Expression of chemokine receptor CCR7 is associated with cervical lymph node metastasis of oral squamous cell carcinoma

Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. The present study was designed to examine the expression of chemokine receptor CCR7 in oral squamous cell carcinoma (OSCC), and to investigate the possible role of CCR7/CCL21 interaction in neck lymph node metastasis of OSCC. By using immunohistochemistry, RT-PCR and Western Blot, expression of CCR7 was examined in 85 cases of oral squamous cell carcinoma, and Tca8113 and ACC cell lines. CCL21-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber. In vitro adhesion assay was shown for banding of tumor cell lines to submandibular lymph nodes with or without anti-CCR7 antibody treatment. Immunohistochemical staining showed 65.9% (56/85) of positive CCR7 expression in OSCC tissues. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P=0.015) and was also associated with tumor size (P=0.014), and clinical stage (P=0.009). RT-PCR and Western Blot also confirmed positive CCR7 expression in oral squamous cell carcinoma and Tca8113 cell line, and negative CCR7 expression in normal oral mucosa and ACC cell line. CCL21 stimulation increased the ability of CCR7-positive Tca8113 cells passing through the Matrigel membrane. CCR7-positive Tca8113 cells also showed stronger adhesion to lymph nodes, which could be partly blocked by anti-CCR7 antibody incubation. These results indicated that the chemotactic CCR7/CCL21 interaction may be a possible mechanism for induction of directional lymph node metastasis by oral squamous cell carcinoma.     

Expression of chemokine receptors in human gastric cancer.

The roles of chemokine receptors in cancer metastatic processes continue to draw research attention. Here we evaluated the expression profiles of the chemokine receptors CCR7 and CXCR4 in gastric cancer, and their potential use as prognostic markers. The expressions of CCR7 and CXCR4 mRNA were analyzed by RT-PCR in 10 human gastric cancer cell lines and in 43 gastric cancer tissues, and in an additional 307 gastric cancer tissues by immunohistochemistry. Clinicopathological features and the prognoses of patients were also evaluated versus the expression of these two cytokine receptors. CCR7 and CXCR4 mRNA were found to be expressed in all gastric cancer cell lines, whereas their mRNA expression rates in gastric cancer tissues were 83.7% (36/43) and 100% (43/43), respectively. Immunohistochemical staining of the 307 gastric cancer tissues showed that the expression rates of CCR7 and CXCR4 were 22.5% (69/307) and 36.5% (112/307), respectively. Multivariate analysis of the immunohistochemistry results showed that the expression rate of CCR7 was significantly higher in differentiated than in undifferentiated gastric cancertypes (35.1 vs. 15.3%, p<0.001), and that CXCR4 was expressed at a higher rate in intestinal cancer than in diffuse-type cancer (58.8 vs. 22.3%, p<0.001). However, in contrast to previous studies, the expressions of CCR7 or CXCR4 were not associated with lymph node metastasis. Moreover, the prognosis of patients with CCR7-positive tumors was better than that of patients with CCR7-negative tumors, but no such correlation was observed for CXCR4 expression. In conclusion, the expressions of the chemokine receptors CCR7 and CXCR4 were found to be high in differentiated and intestinal-type gastric cancers, respectively.     

趋化因子受体CCR7与PI3K/Akt通路在胃癌组织中的表达及意义

目的 观察趋化因子受体CCR7和磷脂酰肌醇-3-激酶（PI3K）、蛋白激酶B（PKB或Akt）在胃癌组织中的表达情况,探讨CCR7与PI3K/Akt通路的关系。方法 采用RT-PCR法检测32例胃癌及相应癌旁对照组织中CCR7mRNA、PI3KmRNA、AktmRNA的表达;Western Blotting法检测CCR7、p-Akt蛋白的表达。结果 胃癌组织中CCR7mRNA、PI3KmRNA、AktmRNA与癌旁对照组织的表达水平相比,差异均有显著性（P〈0.001）,且CCR7mRNA与PI3KmRNA、AktmRNA表达呈正相关（P〈0.05）。CCR7、P-Akt蛋白在胃癌组织中的表达水平明显高于癌旁对照组织（P〈0.05）,两者表达与肿瘤TNM分期、浸润深度、分化程度、淋巴结转移与远处转移有关（P〈0.05）,并且CCR7、P-Akt表达水平呈正相关（P〈0.05）。结论 胃癌组织中高表达的CCR7可能通过PI3K/Akt通路促进胃癌的侵袭转移。     

