Molecular diagnosis of prostate cancer

The diagnosis, staging, and management of prostate cancer as we know it today is greatly dependent on our ability to measure serum prostate-specific antigen (PSA) concentration. Nevertheless, because serum PSA concentration, particularly when less than 10 ng/mL, reflects the presence of benign prostatic hyperplasia more often than cancer, there is a clear need for more specific prostate cancer markers. The most promising new markers for prostate cancer are the various molecular forms of free PSA. Mass spectrometry also is emerging as a potential tool in prostate cancer screening. Because it is unlikely that any one marker will have 100% sensitivity and specificity, as new serum markers are tested, nomograms that incorporate multiple independently predictive parameters for the detection of prostate cancer will become indispensable in our efforts to improve prostate cancer screening.     

Putative tissue markers in prostate cancer*

A variety of putative prostate cancer markers have been described in human serum, urine, seminal fluid, and histological specimens. These markers exhibit varying capacities to detect prostate cancer and to predict disease course. In order to be considered markers for diagnosis or prognosis of disease course, and to be brought forward for large-scale clinical evaluation, they should fulfill several criteria. Firstly, there should be a biological or therapeutic rationale for choosing the marker, or at least a consistent association with disease presence, disease characteristics such as stage, or disease aggressiveness. Secondly, there should be an assessment of the strength of marker association with disease outcome. Thirdly, the marker should be assessed as an independent predictor in a multivariate analysis.     

Molecular prognostic markers in pancreatic cancer

Pancreatic cancer has a very poor prognosis and is a common cause of cancer death in the Western world. Certain genetic alterations may be important in the prognosis of pancreatic cancer. Activation mutations in the K‐ras oncogene occur in around 90% of pancreatic cancers, and the overexpression of growth factors epidermal growth factor (EGF), transforming growth factor (TGF)α, TGFβs 1–3, acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and growth factor receptors c‐erbB‐2 and ?3 and TGFRβs 1–3 is common. High mutation levels of cell cycle control genes such asp53,p16,p21,SMAD4, and cyclin D1 are found, and there is abnormal expression of apoptotic genes, such asbcl‐2,bcl‐XL, andbax. The expression of several of these growth factors and their receptors has been found to be associated with poorly differentiated tumors of an advanced stage and decreased survival. However, the inactivation and loss of expression ofp16,p53, andp21, and the expression of several apoptotic genes, such asbax andbcl‐2, have not been found to be of any prognostic significance. The expression of wild typep53, however, may predict responsiveness to chemotherapy. TGFβ1 expression has been shown to be associated with longer survival in patients with pancreatic cancer. Two studies (including our own) have foundbcl‐XL expression to be significantly associated with poor survival. These and newer molecular markers may prove to be important in the choice of future therapies for pancreatic cancer.     

前列腺特异性抗原及骨标志物检测对前列腺癌骨转移患者诊断的意义

目的 探讨前列腺特异性抗原(PSA)、骨形成标志物碱性磷酸酶(ALP)与骨吸收标志物抗酒石酸酸性磷酸酶5b(TRACP5b)、Ⅰ型胶原吡啶交联终肽(ICTP)在前列腺癌骨转移诊断的意义. 方法 通过测定57例老年前列腺癌患者(年龄61～90岁)PSA、TRACP5b、ALP、ICTP血清浓度,分成骨转移(27例)与非骨转移(30例)两组,以转移灶在5个及以上者划分为进展性(18例)和局限性骨转移(39例).采用受试者工作特征曲线( ROC)评估各标志物诊断前列腺癌骨转移的价值.结果 PSA、TRACP5b、ALP、ICTP血清浓度在前列腺癌骨转移组均高于非骨转移组(P＜0.05);与局限性骨转移组比较,PSA、TRACP5b、ALP、ICTP、Gleason评分在进展性骨转移组中均有明显升高(P＜0.05);PSA、TRACP5b、ALP、ICTP诊断前列腺癌骨转移的曲线下面积(AUC)分别为0.796、0.657、0.762、0.743,最高诊断价值的是PSA,ALP、ICTP与之相当,TRACP5b次之,其敏感性分别为66.7％、59.3％、37.0％、59.3％,特异性则为90.0％、96.7％、80.0％、76.7％;PSA、ALP、ICTP与Gleason评分是预测前列腺癌骨转移的独立性因素,总符合率为84.2％. 结论 PSA、TRACP5b、ALP、ICTP诊断前列腺癌骨转移的价值相当,联合检测并动态观察可能有利于前列腺癌骨转移的早期诊断.     

