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.     

Cyclin D1 expression in breast cancer patients receiving adjuvant tamoxifen-based therapy.

PURPOSE: The objective of our study was to determine the clinical relevance of cyclin D1 expression in hormone receptor-positive breast cancer patients who were treated with tamoxifen-based therapy. EXPERIMENTAL DESIGN: We assessed expression of cyclin D1 in surgical specimens of breast carcinoma by means of immunohistochemistry. Patients had been enrolled in either Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathologic factors. RESULTS: Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin D1 was associated with poor outcome in both cohorts. Overall survival was significantly shorter in patients with cyclin D1-positive tumors compared with patients with cyclin D1-negative tumors [adjusted hazard ratio (HR) for death (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03; adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P < 0.0001]. Relapse-free survival was also shorter in patients with cyclin D1-positive tumors than in patients with cyclin D1-negative tumors [adjusted HR for relapse (ABCSG Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005]. CONCLUSION: Cyclin D1 expression is an independent poor prognostic factor in women with early-stage, hormone receptor-positive breast cancer who received adjuvant tamoxifen-based therapy.     

细胞周期蛋白D1、CDK4在乳腺癌中的表达及其临床意义

目的：研究乳腺癌组织周期蛋白D1、CDK4的蛋白表达定位、表达水平,及与P21蛋白表达、与临床病理指标的关系及其预后意义。方法：①应用免疫组织化学染色方法,检测106例乳腺癌组织石蜡切片上的周期蛋白D1、CDK4的蛋白定位和蛋白表达,比较其与P21的蛋白表达,与临床病理学指标,如病理类型、组织学分型、组织学分级、淋巴结状态、雌激素受体状态、TNM分期等之间的关系;②对周期蛋白D1、CDK4、P21及临床病理指标如肿瘤的组织学分级、淋巴结状态、TNM分期、ER状态等,应用Kaplan-Meier法Log-rank检验进行单因素生存分析,应用Cox比例风险模型进行多因素生存分析。结果：①周期蛋白D1表达定位于细胞核、CDK4的表达位于细胞质和细胞核,周期蛋白D1的阳性率为30.2%,CDK4的阳性率为53.8%。②周期蛋白D1及CDK4的表达与乳腺癌的病理诊断组织学分型、组织学分级、ER状态、临床TNM分期、淋巴结状态、P21蛋白表达水平无关（P＞0.05)。周期蛋白D1的蛋白表达与DCK4的蛋白表达相关（P＜0.05)。③单因素分析提示影响140个月无瘤生存率及总生存率的因素有：临床TNM分期、组织学分级、腋淋巴结状态、周期蛋白D1的蛋白表达（P＜0.05)。在无腋淋巴结转移亚组周期蛋白D1蛋白表达单因素生存分析无统计学意义（P＞0.05),在腋淋巴结有转移亚组周期蛋白D1是影响140个月无瘤生存率和总生存率的因素（P＜0.01)。④多因素生存分析结果表明周期蛋白D1、P21蛋白表达、组织学分级是影响乳腺癌患者无瘤生存率和总生存率的独立预后因素（P＜0.05)。结论：周期蛋白D1、P21的蛋白表达水平及组织学分级可能是判断乳腺癌术后生存的有效指标,综合应用这些指标可能更有帮助。     

Cyclin D1 overexpression related to retinoblastoma protein expression as a prognostic marker in human oesophageal squamous cell carcinoma.

The relationship between aberrant expression of cyclin D1 and retinoblastoma (RB) protein and clinicopathological factors was investigated in 80 patients with oesophageal SCC using immunohistochemical analyses. Heterogeneous staining of cancer cell nuclei with antibody to cyclin D1 was found in 31.3% of patients (25 out of 80 patients). Nuclear staining of cancer cells with anti-RB antibody was homogeneous in 10.0% (8 out of 80 patients) and heterogeneous in 58.8% (47 out of 80 patients). Among cases with homogeneous staining for RB protein, 75% (six out of eight patients) exhibited simultaneous positivity for cyclin D1 (P < 0.05). No significant relationship was found between cyclin D1 or RB protein expression and various clinicopathological parameters. The prognosis of patients with cyclin D1-positive tumours was significantly poorer than that of the other patients (P < 0.01). In addition, when patients with cyclin D1-positive and -negative tumours were stratified according to presence or absence of lymph node metastasis and RB status, the cumulative survival rates in the cyclin D1-positive groups were significantly lower for patients without lymph node metastasis (P < 0.01) and for patients whose tumours were positive for RB (P< 0.0001). These findings suggest the possibility that cyclin D1 positivity is a useful prognostic marker related to lymph node metastasis and RB protein expression in human oesophageal SCC, in addition to clinicopathological factors.     