血管内皮生长因子-C与CCR7在大肠癌中的表达

目的　探讨血管内皮生长因子 C和CCR7在大肠癌中的表达及其与淋巴结转移的关系。方法　采用原位杂交和双重免疫组织化学技术,以41例大肠癌和41例癌旁正常大肠黏膜为研究对象,检测VEGF -CmRNA和CCR- 7mRNA的表达情况和微淋巴管密度(LVD )。结果　VEGF CmRNA和CCR -7mRNA在大肠癌组织中阳性表达率分别为3 4.15 % (14 / 41) ,5 8.5 4%(2 4/ 41)。VEGF CmRNA、CCR7mRNA和LVD均与大肠癌淋巴结转移密切相关(P <0 .0 5 )。结论　VEGF CmRNA、CCR7mRNA和LVD与大肠癌的淋巴结转移密切相关,联合检测其在内镜活检组织中的表达有助于预测淋巴结转移的发生。     

CD168在胃癌组织中的表达及预后意义

目的 探讨胃癌组织中透明质酸介导的细胞游走受体(CD168)的表达情况与各临床病理因素及其预后的关系,评估其在胃癌侵袭转移过程中的作用及预测胃癌患者预后的价值.方法 采用免疫组织化学法检测72例胃癌组织和26例正常胃黏膜组织中CD168的表达情况.同时评估CD168的表达与临床病理因素(年龄、性别、组织学、肿瘤浸润深度、淋巴结转移和临床分期)之间的关系.用Kaplan-Meier法评估胃癌患者术后5年生存率.结果 胃癌组织中CD168阳性表达率为58.3％,与正常胃黏膜中的阳性表达率(19.2％)比较,差异有统计学意义(P=0.001);CD168阳性表达率与肿瘤分化程度(P=0.001)、淋巴结转移(P=0.003)、临床分期等(P=0.020)有显著相关性.CD168阳性表达率与年龄、性别、肿瘤大小和肿瘤浸润深度无显著相关性.胃癌患者的生存期分析显示,CD168阴性组5年生存率(67.2％)显著高于CD168阳性组5年生存率(29.8％),两组间差异有统计学意义(P=0.01).结论 CD168高表达与胃癌的浸润和转移密切相关,可以作为预测胃癌预后的一个生物学指标.     

Association between the expression of chemokine receptors CCR7 and CXCR3, and lymph node metastatic potential in lung adenocarcinoma

Chemokines and their receptors are essential for leukocyte trafficking, and are also involved in cancer metastasis to specific organs. Although the migration of tumor cells into the lymph nodes is an important aspect of cancer, the processes involved are poorly understood. Chemokine receptors CCR7 and CXCR3 have been shown to play an important role in tumor cell migration and lymph node metastasis. Therefore, the assessment of chemokine receptor expression on lung adenocarcinomas may improve the prediction of the spread of this carcinoma to the lymph nodes. In this study, we examined the expression and function of these two chemokine receptors (CCR7 and CXCR3) in lung adenocarcinoma. By using flow cytometry, they were detected in all of the lung adenocarcinoma cell lines examined. In the chemotaxis assays, A549 cells exhibited CCL21-induced migration, which was significantly suppressed by neutralizing anti-CCR7 antibody. The CXCL10-induced migration of A549 cells was also significantly suppressed by neutralizing anti-CXCR3 antibody. In clinical lung adenocarcinoma samples, we found the expression of CCR7 and CXCR3 in 65 and 90% cases, respectively, most of which had lymph node metastasis. Importantly, the expression of CCR7 was significantly associated with lymph node metastasis, although the expression of CXCR3 was not. These results suggest that the activation of CCR7 and CXCR3 with their ligands preferentially stimulates lung adenocarcinoma metastasis to the draining lymph nodes.     

