病理组织学生长方式对肝转移性结直肠癌患者术后3年无进展生存期的预测作用

目的探讨病理组织学生长方式对肝转移性结直肠癌患者肝转移瘤切除术后3年无进展生存期(PFS)的预测作用。方法收集2007年1月至2017年1月间北京大学人民医院收治的经病理确诊并进行手术完整切除的肝转移性结直肠癌患者111例的临床病理资料,排除不符合入组标准的病例,最后入组患者共80例。根据组织学生长方式国际专家共识标准,评估其肝转移瘤的组织学生长方式类型。通过χ²或Fisher确切检验分析组织学生长方式与其他临床病理因素的相关性。通过Kaplan-Meier生存曲线分析不同组织学生长方式的肝转移性结直肠癌患者3年PFS的差异,并通过单因素及多因素分析,确定影响其3年PFS的独立危险因素。结果共入组80例患者,其中促纤维组织增生型43例(54%)、替代型32例(40%)、推挤型3例(4%)、混合型2例(2%)。组织学生长方式与患者年龄、性别、转移瘤发生时间、肿瘤负荷、组织学分级、是否伴有黏液分化及微卫星不稳定性等临床病理特征无相关性(P>0.05)。促纤维组织增生型患者的3年PFS明显优于替代型患者,差异有统计学意义(χ²=6.107,P=0.013)。单因素及多因素分析均显示组织学生长方式为预后的独立影响因素。结论结直肠癌肝转移瘤组织学生长方式主要表现为促纤维组织增生型和替代型。组织学生长方式为肝转移性结直肠癌患者术后独立的预后因素,故组织学生长方式需要在病理报告中明确指出,以提示临床合理选择治疗策略。     

Combination of percutaneous radiofrequency ablation and systemic chemotherapy are effective treatment modalities for metachronous liver metastases from gastric cancer

This study evaluated the efficacy of percutaneous radiofrequency ablation (RFA) for the treatment of metachronous liver metastases of gastric cancer. We enrolled a total of 44 patients who underwent percutaneous RFA for the treatment of metachronous liver metastases after resection of a primary gastric adenocarcinoma from January 2002 to November 2011. The primary endpoint of this study was overall survival (OS) and recurrence-free survival (RFS) after RFA. Systemic chemotherapy was combined with RFA in 40 patients; the OS and RFS of the patients with liver-only metastasis who underwent RFA and chemotherapy were 20.9 months (95 % CI 18.4–23.4) and 9.8 months (95 % CI 9.2–10.5), respectively. On multivariate analysis, the factors independently, negatively associated with OS were extrahepatic metastatic lesions (HR 12.6, 95 % CI 3.7–42.9; p = 0.001), no chemotherapy (HR 43.3, 95 % CI 7.4–251.3; p = 0.001), and tumor number ≥2 (HR 2.6, 95 % CI 1.2–5.9; p = 0.015). The factors independently, negatively associated with RFS were extrahepatic metastatic lesions (HR 3.6, 95 % CI 1.6–7.8; p = 0.003) and bilobar intrahepatic distribution (HR 3.9, 95 % CI 1.5–9.9; p = 0.001). The efficacy of percutaneous RFA for metachronous liver metastases of gastric cancer is limited to patients with a single, unilobar metastasis without extrahepatic metastatic lesions. Combined systemic chemotherapy is very important for the prolongation of OS.     

Clinical and pathological features of metastases of primary cutaneous desmoplastic melanoma

Murali R, Zannino D, Synnott M, McCarthy S W, Thompson J F & Scolyer R A
(2011) Histopathology  58 , 886–895
Clinical and pathological features of metastases of primary cutaneous desmoplastic melanoma Aims: Primary cutaneous desmoplastic melanoma (DM) may be entirely desmoplastic [‘pure’ DM (pDM)] or exhibit a desmoplastic component admixed with a non‐desmoplastic component [‘combined’ DM (cDM)]. Our aim was to describe the histological features of metastases of primary DM and to determine whether they were predictive of outcome. Methods: The effect of clinicopathological parameters on overall survival (OS) was analysed, and the correlation between histological features of the primary melanoma and metastases was studied in patients with metastatic DM. Results: Twenty‐six patients (18 males; eight females) developed 50 metastases in sentinel nodes (13; 26.0%), regional nodes (10; 20.0%), skin (14; 28.0%), and distant sites (13; 26.0%). The cellular composition of metastases correlated with that of the corresponding primary tumours. Time to development of first non‐sentinel lymph node metastasis was shorter in cDM than in pDM (median 11.2 versus 24.9 months, P = 0.075). The only independent predictors of poorer OS were cDM type [hazard ratio 6.17, 95% confidence interval (CI) 1.61–23.81, P = 0.008] and male sex (hazard ratio 5.98, 95% CI 1.34–26.66, P = 0.019). Conclusions: The cellular composition of primary DM correlates with that of metastatic DM and with outcome. It is important to consider the possibility of primary or metastatic DM when examining tumours composed of spindle cells.     