２９３例乳腺癌患者术后预后因素分析

目的：探讨２９３例乳腺癌患者月经情况、术后Ｔ分期、Ｎ分期、受体、术后放疗、化疗及内分泌治疗等因素对患者无病生存时间及总生存时间的影响。方法：收集我院２００２～２００６年２９３例乳腺癌患者术后的完整随访资料,选择可能对乳腺癌术后患者预后产生影响的非重复特征因素,包括月经情况、术后病理的Ｔ分期、Ｎ分期、受体的免疫组化分型、术后放疗、化疗及内分泌治疗,采用Ｃｏｘ风险回归模型分析影响无复发生存率（ＲＦＳ）和总生存率（ＯＳ）的预后因素。对具有统计学意义的独立预后因素进行分层分析及Ｋａｐｌａｎ Ｍｅｉｅｒ生存曲线分析。结果：本组病例中Ｎ分期是影响患者ＲＦＳ及ＯＳ的独立因素,相对危险度（ＯＲ）分别为１.４５３（９５％ＣＩ：１.０９６～１.９２６,Ｐ＜０.０１）、１.４５８（９５％ＣＩ：１.０９９～１.９９３,Ｐ＜０.０１）。对Ｎ分期进行分层分析及Ｋａｐｌａｎ Ｍｅｉｅｒ生存曲线分析表明,Ｎ０期患者的ＲＦＳ及ＯＳ优于Ｎ１～Ｎ３期患者（Ｐ＜０.０５）,而Ｎ１～Ｎ３期患者之间ＲＦＳ及ＯＳ无差异（Ｐ＞０.０５）。结论：乳腺癌术后患者Ｎ分期与患者的预后有关,淋巴结阴性患者的预后好于淋巴结阳性患者预后,建议对淋巴结阳性患者加强术后辅助治疗。     

Coexpression of cyclin D1 and retinoblastoma gene product (pRb) in human squamous cell lung carcinomas is associated with increased tumor take rate in nude mice

Samples from 72 squamous cell lung carcinomas were analyzed immunohistochemically for the expression of cyclin D1 and pRb. Expression of cyclin D1 was found in 61% and expression of pRb in 39% of the cases. The take rate of human squamous cell lung carcinomas in nude mice was significantly different according to the expression of cyclin D1 and expression of pRb in primary human tumors [cyclin D1-negative (32%) vs. cyclin D1-positive (59%); P=0.026; pRb-negative (34%) vs. pRb-positive (71%); P=0.002]. The take rate was improved by coexpression of both proteins [both proteins negative/both proteins positive: 12% vs. 80% (P=0.00005)]. An association of the take rate and clinical parameters (age, extent of tumors, lymph node involvement, stage) could not be observed. Coexpression of cyclin D1 and pRb is also a prognostic factor for the patients' survival.     

