The role of novel biomarker HE4 in endometrial cancer: a case control prospective study

The aim of the study was to explore the clinical value of serum human epididymis secretory protein E4 (HE4) and CA125 in endometrial carcinoma. From January 2010 to April 2012, serum specimens were collected from consecutive cases of endometrial carcinoma and from cases of uterus benign disease (control group). The CA125 normal value is considered less than 35 U/mL. Two HE4 cutoff are considered: less than 70 pmol/L and less than 150 pmol/L. The specificity analysis was performed using the Mann–Whitney test for the CA125 and HE4 series. The level of statistical significance is set at p?<?0.05. The sensitivity of CA125 in detecting endometrial cancer is 19.8 %, whereas the sensitivity of HE4 is 59.4 and 35.6 % for 70 and 150 pmol/L cutoff, respectively. Thus the specificity of HE4 is 100 % (positive predictive value?=?100 %, negative predictive value?=?71.52 and 61.31 % considering the two HE4 cutoff, respectively), whereas the CA125 specificity is 62.14 % (positive predictive value?=?33.9 %, negative predictive value?=?44.14 %) in detection of endometrial cancer. Combining CA125 and HE4, the sensitivity to detect endometrial cancer is 60.4 and 34.6 %, at HE4 cutoff of 70 and 150 pmol/L, respectively, with a specificity of 100 %. HE4 may be a new tool for preoperative evaluation and postoperative surveillance of endometrial cancer patients, with a positive predictive value?=?100 %. HE4 at cutoff of 70 pmol/L yields the best sensitivity and specificity.     

Association of Serum HE4 with Primary Tumor Diameter and Depth of Myometrial Invasion in Endometrial Cancer Patients at Rajavithi Hospital

Background: Although there are no biomarkers that are routinely used in endometrial cancer (EC) management, many studies have found that serum human epididymis protein 4 (HE4) is superior to cancer antigen 125 (CA125) in the detection of EC. The correlation of HE4 with two prognostic factors for EC, primary tumor diameter (PTD) and depth of myometrial invasion (DMI) may be useful in identifying EC patients at high risk of lymphatic dissemination. Objective: To evaluate the correlation of serum HE4 with PTD and DMI in patients with EC. Materials and Methods: A cross-sectional study was conducted on 70 EC patients who were scheduled for elective surgery at Rajavithi Hospital between 1st September 2013 and 30th May 2014. Preoperative serum levels of HE4 and CA125 were investigated, and then gross measurement of PTD was taken and postoperative pathologic slides were reviewed for DMI including histologic types, grading and staging. Results: Preoperative serum HE4 levels were strongly correlated with PTD (r=0.65, p<0.001) and moderately correlated with DMI (r=0.46, p<0.001). Moreover, serum HE4 levels were significantly elevated in EC patients with PTD >2 cm (p<0.001) and DMI > 50% (p=0.004). The performance of serum HE4 in identifying EC patients at low risk and high risk of lymph node metastasis was significantly better than that of CA125 (AUC 0.88 vs. 0.65, p=0.003). At an optimal cut-off value of 70 pM/L, serum HE4 had a sensitivity of 83.3% and a specificity of 80.0%. Conclusions: In EC patients, preoperative serum HE4 is significantly correlated with PTD and DMI. Serum HE4 levels could be useful in identifying endometrial cancer patients at high risk of lymphatic spread who would benefit from systemic lymphadenectomy at the cut-off value of 70 pM/L.     

Serum Human Epididymis Protein-4 (HE4) - A novel Approach to Differentiate Malignant Frombenign Breast Tumors

Background: The lack of sensitivity and specificity of existing diagnostic markers like Carbohydrate Antigen 15-3(CA15-3) and Carcinoembryonic antigen (CEA) in breast cancer stimulates the search for new biomarkers to improve diagnostic sensitivity especially in differentiating benign and malignant breast tumors. Expression of Human epididymal protein 4 (HE4) has been demonstrated in ductal carcinoma of the breast tissue. So we tried to evaluate serum HE4 levels as diagnostic marker in breast cancer patients and to comparatively assess serum HE4, CEA and CA15-3 in breast tumor patients both benign and malignant. Methods: Total 90 female subjects were included in the study. We selected 30 breast cancer cases (Malignant group) and 30 benign breast lump cases (Benign group) based on histopathology report. And other 30 were age matched apparently healthy controls (Control group). HE4, CEA and CA15-3 were analysed in serum samples of all subjects by Electrochemiluminiscence immunoassay method. Results: A significant difference in the median (IQR) of HE4 (pmol/l) was identified among malignant, benign and control groups {62.4(52.6-73.7) vs 49.3(39.8-57.4) vs 52.3(50.6-63.3) P=0.0009} respectively. The cutoff value for prediction of breast cancer was determined at >54.5 pmol/l for HE4, with a sensitivity of 73.3%, specificity of 65.3%, whereas cutoff value of CA 15-3 was >21.24 (U/ml) with a sensitivity of 56.7%, specificity of 74.5%. For CEA at cutoff value >0.99 (ng/ml) the sensitivity and specificity were 96.7 % and 62.7% respectively. AUC for HE4, CA15-3 and CEA were 0.725, 0.644 and 0.857 respectively. Conclusion: Our study demonstrated that serum levels of HE4 were significantly higher in malignant group compared to benign and control groups. There is no significant difference between HE4 levels between benign and control groups. These results indicate that HE4 appears as a useful and highly specific biomarker for breast cancer, which can differentiate between malignant and benign tumors.     

