Prognostic value of paraaortic lymph node metastases in patients with ductal adenocarcinoma of the pancreatic head

IntroductionThe role of paraaortic lymphadenectomy for cancer of the pancreatic head is controversial. The aim of this study is to analyze the prognostic role of paraaortic lymph node (PALN) metastases after resection for ductal adenocarcinoma of the pancreatic head.Materials and methodsA retrospective analysis of all patients, who underwent upfront resection for ductal adenocarcinoma of the pancreatic head at the Frankfurt University Hospital from 2011 to 2020 was performed. The primary endpoint was survival, according to the presence of PALN metastases.ResultsOut of 468 patients with pancreatic resection, 148 had an upfront resection for ductal adenocarcinoma. Of those, in 125 (85%) a paraaortic lymphadenectomy was performed. In 19 (15.2%) PALN metastases were detected. The estimated overall median survival after resection was 21.7 months (95% CI 18.8 to 26.4), the disease free survival 16 months (95% CI 12 to 18). Among the patients with lymph node metastases, PALN metastases had no significant influence on overall (18.9 versus 19 months, HR = 1.3, 95% CI 0.7 to 2.6, p = 0.392) or disease free survival (14 versus 10.7 months, HR = 1.7, 95% CI 0.9 to 3.2, p = 0.076). After adjusting for T-stage, N-stage, grade, resection margin, PALN metastases, and adjuvant therapy, only adjuvant therapy had a prognostic significance for overall survival (HR = 0.47, 95% CI 0.26 to 0.85, p = 0.013).ConclusionPatients with ductal adenocarcinoma of the pancreatic head and PALN metastases do not have inferior outcomes than those with regional lymph node metastases. Thus, positive PALN should not be considered a contraindication for resection.     

Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: meta-analysis,experimental validation and clinical significance

Background

The diagnostic and prognostic value of microRNA (miRNA) expression aberrations in pancreatic ductal adenocarcinoma (PDAC) has been studied extensively in recent years. However, differences in measurement platforms and lab protocols as well as small sample sizes can render gene expression levels incomparable.

Methods

A comprehensive meta-review of published studies in PDAC that compared the miRNA expression profiles of PDAC tissues and paired neighbouring noncancerous pancreatic tissues was performed to determine candidate miRNA biomarkers for PDAC. Both a miRNA vote-counting strategy and a recently published Robust Rank Aggregation method were employed. In this review, a total of 538 tumour and 206 noncancerous control samples were included.

Results

We identified a statistically significant miRNA meta-signature of seven up- and three down-regulated miRNAs. The experimental validation results showed that the miRNA expression levels were in accordance with the meta-signature. The results from the vote-counting strategy were consistent with those from the Robust Rank Aggregation method. The experimental validation confirmed that the statistically unique profiles identified by the meta-review approach could discriminate PDAC tissues from paired nonmalignant pancreatic tissues. In a cohort of 70 patients, the high expression of miR-21 (p=0.018, HR=2.610; 95% CI=1.179-5.777) and miR-31 (p=0.039, HR=2.735; 95% CI=1.317-6.426), the low expression of miR-375 (p=0.022, HR=2.337; 95% CI=1.431-5.066) were associated with poor overall survival following resection, independent of clinical covariates.

Conclusions

The identified miRNAs may be used to develop a panel of diagnostic and prognostic biomarkers for PDAC with sufficient sensitivity and specificity for use in a clinical setting.     

Brain metastasis in renal cancer patients: metastatic pattern,tumour-associated macrophages and chemokine/chemoreceptor expression

Background:

The mechanisms of brain metastasis in renal cell cancer (RCC) patients are poorly understood. Chemokine and chemokine receptor expression may contribute to the predilection of RCC for brain metastasis by recruitment of monocytes/macrophages and by control or induction of vascular permeability of the blood–brain barrier.