Prognostic Significance of Matrix Metalloproteinase-7 (MMP-7) Expression at the Invasive Front in Gastric Carcinoma

To evaluate the clinicopathological significance of matrix metalloproteinase-7 (MMP-7) expression in gastric carcinoma, we investigated immunohistochemically MMP-7 expression in 214 gastric carcinomas, and examined its relations with the clinicopathologic parameters including patient prognosis. MMP-7 expressed predominantly in cancer cells, and MMP-7-positive tumor cells were preferentially found in deeply invading nests, especially at the invasive front. The mean MMP-7 labeling index (LI) at the invasive front was significantly higher in tumors invading or penetrating the muscularis propria and in stages II-IV than within the submucosal layer and in stage I, respectively ( P <0.001). Statistical analysis revealed that MMP-7 LI at the invasive front was related to lymph node metastasis, vascular invasion, and lymphatic permeation, when all 214 cases were examined as one group ( P <0.05 for all), and the cases with high MMP-7 expression at the invasive front showed significantly more unfavorable prognosis as compared with that of low MMP-7 expression tumors ( P <0.01). Multivariate analysis revealed that TNM stage and MMP-7 expression status at the invasive front were independent prognostic factors ( P =0.0017, relative risk (RR)=3.12; P =0.0019, RR=2.67, respectively). Our findings indicated that expression of MMP-7 at the invasive front is closely associated with local invasiveness, and might be a reliable prognostic marker for patients with gastric carcinoma.     

CD10-positive stromal cells in gastric carcinoma: correlation with invasion and metastasis

BACKGROUND: CD10 is a cell surface metalloproteinase expressed by a variety of normal cell types, including lymphoid precursor cells, germinal center B lymphocytes and some epithelial cells. Although accumulating data indicate that CD10 expression by stromal cells is involved in colorectal carcinogenesis and it is a novel prognostic factor in breast carcinoma, CD10-positive stromal cells and their correlation with invasion and metastasis have not been studied in gastric carcinoma. The aim of this study was to immunohistochemically investigate the rate of CD10 production in the stromal cells in our gastric carcinoma collection and clarify its correlation with invasion and metastasis. METHODS: One hundred and sixteen cases of gastric carcinoma were analyzed immunohistochemically using a monoclonal CD10 antibody (clone 56C6). RESULTS: The expression of CD10 by stromal cells was significantly higher in the primary gastric carcinomas than in normal and dysplasia mucosas (P = 0.014). More frequent expression of CD10 by stromal cells was detected in differentiated carcinoma than in undifferentiated carcinoma (P < 0.001). CD10 expression by the stromal cells was associated with depth of invasion and lymph node metastasis (P < 0.05). Stromal CD10 expression was lower in gastric carcinoma without vessel invasion than in those with vessel invasion (P = 0.001). However, no association was observed between stromal CD10 expression and TNM stage. In differentiated carcinoma, stromal CD10 expression was associated with the depth of invasion, lymph node metastasis, vessel invasion and TNM stage (P < 0.01). CONCLUSION: These results indicate that stromal cells expressing CD10 may play an important role in gastric carcinogenesis. CD10 expression by stromal cells seems to promote invasion and metastasis of differentiated gastric carcinoma.     

CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer.

PURPOSE: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer metastasis. We therefore studied the differential expression of CCR7 and CXCR4, along with that of the biomarker HER2-neu, to evaluate whether these biomarkers could predict axillary lymph node metastasis in breast cancer. EXPERIMENTAL DESIGN: Biomarker expression levels were evaluated using paraffin-embedded tissue sections of lymph node-negative (n = 99) and lymph node-positive (n = 98) T1 breast cancer by immunohistochemical staining. RESULTS: Lymph node-positive tumors showed higher rates of high cytoplasmic CCR7 staining (21.5% versus 8.5%, P = 0.013) and HER2-neu overexpression (21.5% versus 9.3%, P = 0.019) than did lymph node-negative tumors. Similarly, high cytoplasmic CXCR4 expression occurred more commonly in lymph node-positive tumors (11.2% versus 5.1%, P = 0.113). In contrast, predominantly nuclear CXCR4 staining was more likely to be found in lymph node-negative tumors (54.5% versus 37.8%, P = 0.018). Furthermore, cytoplasmic CXCR4 coexpressed with HER2-neu was the only factor associated with involvement of four or more lymph nodes (16.7% versus 1.2%, P = 0.04) among lymph node-positive tumors. When all three biomarkers (CCR7, CXCR4, HER2-neu) were utilized together, 50.0% of lymph node-positive tumors highly expressed one of these biomarkers compared with 18.8% of the lymph node-negative tumors (P < 0.0001). CONCLUSIONS: Our results suggest that the chemokine receptor CCR7 is a novel biomarker that can predict lymph node metastases in breast cancer. Utilization of additional markers, such as CXCR4 and HER2-neu, further improves the prediction of the presence and extent of lymph node involvement.     