Extracapsular extension but not the tumour burden of lymph node metastases is an independent adverse risk factor in lymph node-positive bladder cancer

Seiler R, von Gunten M, Thalmann G N & Fleischmann A
(2011) Histopathology  58 , 571–578
Extracapsular extension but not the tumour burden of lymph node metastases is an independent adverse risk factor in lymph node‐positive bladder cancer Aims: To evaluate risk factors in lymph node‐positive bladder cancer. Methods and results: Lymph node‐positive bladder cancer patients (n = 162), preoperatively staged N0M0, underwent cystectomy and standardized extended lymphadenectomy. Five‐year overall survival of the cohort was 33%. In univariate analysis, tumour stage (P < 0.006), extracapsular extension of lymph node metastases (P < 0.001), total diameter of metastases (P < 0.04) and lymph node stage (P < 0.03) were significantly correlated with overall survival (OS), disease‐specific survival (DSS) and recurrence‐free survival (RFS). On multivariate analysis, only extracapsular extension (OS, P < 0.002; DSS, P < 0.02; RFS, P = 0.058) and primary tumour stage (OS, P = 0.058; DSS, P < 0.02; RFS, P < 0.02) added independent prognostic information. Extracapsular extension of lymph node metastases did not correlate with a specific recurrence pattern; patients with organ‐confined tumours (pT1/2) never had pelvic relapse. Conclusions: Extracapsular extension of lymph node metastases but not lymph node tumour burden adds independent prognostic information in lymph node‐positive bladder cancer. These biological differences in lymph node‐positive bladder cancer are not reflected in the sixth, and challenge future, TNM classification.     

SPARC expression in desmoplastic and non desmoplastic pancreatic carcinoma and cholangiocarcinoma

BackgroundThe pancreatobiliary carcinomas are characterized by presence of desmoplastic stroma. Overexpression of secreted protein acid and rich in cysteine (SPARC), a matrix producing agent has been documented in pancreatic ductal adenocarcinomas, with survival benefits. This study was targeted to see if SPARC expression in pancreatobiliary carcinomas is responsible for stromal desmoplasia and its prognostic significance.MethodsIn this retrospective study 48 cases of pancreatic cancer and 27 cases of cholangiocarcinoma were analyzed. The expression pattern of SPARC and vascular endothelial growth factor (VEGF) (angiogenic factors) was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. Immunoreactivity was scored semi quantitatively based on stain intensity and stain distribution. SPARC expression was correlated with tumor histology, stromal desmoplasia, VEGF expression, various histological parameters and overall survival in patients. Real time polymerase chain reaction was performed in few cases to validate the immunohistochemistry expression pattern.ResultsSPARC expression was high in peritumoral stroma in pancreatic carcinoma than in pancreatic controls; however, SPARC expression pattern was not grossly different in desmoplastic and non-desmoplastic pancreatobiliary carcinomas and in cholangiocarcinomas. No definite correlation was noted between SPARC expression and histological markers of severity and overall survival data.ConclusionsThe relevance of SPARC expression in pancreato-biliary carcinomas though may still be important for therapeutic decision making, it is not responsible for peritumoral stromal desmoplasia in these tumors and it does not have any significant prognostic implication.     

Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models

Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre‐existing vessels from surrounding tissue (vessel co‐option). As anti‐angiogenic therapies were designed to target only new blood vessel growth, vessel co‐option has been proposed as a mechanism that could drive resistance to anti‐angiogenic therapy. However, vessel co‐option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti‐angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co‐option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co‐opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co‐opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co‐option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co‐option mediates resistance to the anti‐angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co‐option in lung metastases occurs through at least three distinct mechanisms, that vessel co‐option occurs frequently in lung metastases, and that vessel co‐option could mediate resistance to anti‐angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co‐option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

结直肠癌肝转移预测及预后的影像组学综述

结直肠癌在国内外都是高发病率和高死亡率的肿瘤疾病，肝脏是结直肠癌血行转移最主要的靶器官，尽早准确地预测结直肠癌肝转移的发生以及监测患者治疗的预后反应，对患者的诊断和治疗尤为关键。新兴的影像组学为精准预测结直肠癌肝转移以及评估预后提供新的可能。对现有的结直肠癌肝转移影像组学研究进行综述，首先介绍结直肠癌肝转移研究的临床意义以及现有研究存在的缺陷，然后阐述结直肠癌肝转移影像组学的分析流程，接着对结直肠癌肝转移影像组学的4个研究方向展开综述，包括肝转移病理生长模式预测、隐匿性肝转移预测、肝转移疗效预后评估、肝转移患者生存期预后评估；阐明各个方向的最新研究进展及存在的缺陷性；最后对结直肠癌肝转移影像组学的未来发展趋势进行展望。     

Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective,Multi-Institutional Study

PurposeTo identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC).ResultsWith a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy.ConclusionA preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.     

β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases

Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, β-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01–0.56) and high Ki67 (HR 3.68, 95 % CI 1.12–12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11–5.44). Additionally, the β-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02–4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed β-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis.     

Desmoplastic stromal reaction in papillary thyroid microcarcinoma

Koperek O, Asari R, Niederle B & Kaserer K
(2011) Histopathology  58 , 919–924
Desmoplastic stromal reaction in papillary thyroid microcarcinoma Aims: To evaluate the value of a desmoplastic stromal reaction (desmoplasia) as an indicator of metastasis in papillary thyroid microcarcinoma. Methods and results: One hundred and nine cases of papillary thyroid microcarcinoma from the pathological archive of the Medical University of Vienna, Austria were analysed for the presence of desmoplasia in relation to other morphological and clinicopathological parameters. Eighty‐one of 109 papillary microcarcinomas showed a desmoplastic stromal reaction. The desmoplasia was significantly associated with lymph node metastases (P = 0.001) and tumour diameter (P < 0.001). In addition, ‘invasive parameters’, such as peritumoral and vascular invasion, were associated with the presence of a desmoplastic stromal reaction (P < 0.001 and P = 0.006, respectively), and all pT3b tumours according to the UICC classification of 2002 (i.e. with perithyroidal infiltration) showed desmoplasia. Of all morphological parameters, the best indicator of lymph node metastasis was tumour calcification (P < 0.001). Conclusions: Our data indicate that a desmoplastic stromal reaction seems to be an indicator of invasive behaviour of papillary thyroid microcarcinomas significantly associated with lymph node metastases. Papillary microtumours without signs of invasion, e.g. desmoplasia, should not be regarded as invasive carcinoma, as they are more likely to be thyroidal intraepithelial neoplasias.     

Prognostic factors in lymph node metastases of prostatic cancer patients: the size of the metastases but not extranodal extension independently predicts survival

Aims: To analyse tumour characteristics and the prognostic significance of prostatic cancers with extranodal extension of lymph node metastases (ENE) in 102 node‐positive, hormone treatment‐naive patients undergoing radical prostatectomy and extended lymphadenectomy. Methods and results: The median number of nodes examined per patient was 21 (range 9–68), and the median follow‐up time was 92 months (range 12–191). ENE was observed in 71 patients (70%). They had significantly more, larger and less differentiated nodal metastases, paralleled by significantly larger primary tumours at more advanced stages and with higher Gleason scores than patients without ENE. ENE defined a subgroup with significantly decreased biochemical recurrence‐free (P = 0.038) and overall survival (P = 0.037). In multivariate analyses the diameter of the largest metastasis and Gleason score of the primary tumour were independent predictors of survival. Conclusions: ENE in prostatic cancer is an indicator lesion for advanced/aggressive tumours with poor outcome. However, the strong correlation with larger metastases suggests that ENE may result from their size, which was the only independent risk factor in the metastasizing component. Consequently, histopathological reports should specify the true indicator of poor survival in the lymphadenectomy specimens, which is the size of the largest metastasis in each patient.     