Methods:

Frequency and patterns of brain metastasis were determined in 246 patients with metastatic RCC at autopsy. Expression of CXCR4, CCL7 (MCP-3), CCR2 and CD68⁺ tumour-associated macrophages (TAMs) were analysed in a separate series of 333 primary RCC and in 48 brain metastases using immunohistochemistry.

Results:

Fifteen percent of 246 patients with metastasising RCC had brain metastasis. High CXCR4 expression levels were found in primary RCC and brain metastases (85.7% and 91.7%, respectively). CCR2 (52.1%) and CCL7 expression (75%) in cancer cells of brain metastases was more frequent compared with primary tumours (15.5% and 16.7%, respectively; P<0.0001 each). The density of CD68⁺ TAMs was similar in primary RCC and brain metastases. However, TAMs were more frequently CCR2-positive in brain metastases than in primary RCC (P<0.001).

Conclusion:

Our data demonstrate that the monocyte-specific chemokine CCL7 and its receptor CCR2 are expressed in tumour cells of RCC. We conclude that monocyte recruitment by CCR2 contributes to brain metastasis of RCC.     

直肠良恶性肿瘤中肿瘤相关巨噬细胞和微血管及淋巴管生成的关系

目的:探讨直肠良恶性肿瘤组织中微血管密度(MVD)及淋巴管密度(LVD)与肿瘤相关巨噬细胞(TAMs)数量的相关性。方法:采用免疫组化的方法,用CD68标记TAMs,分别用CD31和D2-40标记微血管和淋巴管,光镜下对TAMs,MVD及LVD进行计数,分析。结果:直肠腺癌组织中的TAMs,MVD及LVD计数明显高于直肠腺瘤型息肉组织(P<0.01);在直肠腺癌组中,TAMs与MVD和LVD有明显相关性(TAMs与MVD:P<0.01;TAMs与LVD:P<0.01),且MVD与直肠癌淋巴结转移(P<0.01)和分化程度(P<0.05)密切相关;而TAMs和LVD仅与淋巴结转移有显著相关性(P<0.01,P<0.05)。结论:TAMs,MVD及LVD可能是反映直肠腺癌发生、发展、转移及侵袭能力的生物学指标,TAMs在肿瘤中的浸润可能与肿瘤血管及淋巴管的生成有关。     

直肠良恶性肿瘤中肿瘤相关巨噬细胞和微血管及淋巴管生成的关系

目的：探讨直肠良恶性肿瘤组织中微血管密度（MVD）及淋巴管密度（LVD）与肿瘤相关巨噬细胞（TAMs）数量的相关性。方法：采用免疫组化的方法,用CD68标记TAMs,分别用CD31和D2-40标记微血管和淋巴管,光镜下对TAMs,MVD及LVD进行计数,分析。结果：直肠腺癌组织中的TAMs,MVD及LVD计数明显高于直肠腺瘤型息肉组织（P〈0.01）;在直肠腺癌组中,TAMs与MVD和LVD有明显相关性（TAMs与MVD：P〈0.01;TAMs与LVD：P〈0.01）,且MVD与直肠癌淋巴结转移（P〈0.01）和分化程度（P〈0.05）密切相关;而TAMs和LVD仅与淋巴结转移有显著相关性（P〈0.01,P〈0.05）。结论：TAMs,MVD及LVD可能是反映直肠腺癌发生、发展、转移及侵袭能力的生物学指标,TAMs在肿瘤中的浸润可能与肿瘤血管及淋巴管的生成有关。     

microRNAs with prognostic significance in pancreatic ductal adenocarcinoma: A meta-analysis

