was observed as tumour grade and stage increased ( P  < 0.05). Principal component analysis showed that reduced WWOX immunoexpression was significantly associated with high histological grades ( P  = 0.001), advanced stage ( P  = 0.002), tumour size ( P  = 0.04) and cancer progression ( P  = 0.028). Invasive urothelial carcinomas of the bladder with squamous metaplasia presented the lowest levels of WWOX protein. Kaplan–Meier analyses demonstrated a significant correlation between loss of WWOX expression and a shorter progression-free survival ( P  = 0.042), whereas the prediction of overall survival achieved borderline significance ( P  = 0.053).
Conclusion:  Loss of WWOX immunoexpression strongly correlates with classical clinicopathological factors and appears to be a potential predictive marker of progressive disease.     

Significance of topoisomerase IIIβ expression in breast ductal carcinomas: strong associations with disease-specific survival and metastasis

Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase IIIβ, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase IIIβ in breast cancer and its relationships with clinicopathologic features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase IIIβ, estrogen receptor, progesterone receptor, HER-2, BRCA-1, p53, and Ki67. Immunostaining for topoisomerase IIIβ was found in 33.9% of breast carcinomas, and immunopositivity was correlated with distant metastasis (P = .036) and death (P = .006). Decreased expression of topoisomerase IIIβ correlated with low expression of Ki67 (P < .001) and negativity for HER-2 (P < .001), BRCA-1 (P = .001), and p53 (P < .001). In the multivariate analysis, topoisomerase IIIβ expression was a significant predictor of survival (hazard ratio, 3.006 [95% confidence interval, 1.582-5.715]; P = .001). In conclusion, topoisomerase IIIβ expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival.     

Different CXCR4 Expression According to Various Histologic Subtype of Papillary Thyroid Carcinoma

Functional chemokine (C-X-C motif) receptor 4 (CXCR4) is well known to be over-expressed in papillary thyroid carcinoma (PTC). The aim of this study was to evaluate whether or not the expression of CXCR4 is different by histological subtypes of PTC and to elucidate the relationship between the expression of CXCR4 and clinicopathologic factors. CXCR4 expression in 127 PTC samples was assessed using immunohistochemical staining. The expression of CXCR4 showed different patterns according to the histological subtype of PTC (p?<?0.001). A strong expression of CXCR4 was observed more frequently in the poorly differentiated region of PTC (81.0 %) than in classical PTC (50.0 %). Strong CXCR4 expression was less frequently shown in follicular variant (33.9 %) and in diffuse sclerosing variant (14.3 %) of PTC. CXCR4 expression showed a distinct pattern according to the histological subtype of PTC although not associated with other clinicopathological parameters.     

Clinicopathologic significance of CXCR4 expressions in patients with esophageal squamous cell carcinoma

AimsThis study was designed to investigate the biological function of CXCR4 in esophageal squamous cell carcinoma and to explore the underlying mechanism to provide potential targets for esophageal squamous cell carcinoma.MethodsA total of 101 patients with esophageal squamous cell carcinoma were included, and the relationship between CXCR4 and clinicopathological factors was analyzed. Laser scanning confocal microscopy was used to observe numbers of autophagosomes in TE-1 cell line and the ability of proliferation and invasion were evaluated meanwhile.ResultsCXCR4 is overexpressed in ESCC specimens and is associated with poor differentiation and lymphocyte metastasis. In the survival analysis, CXCR4 predicted a poor overall survival prognosis. The number of autophagosomes in the siR-CXCR4 group was decreased compared with negative group (P < 0.05), while was increased in the pcDNA3.1-CXCR4 group (P < 0.05).Western blot result show upregulation of LC3II, the ratio of LC3II/LC3I and Beclin1 in pcDNA3.1-CXCR4 group and decreased expression of LC3II, the ratio of LC3II/LC3I and Beclin1 in siR-CXCR4 group. Transwell assay show CXCR4 overexpression promote the invasion of TE-1 cells and was attenuated by autophagy inhibitor 3-Methyladenine.On the contrary, invasion cell numbers decreased in siR-CXCR4 group and was rescued by autophagy inducer Rapamycin.ConclusionCXCR4 is an indicator of poor prognosis for ESCC. CXCR4 promote autophagy and regulate cell invasion through autophagy in ESCC. Our study provides new insights for the treatment of esophageal squamous cell carcinoma and CXCR4 may serve as a therapeutic target for ESCC.     

结直肠癌原发灶中CXCR6的表达与临床意义

目的: 明确趋化因子受体CXCR6在结直肠癌原发灶中的表达特点及临床意义。方法: 收集2004年8月至2008年12月中山大学附属第一医院手术切除的143例结直肠癌标本及29例癌旁组织,应用免疫组化方法检测CXCR6的表达,采用Image-Pro Plus 6.0 软件分析图片的平均累积吸光度(mIA),分析CXCR6与同时性肝转移及预后的关系。结果: CXCR6在结直肠癌组织中呈不同程度的阳性表达,在癌旁正常组织中弱表达或不表达。结直肠癌原发灶中CXCR6的mIA在0.41~2.84之间,平均为1.54±0.04,其中同时性肝转移病例为1.63±0.05,无肝转移病例为1.41±0.08,两组比较差异有统计学意义(P<0.05)。以mIA值1.54为界,将病例划分为CXCR6低表达组(mIA<1.54)和CXCR6高表达组(mIA≥1.54)。CXCR6高表达患者的总生存率显著较低表达组差,两组差异有统计学意义(P<0.05)。多因素Cox回归分析发现年龄(P<0.05)、淋巴结转移(P<0.05)和同时性肝转移(P<0.01)为结直肠癌患者预后的独立危险因素,CXCR6为非独立危险因素。CXCR6表达与IV期肝转移患者预后无关(P>0.05),与I~III期结直肠癌患者预后呈负相关(P<0.01)。结论: CXCR6与结直肠癌肝转移的发生相关,它有望成为结直肠癌肝转移治疗的一个重要靶点。