ER和PR阴性乳腺癌雄激素受体与HER2表达相关性及其临床意义

目的 激素受体阴性(ER-/PR-)乳腺癌具有明显的肿瘤异质性,临床治疗手段相对有限.本研究探讨激素受体阴性乳腺癌组织中,雄激素受体(androgen receptor,AR)和HER2表达的相关性,及其与临床病理参数和预后的相关性.方法 收集中国人民解放军福州总医院经手术治疗并病理确诊的乳腺癌120例,中位年龄52岁.采用FISH法检测收集的激素受体阴性乳腺癌组织HER2/neu基因状态,分为HER2阳性(HER2过表达组)和HER2阴性(三阴组)两组,每组60例.并采用EliVisionTM plus免疫组化法检测AR、Ki-67、EGFR表达,分析HER2和AR表达与临床病理参数、3年无病生存期(disease free survival,DFS)的相关性.结果 AR在激素受体阴性乳腺癌组织阳性率为61.67％(74/120),HER2过表达组和三阴组分别为73.33％(44/60)和50.00％(30/60).激素受体阴性乳腺癌组织中,AR表达与月经状态、肿瘤大小、组织学分级、EGFR表达及HER2状态相关,均P值＜0.05;在HER2过表达组中,AR表达与月经状态、淋巴结受累、EGFR表达相关,均P值＜0.05;三阴组中,AR表达与肿瘤大小和组织学分级相关,均P值＜0.05.Kaplan-Meier法分析显示,HER2过表达组中AR表达与患者的3年DFS呈正相关,P＜0.05;Cox回归法分析结果示,肿瘤大小、淋巴结受累、EGFR表达、AR表达均与患者的3年DFS有关,P＜0.05.结论 AR可能成为筛选激素受体阴性乳腺癌高危人群和预测其预后的辅助指标之一,可作为激素受体阴性乳腺癌的新治疗靶点,为不同HER2状态乳腺癌治疗提供新思路.     

TopoⅡα蛋白在不同分子亚型乳腺癌中的表达及其预后价值

  目的  探讨拓扑异构酶Ⅱ(TopoisomeraseⅡ, TopoⅡα)蛋白在三阴性乳腺癌和HER2高表达型乳腺癌中的表达及其与预后的关系。  方法  选取2004年1月至7月天津医科大学附属肿瘤医院乳腺癌患者202例为研究对象, 其中三阴性乳腺癌101例, HER2高表达型乳腺癌101例, 采用免疫组化方法检测TopoⅡα蛋白在两型乳腺癌中的表达及其与预后的关系。  结果  TopoⅡα蛋白在三阴性乳腺癌中的表达率为51.9%, 在HER2过表达型乳腺癌中的表达率为48.9%, 二者差异无统计学意义(P>0.05)。TopoⅡα蛋白表达水平与两型乳腺癌患者月经状况、肿瘤大小、临床分期、腋下淋巴结转移状况、组织学分级、病理学类型等临床病理指标均无相关性(P>0.05)。HER2高表达型乳腺癌中, TopoⅡα蛋白阳性和阴性组5年无瘤生存率为81.0%和60.5%, 5年总生存率分别为92.1%和76.3%, 两组差异均具有统计学意义(P=O.037, P=0.047)。多因素分析结果显示TopoⅡα蛋白表达可以作为HER2过表达型乳腺癌的独立预后因子。三阴性乳腺癌中, TopoⅡα蛋白阳性和阴性组5年无瘤生存率分别为69.7%和82.4%, 差异具有统计学意义(P=0.044), 5年总生存率分别为75.0%和84.5%, 二者差异无统计学意义(P=0.927)。  结论  HER2过表达型乳腺癌, TopoⅡα蛋白阳性的患者预后较好, 提示此型乳腺癌患者可从蒽环类化疗药物中获益, 为临床用药提供一定的理论依据在三阴性乳腺癌患者中, TopoⅡα蛋白阳性表达患者较TopoⅡα蛋白阴性预后差, 对于临床判断预后具有指导意义。      

Clinicopathological features and treatment sensitivity of elderly Chinese breast cancer patients

This study aimed to determine the clinicopathological features and treatment sensitivity of elderly breast cancer patients in China. The clinical data of 594 elderly breast cancer patients of 70 or more years of age were collected and compared to those of 657 patients of less than 70 years of age to analyze whether breast cancer in the elderly is different and whether the difference affected outcome. The median age was 75.2 years in the elderly patients and 49.8 years in the young patients. Age of menarche, parous status and body mass index were similar in the two groups. A higher frequency of steroid receptor-positive rate, a lower expression of HER-2 and p53, less axillary node-positive rate and earlier tumor stage were found in patients of 70 years or older. The 5-year relapse-free survival (RFS) and overall survival (OS) was 77 and 82% in the elderly and 86 and 93% in the young patients, respectively. Patients with estrogen receptor (ER)-positive or lymph node (LN)-negative cancers showed a more favorable outcome in the elderly patients. RFS and OS were increased in elderly patients who underwent endocrine therapy or omitted chemotherapy. Breast cancer in the elderly had more favorable tumor features, using estrogen receptor and lymph node status as prognostic factors. It was therefore concluded that adjuvant endocrine therapy may benefit elderly patients, while chemotherapy may not.     