BackgroundReports have described the prognostic relevance of microRNAs (miRNAs) in patients treated for pancreatic ductal adenocarcinoma (PDAC). However, many of these include small numbers of patients. To increase statistical power and improve translation, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of miRNAs on overall survival (OS) and disease-free survival (DFS) in PDAC.MethodsEligible studies were identified and quality assessed using multiple search strategies (last search December 2014). Data were collected from studies correlating clinical outcomes with dysregulated tumoural or blood miRNAs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.ResultsTwenty studies involving 1525 patients treated for PDAC were included. After correcting for publication bias, OS was significantly shortened in patients with high tumoural miR-21 (adjusted HR = 2.48; 1.96–3.14). This result persisted when only studies adjusting for adjuvant chemotherapy were combined (adjusted HR = 2.72; 1.91–3.89). High miR-21 also predicted reduced DFS (adjusted HR = 3.08; 1.78–5.33). Similarly, we found significant adjusted HRs for poor OS for high miR-155, high miR-203, and low miR-34a; and unadjusted HRs for high miR-222 and high miR-10b. The small number of studies, limited number of miRNAs and paucity of multivariate analyses are the limitations of our study.ConclusionsThis is the first rigorous pooled analysis assessing miRNAs as prognostic biomarkers in PDAC. Tumoural miR-21 overexpression emerged as an important predictor of poor prognosis after PDAC resection independent of other clinicopathologic factors, including adjuvant chemotherapy use.     

Targeting the tumor microenvironment in pancreatic ductal adenocarcinoma

Introduction: The dismally slow improvement in patient survival over the years for pancreatic cancer patients is mainly due to two factors: the late diagnosis, at which point the disease is spread to distant organs; and the fact that tumor cells are surrounded by a dense, highly immunosuppressive microenvironment. The tumor microenvironment not only shields pancreatic cancer cells from chemotherapy but also leaves it unsusceptible to various immunotherapeutic strategies that have been proven successful in other types of cancer.

Areas covered: This review highlights the main components of the pancreatic tumor microenvironment, how they cross-talk with each other to generate stroma and promote tumor growth. Additionally, we discuss the most promising treatment targets in the microenvironment whose modulation can be robustly tested in combination with standard of care chemotherapy. Currently, active clinical trials for pancreatic cancer involving components of the microenvironment are also listed.

Expert opinion: Although immunotherapeutic approaches involving checkpoint inhibition are being pursued enthusiastically, there is still more work to be done with several other emerging immune targets that could provide therapeutic benefit.     

Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

Tumour-associated macrophages, TAMs, play a pivotal role in tumour growth and metastasis by promoting tumour angiogenesis. Treatment with clodronate encapsulated in liposomes (clodrolip) efficiently depleted these phagocytic cells in the murine F9 teratocarcinoma and human A673 rhabdomyosarcoma mouse tumour models resulting in significant inhibition of tumour growth ranging from 75 to >92%, depending on therapy and schedule. Tumour inhibition was accompanied by a drastic reduction in blood vessel density in the tumour tissue. Vascular endothelial growth factor (VEGF) is one of the major inducers of tumour angiogenesis and is also required for macrophage recruitment. The strongest effects were observed with the combination therapy of clodrolip and a VEGF-neutralising antibody, whereas free clodronate was not significantly active. Immunohistologic evaluation of the tumours showed significant depletion of F4/80+ and MOMA-1+ and a less pronounced depletion of CD11b+ TAMs. Blood vessel staining (CD31) and quantification of the vessels as well as TAMs and tumour-associated dendritic cells (TADCs) in the A673 model showed reduction rates of 85 to >94%, even 9 days after the end of therapy. In addition, CD11c+ TADCs, which have been shown to potentially differentiate into endothelial-like cells upon stimulation by tumour released growth and differentiation factors, were similarly reduced by clodrolip or antibody treatment. These results validate clodrolip therapy in combination with angiogenesis inhibitors as a promising novel strategy for an indirect cancer therapy aimed at the haematopoietic precursor cells that stimulate tumour growth and dissemination and as a tool to study the role of macrophages and dendritic cells in tumorigenesis.     