Prognostic significance of matrix metalloproteinase-7 (MMP-7) expression at the invasive front in gastric carcinoma.

To evaluate the clinicopathological significance of matrix metalloproteinase-7 (MMP-7) expression in gastric carcinoma, we investigated immunohistochemically MMP-7 expression in 214 gastric carcinomas, and examined its relations with the clinicopathologic parameters including patient prognosis. MMP-7 expressed predominantly in cancer cells, and MMP-7-positive tumor cells were preferentially found in deeply invading nests, especially at the invasive front. The mean MMP-7 labeling index (LI) at the invasive front was significantly higher in tumors invading or penetrating the muscularis propria and in stages II - IV than within the submucosal layer and in stage I, respectively (P < 0.001). Statistical analysis revealed that MMP-7 LI at the invasive front was related to lymph node metastasis, vascular invasion, and lymphatic permeation, when all 214 cases were examined as one group (P < 0.05 for all), and the cases with high MMP-7 expression at the invasive front showed significantly more unfavorable prognosis as compared with that of low MMP-7 expression tumors (P < 0.01). Multivariate analysis revealed that TNM stage and MMP-7 expression status at the invasive front were independent prognostic factors (P = 0.0017, relative risk (RR) = 3.12; P = 0.0019, RR = 2.67, respectively). Our findings indicated that expression of MMP-7 at the invasive front is closely associated with local invasiveness, and might be a reliable prognostic marker for patients with gastric carcinoma.     

Expression of stromal cell-derived factor-1α is an independent risk factor for lymph node metastasis in early gastric cancer

Lymph node metastasis is considered to be a significant prognostic factor for early gastric cancer (EGC). However, no real consensus exists on which patient and/or tumor characteristics are associated with lymph node metastasis. We investigated whether stromal cell-derived factor (SDF)-1α expression correlates with lymph node metastasis in patients with EGC by immunohistochemically examining the expression of SDF-1α in 138 archival tissue specimens of EGC. Of these specimens, 59 (42.8%) and 79 (57.2%) were grouped into SDF-1α-positive and SDF-1α-negative groups, respectively. No significant differences existed with respect to age, gender, tumor location, proportion of tumors >20 mm in size, macroscopic type, depth of invasion or histology between the SDF-1α-positive and -negative groups. However, the SDF-1α-positive group was significantly correlated with lymphovascular invasion and lymph node metastasis. Results of the univariate analyses indicated that lymphovascular invasion, undifferentiated histology and SDF-1α positivity were statistically significant risk factors affecting lymph node metastasis in patients with EGC. Multivariate analyses showed that lymphovascular invasion [hazard ratio (HR), 8.595; 95% confidence interval (CI), 1.694-43.595; P=0.009], undifferentiated histology (HR, 2.965; 95% CI, 1.037-8.471; P=0.043) and SDF-1α positivity (HR, 2.108; 95% CI, 1.316-10.135; P=0.013) were independent risk factors predicting lymph node metastasis in EGC. In conclusion, these results suggest that SDF-1α expression in tumor cells is a predictive marker of lymph node metastasis in EGC.     

甲状腺癌中CCR7和D2-40的表达及其与淋巴结转移的关系

Objective To investigate the relationship between expression of CCR7, D2-40 and lymphnode metastasis in thyroid carcinoma tissues. Methods The expression of CCR7 and D2-40 weremeasured in 87 cases of thyroid carcinoma tissues and 20 cases of normal thyroid tissues by MAX Visionimmunohistochemical staining technique. The expression of lymphatic endothelial markers D2-40 wasapplied to calculate lymphatic microvessel density(MLVD). Results CCR7 positive rate was 66.7% in the87 cases of thyroid carcinoma tissues and CCR7 positive rate was 15% in the 20 cases of normal thyroidtissues; CCR7 positive rates were counted up to 75.0%, 70.0%, 73.0% and 25.0% in PTC, MTC, FTC andUTC, retrospectively; CCR7 positive rate was 81.6%（40⁄49）in lymph node metastasis positive patients and47.4% (18⁄38) in lymph node metastasis negative patients(P<0.05). MLVD counts in thyroid carcinoma tissuesand normal tissues were (5.72±2.89) and (2.60±1.14); MLVD counts in PTC, MTC, FTC and UTC were(7.55±2.29), (6.60±1.75), (4.27±1.10) and (1.00±0.34), respectively; MLVD counts in lymph node metastasispositive patients was obviously higher than that in lymph node metastasis negative patients [(9.39±4.24), (3.24±1.67), P<0.05]. MLVD expression was positively correlated with CCR7 expression ( r_s=0.645,P<0.001).CCR7 and MLVD were positively related with lymphatic metastasis. The positive rates of CCR7 and MLVDin lymph node-positive group were higher than those in lymph node-negative group. Conclusion D2-40staining only presents in lymphatic endothelial cells. The united detection of CCR7 along with D2-40 isexpected to be the inchoate and more effective signal to judgment lymph node metastases.     

Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival

BACKGROUND: Malignant cells show increased glucose uptake in vitro and in vivo, which is believed to be facilitated by glucose transporters (Gluts). Expression of Glut1, one of the Gluts, has been described in malignancies of the esophagus, colon, pancreas, lung, and brain, but to the authors' knowledge the significance of Glut1 expression in human gastric carcinoma has not been elucidated. The objective of the current study was to examine the expression and distribution of Glut1 and its relation to clinicopathologic parameters in patients with gastric carcinoma. METHODS: Immunohistochemistry with anti-Glut1 antibody was performed on 617 gastric carcinomas and 50 tubular adenomas of the stomach. Glut1-positive and Glut1-negative carcinomas were analyzed for their clinicopathologic characteristics including histologic subtype, depth of invasion, vascular permeation, lymph node and hepatic metastasis, peritoneal dissemination, and prognosis. RESULTS: None of the adenomas expressed Glut1, whereas 182 of 617 carcinomas (29.5%) were positive for the protein. Signet ring cell carcinoma and mucinous adenocarcinoma rarely were positive (2.0% and 6.3%, respectively) and papillary adenocarcinoma (44%) showed slightly higher positivity for Glut1 than tubular (32%) or poorly differentiated adenocarcinoma (28%). Glut1-positive tumor cells were localized mainly in the central part of tumor nests with or without peripheral distribution (92%) but peripheral distribution alone was very limited (8%) (P = 0.0001). Glut1 positivity was associated with depth of invasion (P = 0.0001), lymphatic permeation (P = 0.0001), venous invasion (P = 0.0001), lymph node metastasis (P = 0.0001), hepatic metastasis (P = 0.0001), and carcinoma stage (P = 0.0001). However, peritoneal dissemination was not found to be associated with Glut1 positivity (P = 0.0833). The survival of patients who had tumors that expressed Glut1 was significantly shorter than that of patients with Glut1-negative tumors (P = 0.0001). CONCLUSIONS: In human gastric carcinoma, Glut1 is expressed late in carcinogesis and increases with disease progression. Glut1 expression is associated with tumor aggressiveness and patient survival.     

EXPRESSION OF CDX2 IS ASSOCIATED WITH CLINICOPATHOLOGIC FEATURES AND PROGNOSIS OF GASTRIC CARCINOMA.

Objective： To explore the correlation between the Cdx2 expression and clinicopathologic features of patients with gastric carcinoma, and to evaluate the role of Cdx2 as a prognostic indicator of gastric carcinoma. Methods： The expression of Cdx2 was studied using immunohistochemistry of paraffin-embedded tumor specimens from 154 patients who underwent D2 resection for gastric adenocarcinoma from 1994 to 1998. Results： Cdx2 expression was detected in 35.1% （54 of 154） of gastric carcinoma cases. Expression of Cdx2 was significantly higher in intestinal-type carcinomas than in diffuse-type carcinomas, and in cases with TNM stage Ⅰ and Ⅱ than those with TNM stage Ⅲ and Ⅳ （P〈0.001 and P=-0.012, respectively）. There was a clear negative correlation between Cdx2 expression and lymph node metastasis （P=-0.049）. The patients with Cdx2-positive expression showed higher survival rate than those with Cdx2-negative expression （P〈0.0001）. Multivariate analysis revealed that the expression of Cdx2 was the independent prognostic indicator in this series （P〈0.001）. Conclusion： These data suggest that Cdx2 has significant value in predicting prognosis of gastric carcinoma.     