Perlecan domain I-conjugated, hyaluronic acid-based hydrogel particles for enhanced chondrogenic differentiation via BMP-2 release

We have developed a biomimetic growth factor delivery system that effectively stimulates the chondrogenic differentiation of the cultured mesenchymal stem cells via the controlled presentation of bone morphogenetic protein-2 (BMP-2). Hyaluronic acid (HA)-based, microscopic hydrogel particles (HGPs) with inherent nanopores and defined functional groups were synthesized by an inverse emulsion polymerization technique. Recombinantly produced, heparan sulfate (HS)-bearing perlecan domain I (PlnDI) was covalently immobilized to HA HGPs (HGP–P₁) via a flexible poly(ethylene glycol) (PEG) linker through the lysine amines in the core protein of PlnDI employing reductive amination. Compared to HGP without PlnDI, HGP–P₁ exhibited significantly (p < 0.05) higher BMP-2 binding capacity and distinctly different BMP-2 release kinetics. Heparitinase treatment increased the amount of BMP-2 released from HGP–P₁, confirming the HS-dependent BMP-2 binding. While BMP-2 was released from HGPs with a distinct burst release followed by a minimal cumulative release, its release from HGP–P₁ exhibited a minimal burst release followed by linear release kinetics over 15 days. The bioactivity of the hydrogel particles was evaluated using micromass culture of multipotent mesenchymal stem cells (MSCs), and the chondrogenic differentiation was assessed by the production of glycosaminoglycan, aggrecan and collagen type II. Our results revealed that BMP-2 loaded HGP–P₁ stimulates more robust cartilage specific ECM production as compared to BMP-2 loaded HGP, due to the ability of HGP–P₁ to potentiate BMP-2 and modulate its release with a near zero-order release kinetics. The PlnDI-conjugated, HA HGPs provide an improved BMP-2 delivery system for stimulating chondrogenic differentiation in vitro, with potential therapeutic application for cartilage repair and regeneration.     

Cyclooxygenase-2 expression in colorectal cancer liver metastases

Cyclooxygenase-2 (COX-2) is up-regulated in 85-90% of primary human colorectal cancers and is a putative target for the chemopreventative activity of non-steroidal anti-inflammatory drugs. However, COX-2 expression by human colorectal cancer liver metastases has been poorly characterized. We studied a consecutive series of 38 patients who underwent liver resection for metastatic disease, for whom long-term (up to 57 months), prospective follow-up data were available. Semi-quantitative immunohistochemistry for COX-2 was performed on 54 metastases from 35 patients, for whom adequate histological material was available. Diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastases (COX-2 score 1, n=25; score 2, n=29). There was no relationship between metastasis size or differentiation grade and the level of COX-2 protein expression. There was no difference in colorectal cancer-free or overall survival between patients with high (score 2) and low (score 1) COX-2 scores (Kaplan–Meier survival analysis and log rank test, both P=0.97). Multivariate Cox regression analysis identified age, incomplete resection and presence of extra-hepatic disease as independent predictors of disease-free and overall survival following surgery. COX-2 protein was also localized to a subset of stromal fibroblasts and mononuclear cells within metastases as well as hepatocytes from resection specimens. COX-2 protein was expressed by cancer cells in all human colorectal cancer liver metastases which were studied. Investigation of the effect of selective COX-2 inhibition on metastasis growth and metastasis cancer cell proliferation/apoptosis in vivo are warranted.     

Decreased expression of lncRNA loc285194 as an independent prognostic marker in cancer: A systematic review and meta-analysis