远端胃癌淋巴结转移规律及临床意义*

目的：探讨远端胃癌各组淋巴结转移的特点,指导远端胃癌根治手术中淋巴结清扫的范围。方法：回顾性分析2010年2 月至2014年9 月天津医科大学肿瘤医院远端胃癌患者773 例接受D 2（D 2 +）胃次全切除术的临床病理资料,分析其淋巴结转移特点。结果：773 例远端胃癌患者术后病理证实淋巴结转移为423 例（54.72%）,各组淋巴结中发生转移的患者所占比例由高至低依次为NO.6、NO.3、NO.4sb 、NO.5 组淋巴结。N 1 淋巴结转移率由高至低依次为NO.3、NO.6、NO.5、NO.4d 组淋巴结;N 2 淋巴结转移率由高至低依次为NO.8a 、NO.7、NO.1 组淋巴结。50.68% 的患者出现NO.8a 组淋巴结跳跃性转移。结论：远端胃癌根治性手术应注意NO.8a 淋巴结转移的可能性,必要时应适当扩大淋巴结的清扫范围。     

Post-therapy pathologic stage and survival in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation

BACKGROUND:

Neoadjuvant chemoradiation before surgery is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC). However, analysis of prognostic factors is limited for patients with PDAC treated with neoadjuvant chemoradiation and pancreaticoduodenectomy (PD).

METHODS:

The study population was comprised of 240 consecutive patients with PDAC who received neoadjuvant chemoradiation and PD and was compared with 60 patients who had no neoadjuvant therapy between 1999 and 2007. Clinicopathologic features were correlated with disease‐free survival (DFS) and overall survival (OS).

RESULTS:

Among the 240 treated patients, the 1‐year and 3‐year DFS rates were 52% and 32%, with a median DFS of 15.1 months. The 1‐year and 3‐year OS rates were 95% and 47%, with a median OS of 33.5 months. By univariate analysis, DFS was associated with age, post‐therapy tumor stage (ypT), lymph node status (ypN), number of positive lymph nodes, and American Joint Committee on Cancer (AJCC) stage, whereas OS was associated with intraoperative blood loss, margin status, ypT, ypN, number of positive lymph nodes, and AJCC stage. By multivariate analysis, DFS was independently associated with age, number of positive lymph nodes, and AJCC stage, and OS was independently associated with differentiation, margin status, number of positive lymph nodes, and AJCC stage. In addition, the treated patients had better OS and lower frequency of lymph node metastasis than those who had no neoadjuvant therapy.

CONCLUSIONS:

In patients with PDAC who received neoadjuvant chemoradiation and subsequent PD, post‐therapy pathologic AJCC stage and number of positive lymph nodes are independent prognostic factors. Cancer 2012. © 2011 American Cancer Society.     

E-cadherin在乳腺浸润性导管癌中的表达及临床意义

目的 探讨E-钙黏蛋白（E-cad）在乳腺浸润性导管癌中的表达及其与乳腺癌临床病理特征、淋巴结转移及预后的关系。方法 采用免疫组织化学 SP 法检测30例乳腺纤维腺瘤、450例乳腺浸润性导管癌组织中E-cad的表达,分析其表达与临床病理特征的关系, Kaplan-Meier法绘制生存曲线。结果E-cad在无淋巴结转移乳腺癌组织中阳性表达率为49.04％（77／157）,在有淋巴结转移的乳腺癌组织中阳性表达率为29.69％（87／293）,差异有统计学意义（P＜0.05）。E-cad表达与年龄、淋巴结转移、肿块大小、ER表达、分子分型及组织学分级有关（P＜0.05）,而与肿瘤分期、是否绝经、HER-2及Ki-67表达情况无关。乳腺癌淋巴结转移组、三阴性乳腺癌组中E-cad阳性表达者5年生存率优于E-cad阴性表达者,差异有统计学意义（P＜0.05）。结论 E-cad表达与乳腺癌淋巴结转移关系密切,其亦可成为乳腺癌伴淋巴结转移者或三阴性乳腺癌预后的判断指标。     