前列腺癌相关生物标志物的研究进展

前列腺癌作为男性最为常见的癌症之一,严重威胁着男性的健康安全。前列腺癌在预测、诊断、预后方面都面临着诸多挑战。虽然用于指导前列腺癌的各种生物标志物具有一定的临床意义,但在单独使用时仍然显现出各自的局限性。精确诊断、防止过度活检、生物标志物联合诊断体系构建等仍然是当今前列腺癌检测的研究热点。本文分析了前列腺癌在检测中所面临的问题,并就临床上常用的前列腺癌生物标志物及其相关检测体系的研究进展进行综述。     

Prognostic value of serum markers for prostate cancer

The incidence of prostate cancer has increased dramatically during the last 10-15 years and it is now the commonest cancer in males in developed countries. The increase is mainly caused by the increasing use of opportunistic screening or case-finding based on the use of prostate-specific antigen (PSA) testing in serum. With this approach, prostate cancer is detected 5-10 years before giving rise to symptoms and on average 17 years before causing the death of the patient. While this has led to detection of prostate cancer at a potentially curable stage, it has also led to substantial overdiagnosis, i.e. detection of cancers that would not surface clinically in the absence of screening. A major challenge is thus to identify the cases that need to be treated while avoiding diagnosing patients who will not benefit from being diagnosed and who will only suffer from the stigma of being a cancer patient. It would be useful to have prognostic markers that could predict which patients need to be diagnosed and which do not. Ideally, it should be possible to measure these markers using non-invasive techniques, i.e. by means of serum or urine tests. As it is very useful for both early diagnosis and monitoring of prostate cancer, PSA is considered the most valuable marker available for any tumor. Although the prognostic value of PSA is limited, measurement of the proportion of free PSA has improved the identification of patients with aggressive disease. Furthermore, the rate of increase in serum PSA reflects tumor growth rate and prognosis but, due to substantial physiological variation in serum PSA, reliable estimation of the rate of PSA increase requires follow-up for at least 2 years. Algorithms based on the combined use of free and total PSA and prostate volume in logistic regression and neural networks can improve the diagnostic accuracy for prostate cancer, and assays for minor subfractions of PSA and other new markers may provide additional prognostic information. Markers of neuroendocrine differentiation are useful for the monitoring of androgen-independent disease and various bone markers are useful in patients with metastatic disease.     

肝癌早期诊断分子标志物的研究进展

腹部超声、CT、数字减影血管造影的检查，虽能发现肝癌(HCC)，但对监测单个癌细胞较难。肝癌诊断特异蛋白及相关基因分析，有助于肝癌诊断、疗效观察、术后随访、复发或转移监测。     

Molecular basis of androgen blockade in prostate cancer

The molecular basis for antiandrogen therapy is reviewed. This article covers the structure and function of the androgen receptor, including the relationship between mutations in the receptor and the acquisition of androgen independent growth. Implications for anti-androgen therapy are addressed.     

Molecular and clinical markers of pancreas cancer

Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those with hereditary pancreatitis and genetic syndromes which predispose to cancer. Ongoing work to identify early markers of pancreas cancer consists of high throughput discovery methods including gene arrays and proteomics as well as hypothesis driven methods. While several promising candidates have been identified none has yet been convincingly proven to be better than CA 19-9. New methods including endoscopic ultrasound are improving detection of pancreas cancer and are being used to acquire tissue for biomarker discovery.     

Molecular diagnosis of pancreatic cancer

Pancreatic ductal adenocarcinoma is a result of accumulated genetic alterations, including oncogenes such as K-ras, tumor-suppressor genes such as p53, p16 and DPC4 and genome-maintenance genes such as BRCA2, microsatellite instability and telomerase. Recent findings which characterize the molecular genetic profile of the pancreatic cancer have reshaped the nomenclature describing histological progression in pancreatic ductal tumorigenesis. K-ras mutations frequently occur early, whereas changes in the expression and genetic integrity of the p16 gene appear in intermediate lesions, and the inactivation of the p53, DPC4 genes and activation of telomerase occur late in the neoplastic progression. So far K-ras and telomerase activity have been used as molecular markers for the diagnosis of pancreatic carcinoma, whereas p53 and p16 may be a prognostic indicator of pancreatic cancer. Additional tumor-suppressor genes and the related signaling pathway such as ALK-5 are likely to be defined. In addition to the human genome project, these new advances hopefully will accelerate the development of diagnostic and screening techniques for this grave condition.     

肺癌相关标志物在肺癌早期诊断中的应用

<正>肺癌是目前发病率和病死率最高的恶性肿瘤。尽管在其治疗领域取得了一系列进展,然而肺癌患者的5年生存率仍未显著地提高。早期诊断率低,丧失最佳治疗时机,是导致肺癌疗效差及病死率高的主要原因。因此,如何提高肺癌的早期诊断率是临床医师和相关基础研究者努力的重要     

多肿瘤标志物蛋白芯片诊断前列腺癌

目的:探讨多肿瘤标志物蛋白质芯片检测系统在筛查高危人群前列腺癌发生中的作用.方法:采用多肿瘤标志物蛋白质芯片检测系统检测泌尿外科189例前列腺疾病患者血清中12种肿瘤标志物CA19-9、CA242、CEA、AFP、NSE、Ferritin、β-HCG、fPSA、tPSA、CA125、CA15-3、HGH的含量.结果:189例前列腺疾病患者血清中,fPSA和tPSA升高超过正常者分别为15.3%(29/189)和39.7%(75/189),病理诊断前列腺癌共13例,fPSA和tPSA联合诊断前列腺癌的敏感性和特异性分别为100%(13/13)和64.8%(114/176).结论:多肿瘤标志物蛋白质芯片检测系统是进行快速和规模性筛查前列腺癌的可行和有效手段.     