Role of COX-2, VEGF and cyclin D1 in mammary infiltrating duct carcinoma

Cyclooxygenase-2 (COX-2) has an important role in the promotion of carcinogenesis, tumor invasion and angiogenesis. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that is up-regulated in various tumors. VEGF has been shown to interact with COX-derived prostaglandins in angiogenesis. Cyclin D1 gene overexpression and amplification have been shown to play a role as prognostic factors in many human cancers. To better understand the roles of these genes in mammary carcinoma, the immunohistochemical expression patterns of COX-2 and VEGF were evaluated in relationship with cyclin D1 overexpression, tumor stage, clinicopathologic parameters and patient survival in 128 mammary infiltrating duct carcinomas. The expressions of COX-2/VEGF, COX-2/cyclin D1, and VEGF/cyclin D1 were evaluated using double immunofluorescein staining with a confocal scanning laser microscope. A positive expression was seen in 41% for COX-2, 47% for VEGF, and 66% for cyclin D1 in the cases with breast cancer. There was correlation in positive expression of COX-2 or VEGF with histologic grade, lymph node metastasis, and tumor size. Conversely, a significant inverse relation was observed between VEGF and patient age. There was a correlation in overexpression of cyclin D1 with lymph node metastasis, survival rate and survival length. Significant correlations were observed between COX-2 and VEGF as well as COX-2 and cyclin D1. Co-expression of only COX-2 and VEGF was detected with significance. These results indicate that elevated COX-2 or VEGF expression or cyclin D1 overexpression is more common in breast cancer patients with poor prognostic characteristics and is partly associated with an unfavorable outcome. The present findings support the efforts to initiate clinical trials on the efficacy of COX-2 inhibitors in adjuvant treatment of breast cancer.     

三阴性乳腺癌的临床病理特征及预后分析

目的 探讨三阴性乳腺癌(TNBC)患者的临床病理特点、生存情况和预后影响因素.方法 收集免疫组化检测雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER-2)均阴性的108例乳腺癌患者的临床病理资料,观察其长期生存状况.结果 中位发病年龄47岁.108例TNBC患者中,有乳腺癌家族史者8例,卵巢癌家族史者3例,自身曾患卵巢癌者1例.浸润性导管癌占87.0%,组织学分级多为Ⅱ、Ⅲ级.T1、T2期患者占92.6%,有淋巴结转移的患者占49.1%,Ⅰ、Ⅱ期患者占75.0%.5年无病生存率、无远处转移生存率、无局部复发生存率和总生存率分别为68.1%、70.9%、72.1%和76.9%.单因素分析结果显示,淋巴结转移、脉管瘤栓与TNBC预后有关.多因素分析结果显示,淋巴结转移是TNBC预后的独立影响因素(RR=5.944,P=0.001).结论 TNBC在我国的发病情况与白色人种相当,较黑色人种低.散发性乳腺癌可能是我国TNBC发病的主体.淋巴结转移是TNBC的独立预后影响因素.经放疗和以蒽环类药物为主的化疗后,我国TNBC患者的生存率与白色人种患者接近,较黑色人种患者高.     

Bcl-2 protein expression in breast cancer and its relationship to prognosis

The expression of bcl-2 protein was studied in invasive breast cancer by immunohistochemistry. Fourty-six (56.8%) bcl-2 protein-positive tumors were found in 81 breast cancers. There was no significant correlation between the bcl-2 protein immunoreactivity and histologic type, primary tumor status, or lymph node metastasis. However, a strong positive relationship was demonstrated between bcl-2 immunoreactivity and estrogen receptor status. The 5-year survival rate and disease-free survival rates were 73.7% and 71.1% of patients with bcl-2-positive tumors, and 62.5% and 58.0% of those with bcl-2-negative tumors; these differences between the two groups of patients wete significant (p<0.05). In multivariate analysis using Cox regression model, bcl-2 immunoreactivity emerged as an independent prognostic indicator in breast cancer patients.     

MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency

Breast cancer is a complex disease; the molecular mechanisms involved in sporadic breast carcinogenesis remain to be elucidated. The present study aimed to explore the deficiency of breast cancer susceptibility gene 1 (BRCA1), including protein loss expression, promoter hypermethylation and gene copy deletion, its correlationship with other tumor markers expression (TP53, MYC, etc.), and clinical significance in sporadic breast cancer. BRCA1 protein expression was negative in 226 of 374 (60.4 %) cases of this study. Cases negative for BRCA1 protein were more often with pathological tumor–node–metastasis stage III, positive for lymph node metastasis and MYC overexpression than BRCA1-positive tumors. BRCA1 hypermethylation was detected in 16.4 % (31 of 189) breast cancers, which correlated with BRCA1 negative, ER negative, MYC overexpression, and triple-negative phenotype. In addition, the percentage of cells with BRCA1 gene copy deletion was significantly increased in BRCA1-methylated tumors. Kaplan–Meier survival analysis showed that patients with BRCA1-negative expression showed a worse overall survival (OS) than those with BRCA1-positive expression, and patients with BRCA1-methylated tumors had a significantly worse disease-free survival than did patients with unmethylated tumors. Furthermore, BRCA1 hypermethylation showed an inverse association with OS in LN-positive or p53-negative subgroup patients. Importantly, uni- and multivariate Cox regression analyses revealed that BRCA1 was an independent prognostic indicator of OS in sporadic breast cancer. Thus, we found MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. The targeting of BRCA1 deficiency in combination with MYC–pathways inhibitors may provide a promising strategy for sporadic breast cancer care, the triple-negative subtype in particular.     

T1期HER2阳性乳腺癌患者临床特征及抗HER2靶向治疗对预后的影响分析

目的 总结T1期HER2阳性乳腺癌患者的临床病理特征,并分析抗HER2靶向治疗对预后的影响.方法 选取T1期HER2阳性乳腺癌患者50例,总结其临床病理特征,运用统计学方法分析影响患者预后的因素及抗HER2靶向治疗与患者预后关系.结果50例患者中T1a~1b期共13例(26%),T1c期共37例(74%),共4例出现复发转移,无死亡,总随访时间6~36个月,中位随访时间22个月;不同组织学分级、临床分期、脉管是否浸润、腋窝淋巴结是否转移、Ki-67是否为阳性、是否接受抗HER2靶向治疗的T1a~1b期与T1c期患者例数比较,差异有统计学意义(P﹤0.05);与未接受抗HER2靶向治疗患者(无病生存率为89.7%)相比,接受完整抗HER2靶向治疗患者3年内无患者出现复发转移(无病生存率为100.0%),差异有统计学意义(P=0.046);脉管浸润组及腋窝淋巴结转移组中是否接受靶向治疗患者的无病生存率比较,差异有统计学意义(P﹤0.05);Cox多因素分析显示腋窝淋巴结是否转移是影响T1期HER2阳性乳腺癌患者预后的独立因素.结论 T1期HER2阳性乳腺癌患者是否有腋窝淋巴结转移是其预后的独立影响因素,抗HER2靶向治疗对T1期HER2阳性乳腺癌伴随脉管转移或腋窝淋巴结转移患者预后较好.     

Studies on recurrent breast cancer--clinicopathological factors and p53, p21Cip1/Waf1 and cyclin D1 protein expression

Of patients radically operated on for breast cancer in our department, 46 patients who had recurrent breast cancer were clinicopathologically evaluated to clarify the prognostic factors of recurrent breast cancer. Furthermore, p53, p21 and cyclin D1 protein expression were studied immunohistochemically and their prognostic value was evaluated. The relapse-free interval was highly related to the survival rate after the recurrence. p53 overexpression was correlated with the progression of clinical stage and lymph node metastasis and negatively correlated with the expression of estrogen receptor. The p21 positive and p53 negative cases had a significantly better prognosis than the p21 negative and p53 positive cases. The combination of p53 and p21 protein expression seemed to have prognostic value in recurrent breast cancer.     