淋巴结切除术对子宫内膜癌的临床意义

手术治疗是子宫内膜癌的主要治疗方式,通过手术治疗可以明确诊断、病理分级、临床分期,并为术后的辅助治疗提供充分的临床资料。对于子宫内膜癌患者是否常规进行淋巴结切除仍存在较大争议,特别是对于低危的子宫内膜癌患者而言,因为低危患者淋巴结转移发生率非常低,且不影响患者的预后,但目前没有全面的划分淋巴结转移危险因素及其危险程度的统一标准。本文就子宫内膜癌的淋巴结转移特点,影响淋巴结转移的因素,淋巴结切除的并发症,淋巴结切除术对预后的影响,淋巴结切除的临床意义及淋巴结切除的发展方向等方面加以综述,我们认为对于内膜癌患者应选择个体化的治疗方案,注重术前的全面评估,对于G3,透明细胞,浸润肌层≥1/2,病灶>2cm,宫颈受累等应进行包括腹主动脉旁淋巴结在内的系统淋巴结切除术。     

MicroRNA in pancreatic ductal adenocarcinoma and its precursor lesions

Pancreatic ductal adenocarcinoma (PDAC) is the 4^th deadliest cancer in the United States, due to its aggressive nature, late detection, and resistance to chemotherapy. The majority of PDAC develops from 3 precursor lesions, pancreatic intraepithelial lesions (PanIN), intraductual papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm. Early detection and surgical resection can increase PDAC 5-year survival rate from 6% for Stage IV to 50% for Stage I. To date, there are no reliable biomarkers that can detect PDAC. MicroRNAs (miRNA) are small noncoding RNAs (18-25 nucleotides) that regulate gene expression by affecting translation of messenger RNA (mRNA). A large body of evidence suggests that miRNAs are dysregulated in various types of cancers. MiRNA has been profiled as a potential biomarker in pancreatic tumor tissue, blood, cyst fluid, stool, and saliva. Four miRNA biomarkers (miR-21, miR-155, miR-196, and miR-210) have been consistently dysregulated in PDAC. MiR-21, miR-155, and miR-196 have also been dysregulated in IPMN and PanIN lesions suggesting their use as early biomarkers of this disease. In this review, we explore current knowledge of miRNA sampling, miRNA dysregulation in PDAC and its precursor lesions, and advances that have been made in using miRNA as a biomarker for PDAC and its precursor lesions.     

Analysis of liver metastasis after resection for pancreatic ductal adenocarcinoma

AIM:To investigate the risk factors affecting the liver metastasis(LM) of pancreatic ductal adenocarcinoma(PDAC) after resection.METHODS:We retrospectively analyzed 101 PDAC patients who underwent surgical resection at the Samsung Medical Center between January 2000 and December 2004.Forty one patients with LM were analyzed for the time of metastasis,prognostic factors affecting LM,and survival.RESULTS:LM was found in 40.6%.The median time of the LM(n = 41) was 6.0 ± 4.6 mo and most LM occurred within 1 year.In univariate analysis,tumor size,preoperative carbohydrate antigen 19-9,and perineural invasion were factors affecting LM after resection.In multivariate analysis,tumor size was the most important factor for LM.In univariate analysis,tumor cell differentiation was significant to LM in low-risk groups.CONCLUSION:LM after resection of PDAC occurs early and shows poor survival.Tumor size is the key indicator for LM after resection.     

Reappraisal of nodal staging and study of lymph node station involvement in distal pancreatectomy for body-tail pancreatic ductal adenocarcinoma