BackgroundSeveral studies have indicated that lncRNA loc285194 is aberrantly expressed in many types of cancer. This meta-analysis was performed to elucidate the potential role of lncRNA loc285194 as a prognostic marker in malignant tumors.MethodsAn electronic search of PubMed, Medline, Embase, and Web of Science was performed to identify all eligible papers related to the prognostic impact of lncRNA loc285194 expression in cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were extracted from the included studies to explore the association between lncRNA loc285194 expression and patient overall and disease-free survival (OS & DFS). The odds ratios (ORs) were also calculated to assess the association between lncRNA loc285194 expression and clinicopathological parameters.ResultsA total of 14 eligible articles with 1215 patients were included in this meta-analysis. Meta-results revealed that low expression of lncRNA loc285194 was significantly correlated with poorer overall survival (OS; HR = 2.34; 95% CI, 1.78–3.06; P < 0.001) and disease-free survival (DFS; HR = 2.66; 95% CI, 1.95–3.64; P = 0.001) rates in cancer patients. Low lncRNA loc285194 expression was also found to be significantly associated with lymph node metastasis (LNM; OR = 2.17; 95% CI, 1.23–3.83; P = 0.007), and distant metastasis (DM; OR = 2.49; 95% CI, 1.26–4.91; P = 0.009).ConclusionsThis study demonstrated that decreased level of lncRNA loc285194 was associated with poor clinical outcomes for patients with different types of cancer, supporting a promising potential biomarker for prognosis and metastasis in human cancers.     

Proportion of goblet cell is associated with malignant potential in invasive mucinous adenocarcinoma of the lung

Invasive mucinous adenocarcinoma (IMA) is a newly classified variant of lung adenocarcinoma. The aim of this study was to examine the correlation between the proportion of goblet cells and the clinicopathological characteristics of IMA. Ninety‐nine patients with stage I IMA were included in this study. We estimated prognostic impact of goblet cell proportion. We classified them into two groups: the cases with a high goblet cell proportion (HGP, goblet cell proportion ≥80%) and the cases with a low goblet cell proportion (LGP, goblet cell proportion ≤30%), and compared the expression levels of five cancer progression markers and the number of tumor‐promoting stromal cells between the two groups. Univariate and multivariate analysis revealed that the goblet cell proportion was a prognostic factor for recurrence free survival (P < 0.01) and overall survival (P = 0.01). The expression levels of the cancer stem cell‐related marker, ALDH‐1, and proliferation‐related marker, geminin were significantly higher in the LGP group than in the HGP group. CD204+ tumor‐associated macrophages were significantly more in the LGP stroma than the HGP stroma. Our current study indicated that the proportion of goblet cells was correlated with the malignant potential in surgically resected IMA.     

Metastatic progression of breast cancer: insights from 50 years of autopsies

There remain no clear guidelines for the optimal management of patients with metastatic breast cancer. To better understand its natural history, we undertook a detailed examination of 197 autopsies performed on women who died of breast cancer. We reviewed clinical, treatment and pathological aspects of all cases and, additionally, pathological features and biomarker expression (ER, PgR, HER2, EGFR, p53, Ki67, c‐Kit, CK AE1/AE3) were assessed in detail for the primary tumour and matched metastases for 55 of the cases. Genomes of the primary tumour and multiple metastases were analysed by array‐based comparative genomic hybridization for six cases^##. 945 metastatic deposits were identified, with a median of four/patient. The most common organs involved were lung/pleura (80%), bone (74%), liver (71%) and non‐axillary lymph nodes (55%). Major findings included: (a) patients with CNS metastases were more likely to have bone metastases (p < 0.013); (b) younger age was associated with metastasis to the liver (≤ 49 years; p < 0.001) and to gynaecological organs (≤ 49 years; p = 0.001); (c) surgical excision of the primary tumour was associated with metastasis to the liver (p = 0.002); and (d) ER and PgR showed down‐regulation during progression in a non‐random manner, particularly in lung/pleura (ER; p < 0.001), liver and bone metastases. Genomic analysis revealed DNA copy number variation between the primary tumour and metastases (e.g. amplification of 2q11.2–q12.1 and 10q22.2–q22.3) but little variation between metastases from the same patient. In summary, the association of CNS and bone metastases, liver and gynaecological metastases in young women and the risk of liver metastases following surgery have important implications for the management of patients with breast cancer. Clonal heterogeneity of the primary tumour is important in developing metastatic propensity and the change in tumour phenotype during progression/colonization highlights the importance of sampling metastatic disease for optimal treatment strategies. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Long noncoding RNAs in bladder cancer prognosis: A meta-analysis