Luminal 型乳腺癌 P53表达与临床病理特征及预后的关系

目的：探讨 Luminal 型乳腺癌 P53表达与临床病理特征及预后的关系。方法选取2009年1月至2012年12月在上海交通大学附属第一人民医院手术治疗的283例 Luminal 型乳腺癌患者作为研究对象,采用免疫组织化学法测定 P53表达。生存分析采用 Kaplan-Meier 曲线评估和 Log-rank 检验比较,并用 Cox 比例风险回归模型进行单因素和多因素分析。结果 Luminal 型乳腺癌患者 P53表达与肿瘤最大径（χ2＝6．285,P ＝0．043）、淋巴结转移（χ2＝15．881,P ＝0．000）、组织分级（χ2＝8．132,P ＝0．043）、Ki-67（χ2＝6．476,P ＝0．039）有关;而与年龄（χ2＝0．955,P ＝0．328）、月经状态（χ2＝3．808,P ＝0．051）、病理类型（χ2＝0．847,P ＝0．655）、雌激素受体（χ2＝1．867,P ＝0．172）、孕激素受体（χ2＝0．937, P ＝0．333）及人表皮生长因子受体-2（χ2＝0．110,P ＝0．741）无关。在283例患者中,P53阴性组和阳性组5年无复发生存率分别为90．7％、66．7％（χ2＝12．609,P ＝0．000）,5年总生存率分别为93．4％、84．4％（χ2＝4．153,P ＝0．042）,差异均有统计学意义。Cox 多因素分析发现,淋巴结转移（HR ＝2．484,95％CI 为1．393～4．431,χ2＝9．497,P ＝0．002）和 P53阳性（HR ＝3．627,95％CI 为1．061～12．401;χ2＝4．220,P ＝0．040）是 Luminal 型乳腺癌患者无复发生存的独立危险因素;淋巴结转移（HR ＝3．451,95％CI为1．891～6．297;χ2＝16．290,P ＝0．000）和高组织学分级（HR ＝2．806,95％CI 为1．091～7．219;χ2＝4．582,P ＝0．032）是总生存时间的独立危险因素。结论 Luminal 型乳腺癌患者 P53过表达与淋巴结转移、组织分级等预后因素相关,且 P53过表达患者预后更差。     

132例三阴性乳腺癌患者的临床特征与预后分析

目的探讨三阴性乳腺癌的临床特征及影响预后的因素。方法采用回顾性方法对我院132例三阴性乳腺癌患者的临床特征进行分析,并根据随访资料分析了患者的生存情况及预后因素。所有患者均经免疫组化证实ER、PR、Her-2为阴性。结果132例三阴性乳腺癌患者占同期乳腺癌患者（774例）的17．1％,绝经前患者（91例）占68．9％,53．8％的患者（71例）发病时肿块大小为T2,39．4％患者（52例）腋窝淋巴结阳性。中位随访时间63个月,共有33例出现复发或转移,其中20例死亡,23例同时出现2个部位以上的转移,5年的无病生存率为73．8％,总生存率为85．7％。淋巴结阳性患者复发转移风险较淋巴结阴性患者明显增加（P=0．001）。结论三阴性乳腺癌患者大多在治疗后2—3年发生多发转移,仅淋巴结状况是影响其预后的重要因素,淋巴结阳性的三阴性乳腺癌患者预后差。     

High survivin mRNA expression is a predictor of poor prognosis in breast cancer: a comparative study at the mRNA and protein level

Background

Survivin plays a key role in the initiation and progression of breast cancer. However, its prognostic relevance to breast cancer patients has long been a matter of debate. The purpose of this study was to examine the expression of survivin and its role in predicting clinical outcome in a series of human breast cancer cases both at the mRNA and protein level.