BackgroundThe pattern of nodal spread in body-tail pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study analyzed the characteristics of lymph node (LN) involvement and the prognostic role of nodal metastases stratified by LN stations.MethodsAll upfront distal pancreatectomies (DPs) for PDAC (2000–2017) with complete information on station 8,10,11, and 18 were included. Clinico-pathological correlates and survival were investigated using uni- and multivariable analyses.ResultsAmong 100 included patients, 28 were N0, 42 N1 and 30 N2. The median number of examined LN was 32 (IQR 26–44). Tumor size at preoperative imaging increased across N-classes. Preoperative size >27.5 mm was associated with N2 status. The frequency of nodal metastases at stations 8, 9, 10, 11, and 18 was 12.0%, 10.9%, 3.0%, 71.0%, and 19%, respectively. The pattern of LN spread was independent from primary tumor location (with tail tumors metastasizing to station 8/9 and body tumors to station 10), while it was highly associated with N-class. At multivariable analysis, tumor grading, adjuvant treatment, station 9 and 10 metastases were independent prognostic factors in node-positive patients.ConclusionsIn patients undergoing upfront DP for PDAC preoperative tumor size is associated with the degree of nodal spread. While station 11 was the most frequently involved, only station-9 and 10 metastases were independent prognostic factors. The site of nodal metastases was somewhat unpredictable based on tumor location. This data has potential implications for allocating patients to neoadjuvant treatment and supports the performance of routine splenectomy during DP for PDAC.     

食管鳞状细胞癌组织Bin1基因启动子甲基化状态及其临床意义

目的:探讨食管鳞状细胞癌(esophageal squamous cell cancer,ESCC)患者的食管鳞癌组织、癌旁组织中Bin1基因启动子甲基化状态及其mRNA的表达及其临床意义.方法:采用实时荧光定量PCR(qRT-PCR)分别检测58例经病理证实的ESCC患者的食管鳞癌组织、癌旁组织中Bin1基因mRNA的表达情况;用甲基化特异性PCR(MSP)检测上述食管鳞癌组织中Bin1基因启动子甲基化状态,比较ESCC患者Bin1甲基化状态与临床病理分期的关系.结果:ESCC组织中Bin1基因启动子甲基化率明显高于癌旁组织(58.62％ vs 25.86％,x2=12.76,P＜0.01),Bin1甲基化状态与患者TNM分期、肿瘤侵润深度、分化程度、淋巴结转移相关(均P ＜0.05).ESCC组织中Bin1 mRNA的表达水平明显低于癌旁组织[(0.78 ±0.05) vs (1.03±0.03),t=9.643,P＜0.01)];发生Bin1甲基化的组织中Bin1 mRNA表达水平明显低于未发生甲基化的组织[(0.68±0.04) vs (0.85±0.07),t=2.476,P＜0.05].结论:Bin1基因启动子区甲基化状态可能与ESCC的发生密切相关,它是ESCC中Bin1 mRNA低表达或缺失的机制之一,且与ESCC进展和淋巴结转移有关.     

Skeletal metastases in advanced pancreatic ductal adenocarcinoma: a retrospective analysis

BackgroundSkeletal metastases (SM) in advanced pancreatic ductal adenocarcinoma (PDAC) is an infrequent occurrence that has been previously reported in literature to occur in less than 2.5% of the cases. Complications such as pathological fractures can result in intractable pain, immobilization and a significant deterioration in quality of life. The purpose of this study is to improve the understanding of the increasing incidence of SM and the importance of surveillance and adequate management of SM in these patients.MethodsA retrospective analysis was conducted using a clinical database at a single tertiary care institution for cancer patients; this included 207 patients with advanced PDAC diagnosed between December 2004 and March 2017 receiving palliative chemotherapy. SM were identified by computerized tomography (CT)/fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI). Information regarding demographics, clinical course and date of last follow-up/death were collected. After a median follow-up of 11 months, an analysis was conducted, including a Kaplan-Meier survival analysis.ResultsThe study included 207 patients; 19 out of 207 patients (9.2%) developed SM; the primary tumor was located in the pancreatic body/tail in 12 out of 19 patients (63.2%). The thoracic and lumbar vertebrae were the most common sites of SM. Other common synchronous sites of metastases included the liver and lung. A majority of the lesions were osteolytic (63.2%). The median time of diagnosis from the initial diagnosis was 2 months (range, 0–60 months). Bone pain was observed as the initial symptom in 7 out of 19 patients (36.8%), 2 out of 19 patients (10.5%) had a pathological fracture and 1 out of 19 patients (5.3%) developed a para-spinal mass causing inferior vena cava compression. The median survival period for patients with SM was 11 months (range, 0–62 months) and for those without SM was 12 months (range, 0–147 months) [hazard ratio (HR) 1.24, 95% confidence interval (CI): 0.66–2.30, P=0.51].ConclusionsThere has been a challenge with regards to management of the increasing number of patients with SM. Thoracic and lumbar vertebrae are the most common sites and pathological fractures in these sites can be catastrophic. Careful evaluation of skeletal signs and symptoms, early detection and intervention are essential to prevent morbidity and mortality from complications in patients with PDAC and SM.     