Correlation effect of EGFR and CXCR4 and CCR7 chemokine receptors in predicting breast cancer metastasis and prognosis

Background

The chemokine receptors CXCR4 and CCR7 play an important role in cancer invasion and metastasis. This study investigated the expression of CXCR4, CCR7, CXCL12, CCL21, and EGFR to illustrate the role of these biomarkers in breast cancer metastasis and prognosis.

Methods

The CXCR4, CCR7, CXCL12, CCL21, and EGFR biomarkers were analyzed along with ER, PR, and HER-2/neu in breast cancer tissue microarray (TMA) specimens, including 200 primary breast cancer specimens by immunohistochemistry. Corresponding lymph nodes from the same patients were also examined using the same method.

Results

Together with their CXCL12 and CCL21 ligands, CXCR4 and CCR7 were significantly highly expressed in tumor cells with lymph node (LN) metastasis. Similarly, EGFR was expressed highly in tumors with LN metastasis. The ligands were especially expressed in metastatic tumors than in primary tumors from the same patients. Moreover, the expression of both CXCR4 accompanied by CCR7 and CXCL12 accompanied by CCL21 were up-regulated. Kaplan-Meier survival analysis revealed that patients exhibiting high CXCR4, CCR7, and EGFR expression experienced a shorter survival period compared with those with low expression.

Conclusions

The expression of CXCR4, CCR7, and EGFR may be associated with LN metastasis. Moreover, the expression of these receptors can serve as an indicator of undesirable prognosis in patients with breast cancer.     

Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: a pathway to metastatic progression in human breast cancer

We have examined whether the extended life span of cells induced by Bcl-2 in T(1) ductal breast carcinomas might favor the acquisition and accumulation of genetic alterations that induce lymph node metastases. We analyzed the expression of c-Myc, c-erbB-2 and epidermal growth factor receptor by immuno-histochemistry in a group of 142 T(1) (<2 cm) ductal breast carcinomas embedded in paraffin, previously studied for p53 mutation and Bcl-2 over-expression. We also measured the apoptotic status and estimated the excess risk (pOR) for lymph node metastasis according to the number of accumulated oncogene alterations and Bcl-2 and p53 expression. The linear relationship between number of oncogene alterations and presence of lymph node metastasis was statistically significant in Bcl-2-positive tumors (trend test, p = 0.03), p53-mutated tumors (trend test, p = 0.08) and tumors with loss of apoptosis (trend test, p = 0.08). Very large associations (pOR > 12) between the number of oncogene alterations and lymph node metastasis were observed among Bcl-2-positive tumors that showed increased loss of apoptosis (trend test, p = 0.03). Furthermore, in p53-negative tumors, a strong linear association was found between the number of oncogene alterations and risk of lymph node metastasis among Bcl-2-positive tumors (trend test, p = 0.03). In human T(1) ductal breast carcinoma, over-expression of Bcl-2 along with loss of apoptosis might render breast cancer cells susceptible to the acquisition of additional genetic lesions related to disease progression among p53-negative tumors. Thus, in breast cancer, there are at least 2 pathways to progression: Bcl-2- and p53-dependent mechanisms.     

Further evidence that altered p16/CDKN2 gene expression is associated with lymph node metastasis in squamous cell carcinoma of the esophagus

Esophageal squamous cell carcinoma (ESCC) has high malignant potential with a poor outcome. Lymph node metastasis is the most useful indicator for predicting the outcome of ESCC. The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate CDK4-mediated phosphorylation of RB protein in the cell cycle. We immunohistochemically detected p16, cyclin D1, and RB expressions in both primary lesions and metastatic lymph nodes in ESCC. Among the 50 ESCC primary lesions, 24 (48%) were positive for p16, while 26 (52%) were negative for p16. Sixteen (32%) were p16-positive, 34 (68%) were p16-negative among the 50 ESCC metastatic lymph nodes. Eight cases (16%) were p16-positive in primary lesion and p16-negative in lymph node, however, no cases that was p16-negative in the primary tumor exhibited p16-positivity in metastatic lymph nodes (p < 0.0001). Seventeen (34%) of the 50 ESCC primary lesions were cyclin D1-positive, while 33 (66%) were cyclin D1-negative. Twenty-four (48%) were cyclin D1-positive, 26 (52%) were cyclin D1-negative among the 50 metastatic lymph nodes. Five cases (10%) were cyclin D1-positive in primary lesion and cyclin D1-negative in lymph node, and 12 cases (24%) were cyclin D1-negative in primary lesion and cyclin D1-positive in lymph nodes. Nine cases (18%) were RB-negative in 50 primary lesions, and the rate of loss of RB expression in metastatic lymph nodes was not markedly higher than in primary lesions. Thirty-nine (78%) of 50 primary lesions and 46 (92%) of 50 metastatic lymph nodes had altered expression of at least one of the three G1 control genes. Tumor cell with disruption of these cell cycle regulators can get a growth advantage and metastatic potential during tumor progression, especially p16/CDKN2 alterations may be associated with lymph node metastasis in ESCC. These results also suggest that tumor cells in metastatic lymph nodes may have more aggressive proliferation and higher malignant potential than tumor cells in primary lesions.     