Update on the diagnosis and management of prostate cancer

Early detection of prostate adenocarcinoma (prostate cancer) through screening tests such as a serum prostate-specific antigen (PSA) test and a digital rectal examination (DRE) enables primary care physicians and urologists to offer patients a broader choice of treatments that are also more likely to provide a cure. Whether men are being over treated or over diagnosed through the widespread use of screening tests remains controversial. This review aims to provide general practitioners with a better understanding of different prostate cancer tests that can be performed and to help them decide which patients should be referred to a urologist for an ultrasound-guided biopsy.     

血清肿瘤标记物在肺癌诊断中的意义

目的　明确癌胚抗原 (CEA)、大分子糖蛋白抗原 (CA1 2 5)、细胞角蛋白 (Cyfra2 1 - 1 )在肺癌诊断中的意义。方法　收集血清标本 74份 ,其中肺部良性病变组 2 8例 ,肺腺癌组 19例 ,肺鳞癌组 16例 ,小细胞肺癌组 11例。CEA、CA1 2 5、Cyfra2 1 - 1 均用电化学发光分析技术检测 ,结果以均值±标准差和特异度及灵敏度两种方式评价。结果　 CEA的水平 ,良性病变组在正常参考范围内 ;腺癌、鳞癌、小细胞癌组均明显高于正常值上限 ,而各肺癌组间比较无显著差异 ,各肺癌组与肺部良性病变相比 ,均有显著性差异 (P<0 .0 0 1)。 CA1 2 5各组病变中均高于正常参考值 ,各组比较 ,只有肺腺癌组与良性病变组有显著性差异。 Cyfra2 1 - 1 在肺腺癌组、鳞癌组明显高于正常值 ,统计学上有显著性差异 ,良性病变组和小细胞癌组其值均在正常参考值范围内 ,但两组之间有显著性差异。 CEA的特异性高达 82 .14 % ,灵敏度为 5 8.6 9% ;CA1 2 5的灵敏度较高 ,但特异性很低 ,仅 4 2 % ;Cyfra2 1 - 1 的特异性近 90 % ,但灵敏度仅 4 5 %。对不同病理类型各肿瘤标记物的灵敏度亦不同 ,CEA、CA1 2 5在各型间无差别 ;Cyfra2 1 - 1 在非小细胞肺癌和小细胞肺癌间差别有统计学意义。结论　 CEA在肺部恶性病变中的特异性较高 ,灵敏度亦可     

经直肠超声前列腺癌声像特征及前列腺内腺PSA密度在前列腺癌诊断中的作用

目的通过经直肠超声分析前列腺癌声像特征并测量前列腺内腺、外腺与总体积，参考PSA探讨前列腺内腺PSA密度(IPSAD)在前列腺癌与前列腺增生鉴别诊断中的意义。方法回顾分析经直肠超声前列腺癌声像特征及经超声引导下6点活检病理诊断的49例前列腺癌、96例前列腺增生的临床资料。结果(1)前列腺癌声像特征以低回声为主，晚期可见被膜浸润及不规则。(2)前列腺内腺体积增生与癌有显著性差别。(3)PSA、PSA密度(PSAD)、IPSAD在增生与前列腺癌中的比较，均有显著性差异。(4)IPSAD在前列腺癌诊断的特异度为75．5％，敏感度为93．3％，优于PSAD。结论前列腺癌声像特征及IPSAD是鉴别前列腺癌与增生的重要指标。     

血清fPSA对老年前列腺癌诊断的应用价值

目的　探讨血清游离前列腺特异抗原 (f PSA)及游离 PSA/总前列腺特异抗原 (t PSA)比值对前列腺癌的诊断价值。方法　用酶联免疫方法检测 1 30例前列腺癌 (PCa)、76例前列腺增生 (BPH)以及 42例正常对照组的血清 f PSA、t PSA,并计算 f PSA/ t PSA比值 ,评价其对前列腺癌的诊断价值。结果　以 f PSA/ t PSA比值为 0 .1 5为评判上限时 ,前列腺癌组明显低于前列腺增生组及正常对照组 (P<0 .0 1 ) ,认为 f PSA及 f PSA/t PSA比值可有效区分 PCa和 BPH(P<0 .0 0 5) ,其诊断敏感性为 91 .6% ,特异性为 88.1 % ,准确性为 87.8% ;尤其是当 PSA值界定在 4～ 1 0μg/ L灰区范围内效果更明显优于常规的 t PSA和 f PSA单独测定结果。结论　 f PSA和 f PSA/ t PSA比值的应用 ,使血清 PSA测定更具临床意义 ,提高了前列腺癌的早期诊断