乳腺浸润性导管癌中Maspin、uPA的表达及其临床意义

目的：探讨乳腺浸润性导管癌组织中Maspin蛋白和尿激酶型纤溶酶原激活物（uPA）蛋白的表达及其临床意义。方法：应用免疫组织化学法检测60例乳腺浸润性导管癌组织中Maspin、uPA蛋白的表达情况,并对其与乳腺癌临床病理特征的关系进行统计学分析。结果：乳腺浸润性导管癌组织中Maspin蛋白的阳性表达率为46．7％,uPA蛋白的阳性表达率为61．7％,Maspin、uPA蛋白的表达存在显著负相关,r=-0．362,P〈0．01。结论：乳腺癌的发生、浸润和转移可能和Maspin蛋白表达下调及uPA表达上调相关,Maspin表达的下调或缺失使得uPA对肿瘤细胞介导的纤溶酶原激活抑制作用丧失,uPA表达上调,成为促进乳腺癌细胞的侵袭和转移的途径之一。     

Immunohistochemical analysis of p53 in colorectal cancer regarding clinicopathological correlation and prognostic significance

The overexpression of the tumor suppressor gene p53 was investigated immunohistochemically in 144 cases of primary colorectal cancer and in 8 cases with cancer in the corresponding metastatic lymph nodes. Abnormalities in p53 expression were found in 36 cases (25%) of the 144 primary cancer cases. In addition, p53-positive tumors were found to metastasize frequently to the lymph nodes, as compared to p53-negative tumors (61.1% vs. 41.7%, P=0.0428). p53 staining was identical in 7 of 8 (87.5%) cases in primary and metastatic lesions. When the DNA content of the tumor was determined by flow cytometry, the DNA index (mean ± SD) was significantly higher in p53-positive tumors than in p53-negative tumors (1.57 ± 0.38 vs. 1.39 ± 0.37, P=0.012). Therefore, the immunohistochemical data of p53 in colorectal cancer may help in potentially predicting metastatic spread to the lymph nodes. © 1995 Wiley-Liss, Inc.     

胃中部癌前哨淋巴结邻近、横向和跳跃性转移的临床分析

Objective: To investigate the distribution pathway of sentinel lymph nodes (SLN) in middle third gastric carci-noma, as the foundation for rational lymphadenectomy. Methods: 52 cases of middle third tumors with solitary lymph nodes from 1852 gastric carcinomas were selected. The locations and histological types of metastatic lymph nodes were analyzed retrospectively. Results: Of 52 solitary node metastases cases, 37 were limited to perigastric nodes (N1), while 15 with skipping metastasis. In the 35 cases with tumor of lesser curvature, there were 17 cases found lymph nodes of the lesser curvature side (No. 3), 5 cases involved lymph nodes of the greater curvature (No. 4), and 8 cases with lymph nodes of the left gastric artery (No. 7). In the 17 cases with tumor of greater curvature, 7 cases spread to No. 4, while 3 metastasized to lymph nodes of the spleen hilum (No. 10). The difference of the histological types in groups N1 and over N1, were not statistically significant (P > 0.05). Conclusion: Adjacent metastasis formed the primary distribution pattern of SLN in middle third gastric carcinoma, transversal and skipping metastases being also notable.