BackgroundNumerous studies have demonstrated the involvement of long non-coding RNAs (lncRNAs) in the tumorigenesis of bladder cancer (BC). The aim of this study was to investigate the possible correlations between the specific lncRNAs and the clinical outcomes in bladder cancer patients.MethodsWe systematically searched the PubMed, EMBASE and the Cochrane Library databases for studies published up to October 15, 2018, and retrieved the suitable articles. Pooled odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (95% CIs) were obtained by using fixed-effect or random-effect model.ResultsUp-regulation of lncRNAs predicted unfavorable overall survival (OS) (HR: 2.01, 95%CI: 1.66–2.44, P < 0.001) and recurrence-free survival (RFS) (HR: 2.05, 95%CI: 1.43–2.94, P < 0.001) in BC patients, and the high expression of lncRNAs was significantly associated with distant metastasis (DM) (OR: 8.16, 95%CI: 4.45–14.99, P < 0.001).ConclusionAbnormal expression of relevant lncRNAs are potential novel markers for predicting the clinical outcomes of BC.     

Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple-negative breast cancer

Ohi Y, Umekita Y, Yoshioka T, Souda M, Rai Y, Sagara Y, Sagara Y, Sagara Y & Tanimoto A
(2011) Histopathology 59 , 776–780 Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple‐negative breast cancer Aims: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a reliable marker of breast cancer stem cells, and its clinical significance as a prognostic indicator of breast cancer has been reported by several investigators. However, the clinical significance of ALDH1 expression in triple‐negative (TN) breast cancer, a high‐risk breast cancer lacking the benefit of specific therapy, remains to be solved. Methods and results: We performed immunohistochemical analyses of 106 TN breast cancers, using paraffin‐embedded sections. The basal‐like phenotype was also investigated with the use of basal cytokeratin 5/6 and epidermal growth factor receptor. ALDH1 expression in carcinoma cells was found in 59% of cases and was correlated with high histological grade alone (P < 0.006), whereas ALDH1 expression in stromal cells was found in 49% of cases but was not correlated with any clinicopathological parameter. Patients with ALDH1 expression in carcinoma cells had a shorter relapse‐free survival (RFS) according to the log‐rank test (P = 0.015). According to Cox multivariate analysis, ALDH1 expression in carcinoma cells was an independent prognostic indicator of RFS (P = 0.025). The log‐rank test revealed that stromal expression of ALDH1 had no effect on RFS. Conclusions: ALDH1 expression in carcinoma cells is an independent prognostic factor in TN breast cancer patients.     

Desmoplastic tumour-associated stroma versus neural tissue in central nervous system metastasis: effects of different microenvironments on tumour growth

Chang K‐C, Lu Y‐C, Lin M‐J, Chen H‐Y & Jin Y‐T
(2011) Histopathology 59 , 31–39 Desmoplastic tumour‐associated stroma versus neural tissue in central nervous system metastasis: effects of different microenvironments on tumour growth Aims: Interactions between tumour cells and extracellular matrix (ECM) are critical in the metastatic cascade. We compared effects of desmoplastic stroma versus neural tissue on central nervous system (CNS) metastasis. Methods and results: Using integrins (ECM receptors), ECM (fibronectin, laminin and collagen IV) and CD31 and vascular endothelial growth factor (VEGF) for angiogenesis, this study examined immunohistochemically 69 consecutive cases of CNS metastases. In contrast to low‐level expression in tumour‐embedded neural tissue, ECM [fibronectin (71%), laminin γ‐1 (79%) and collagen IV (92%)] and CD31‐positive microvascular densities (33 versus 4 vessels/field) were significantly richer in desmoplastic tumour stroma, which was present in 90% (53 of 59) of carcinomas, 100% (five of five) of malignant melanomas and 100% (two of two) of sarcomas. Collagen IV expression in tumour stroma was correlated with the expression of fibronectin (P = 0.013) and laminin (P = 0.034) and with infiltrative tumour edges (P = 0.005); fibronectin‐positive tumour stroma was correlated with a higher microvascular density (P = 0.015). In addition, tumour cells expressed integrins (～75%) and laminin (84%) more frequently than VEGF (23%), and tumour expression of laminin was correlated with the presence of desmoplastic stroma (P = 0.006). Interestingly, laminin‐positive tumour stroma was a worse prognosticator (P = 0.072). Conclusions: ECM‐ and vascular‐rich stroma is important in tumour growth, which underlies therapeutic strategies targeting tumour‐associated stroma.