Decrease in ICAM-1 expression on gastric cancer cells is correlated with lymph node metastasis

Background. Lymph node metastasis is a frequent type of metastasis in patients with gastric cancer. The mechanisms responsible for this type of metastasis, however, are not clearly understood. We hypothesize that the immunosurveillance system between cancer cells and lymphocytes may be associated with the lymph node metastatic process. In this study, we examined the correlation between lymph node metastasis and intercellular adhesion molecule-1 (ICAM-1), which mediates the immunosurveillance system between tumor cells and cytotoxic lymphocytes, in gastric cancer. Methods. One hundred and forty-three specimens resected from patients with gastric cancer were investigated by staining with a monoclonal antibody against ICAM-1. We studied the correlation between the expression of ICAM-1 and various clinicopathologic factors, as well as infiltration of tumor-infiltrating lymphocytes (TILs). Results. ICAM-1 expression on gastric cancer cells was significantly decreased in patients with lymph node metastasis. The infiltration of TILs was associated with ICAM-1 expression level. The prognosis of patients with ICAM-1-negative tumors was poorer than the prognosis of those with ICAM-1-positive tumors. Conclusions. These findings suggest that ICAM-1 expression on cancer cells is closely associated with lymph node metastasis in gastric cancer, under the influence of the host immunosurveillance system. Received on Aug. 20, 1999; accepted on Jan. 5, 2000     

Expression of CK5/6 in patients with triple negative breast cancer and its clinical significance北大核心CSCD

Objective: To investigate the expression of cytokeratin 5/6 (CK5/6) in triple-negative breast cancer (TNBC) tissues and its clinical significance. Methods: A total of 347 invasive TNBC patients with complete follow-up accepted operation and confirmed by pathology and immunohistochemistry were collected from January 2010 to December 2012 in Yueyang Hospital of Integrated Traditional Chinese & Western Medicine and Huangpu District Central Hospital. The relationship between CK5/6 expression and clinicopathological features and the effect of CK5/6 on prognosis of TNBC patients were retrospectively analyzed. Results: Of 347 TNBC patients, the expression of CK5/6 was positive in 221 cases (63.8%, 221/347). The expression of CK5/6 was positively correlated with lymph node metastasis (P = 0.027, r = 0.127) and Ki-67 expression (P < 0.001, r = 0.208). The tumor size, clinical stage, lymph node metastasis and CK5/6 were independent prognostic factors of the disease-free survival (DFS) or overall survival (OS) in TNBC patients (all P < 0.05). After the median follow-up of 63 months, the recurrence and metastasis occurred in 21 cases with CK5/6 negative expression, and the death occurred in 15 cases of CK5/6-negative group; while 62 cases of recurrence and metastasis and 52 cases of death were in CK5/6-positive group. The median DFS and OS of TNBC patients in CK5/6-negative group were longer than those in CK5/6-positive group (P = 0.015, P = 0.007). Chemotherapy of anthracycline combined with paclitaxel was beneficial for DFS and OS of TNBC patients in CK5/6-positive group (both P < 0.05), while there was no benefit in CK5/6-negative group (both P > 0.05). Conclusion: The positive expression of CK5/6 is an important risk factor for the prognosis of TNBC patients. The CK5/6-positive patients achieves more benefits in chemotherapy of anthracycline combined with paclitaxel as compared with the CK5/6-negative patients. © 2019 by TUMOR.