Methods

Formalin-fixed paraffin-embedded tumor tissues from 245 female patients with invasive breast cancer and 13 patients with ductal carcinoma in situ were examined for survivin mRNA by quantitative real-time RT-PCR (RT-qPCR). In addition, 237 of these tumors with invasive breast cancer were available for immunohistochemistry (IHC). The relationship between survivin status and clinicopathological characteristics and prognosis was evaluated.

Results

RT-qPCR revealed that high levels of survivin mRNA were strongly associated with high nuclear grade, positive axillary lymph nodes, negative hormone receptor status, positive Her2 amplification, higher Ki67 labeling index, and presence of vascular invasion. In the Cox proportional regression model analysis, survivin mRNA was shown to be a significant univariate parameter for relapse-free survival (RFS), distant relapse-free survival (DRFS), and breast cancer-specific survival (BCSS) as well as a significant multivariate parameter for RFS, DRFS, and BCSS. In hormone receptor (HR)-positive/Her2-negative subtype cases, survivin mRNA expression was also an independent predictor in terms of DRFS. Immunohistochemically, positive staining was seen in the cytoplasm and/or nucleus of cancer cells, although this did not correlate with the mRNA level, and harbored no prognostic value.

Conclusions

High mRNA expression of survivin was an independent marker of poor prognosis both in the entire cohort and in the HR-positive/Her2-negative subtype, whereas the protein expression of survivin was not. These findings suggest that RT-qPCR can provide more reliable data than IHC in validating the prognostic significance of survivin for breast cancer patients.     

单中心非转移性男性乳腺癌临床病理特征和生存分析

Heʼnan Medical Team has stationed in Lin county(now Linzhou City) of Heʼnan Province for 60 years since November 1959 to carry out prevention and treatment research on high incidence of esophageal cancer. In the past 60 years, three generations of medical experts in Heʼnan Province have made a series of remarkable scientific research achievements in the molecular mechanism and early detection of esophageal cancer, intervention and prevention methods of precancerous lesions, and benefited thousands of patients. Based on the 34-year research of esophageal cancer prevention and treatment in our research group, this paper focuses on the understanding and thinking about the epidemic characteristics, key scientific issues and important research directions of esophageal cancer in China, so as to provide a reference for the prevention and treatment of esophageal cancer. © 2020, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.     

RNA甲基转移酶BCDIN3D的表达与乳腺癌预后的关系

目的探讨RNA甲基转移酶BCDIN3D的表达与乳腺癌患者预后的关系。方法选取2013年6月至2015年1月重庆市红十字会医院收治的乳腺癌患者80例,年龄19～65(467±47)岁;分子分型Luminal A、Luminal B、ERBB2+、Basal like型分别10、32、20、18例;肿瘤分期T0～1、T2、T3分别9、34、37例;淋巴结分期N0～1、N2、N3分别9、38、33例。均行标准乳腺癌改良根治术,术中获取乳腺癌组织标本,采用免疫组织化学法(IHC)检测乳腺癌组织中BCDIN3D的表达情况。对患者进行随访,统计总生存期(OS)。采用COX比例风险模型分析乳腺癌患者预后的影响因素。结果80例乳腺癌患者中,BCDIN3D阳性表达者30例(375％);BCDIN3D阴性表达者50例(625％)。BCDIN3D阳性表达者与BCDIN3D阴性表达者间肿瘤分期和淋巴结分期差异有统计学意义(P<005),不同年龄、月经状态、分子分型差异均无统计学意义(P>005)。中位随访时间为42(23～64)个月,Kaplan Meier分析结果显示,BCDIN3D阳性表达者、BCDIN3D阴性表达者的中位OS分别为412(95％CI:312～469)、495(95％CI:421～516)个月,BCDIN3D阳性表达者的OS短于BCDIN3D阴性表达者(χ2=25241,P<0001)。COX分析结果显示,肿瘤分期、淋巴结分期、分子分型、BCDIN3D表达是影响乳腺癌患者OS的独立预后因素(P<005)。结论BCDIN3D阳性表达与乳腺癌患者预后不良有关。