CA125、HE4、AngII联合检测诊断子宫内膜癌

目的:探讨糖链抗原125（CA125）、附睾蛋白4（HE4）和血管紧张素II（AngII）单检以及联合检测在子宫内膜癌（endometrial cancer,EC）诊断的应用价值。方法:搜集2013年1月至2014年11月在中国医科大学附属盛京医院就诊的130例EC患者作为实验组以及46例健康女性作为对照组。检测其CA125表达水平。同时应用酶联免疫试验（ELISA）技术对血清中HE4、AngII表达水平进行检测,分析三种肿瘤标记物单独检测时各自的灵敏度、特异度的优、缺势,及联合检测时灵敏度和特异度否有所提升。结果:实验组血清中CA125、HE4、AngII的表达水平分别是34.33±14.45、78.19±32.31、13.82±5.42,而对照组中其表达水平分别为13.30±9.22、45.61±15.70、7.70±3.58,EC组血清CA125、HE4、AngII明显高于对照组,分别比较,差异均有统计学意义（P<0.05）。CA125、HE4、AngII在EC的I-II期组阳性率分别为37.27%、47.27%、7.27%;III-IV期组阳性率分别为60%、70%、35%,对比三者各自的阳性率发现,在早期三者的诊断率均较晚期低;将其按年龄分为＜60岁、 ≥60岁,CA125、HE4、AngII三者在＜60岁组的阳性率分别为46.15%、32.69%、9.61%;在≥60岁组的阳性率分别为37.18%、70.78%、24.37%,对比发现,CA125在年龄方面无明显区别,而HE4、AngII在年龄方面却有显著差异;CA125、HE4、AngII三者检测的灵敏度分别为49.23%、52.31%、46.15%,三者联检的灵敏度为86.15%;CA125、HE4、AngII三者检测的特异度分别为89.30%、91.65%、85.65%,三者联检的特异度为73.60%,联合检测可以提高诊断的灵敏度,但特异度却相对降低。结论:单项肿瘤标记物在子宫内膜癌中的诊断价值具有一定的局限性,但3项联合检测可有效提高子宫内膜癌的诊断性能及早期检出率,是检测子宫内膜癌的较为理想的标志物组合。     

术前血清CA125、HE4和中性粒细胞与淋巴细胞比值联合检测在子宫内膜癌诊断中的作用

目的:探讨血清糖类抗原125（carbohydrate antigen 125,CA125）、人附睾蛋白4（human epididymis protein 4,HE4）、中性粒细胞与淋巴细胞比值（neutrophil-lymphocyte ratio,NLR）联合检测在子宫内膜癌诊断中的作用。方法:选取42例子宫内膜癌患者、50例子宫内膜良性疾病患者和50例健康体检人群。采用SYSMEX XN550全自动血液分析仪计数术前外周血中性粒细胞和淋巴细胞,计算NLR;采用Maglumi4000全自动化学发光仪检测术前血清CA125、HE4水平。采用ROC曲线分析CA125、HE4、NLR和三者联合指标在诊断子宫内膜癌中的作用。结果:外周血NLR在健康组、良性组和子宫内膜癌组中逐渐增高,且差异有统计学意义（P<0.05）;子宫内膜癌组HE4表达量显著高于良性组与健康组（P<0.05）,而良性组与健康组之间差异无统计学意义（P>0.05）;CA125表达量在三组中差异无统计学意义（P>0.05）。CA125、HE4、NLR及三者联合标记物的AUC分别为0.530、0.733、0.795、0.823,当分别取它们的临界值时,特异性分别为70.8%、85.1%、61.7%、83.0%,敏感性分别为40.0%、63.3%、86.7%、73.3%。单项指标NLR的敏感性最高,HE4的特异性最高,联合指标的特异性和敏感性都很高。结论:术前血清CA125、HE4和NLR联合检测具有较高的特异性和敏感性,联合检测可以互为补充,提高子宫内膜癌的诊断准确率,对子宫内膜癌的诊断具有指导意义。     

子宫内膜癌患者血清人附睾分泌蛋白4（HE4）、糖类抗原125（CA125） 的检测及其临床价值

目的:探讨子宫内膜癌患者血清人附睾分泌蛋白4（human epididymal secretory protein 4,HE4）、糖类抗原125（carbohydrate antigen 125,CA125）水平变化及其临床价值。方法:选取我院126例子宫内膜癌患者作为恶性组,同期81例子宫内膜增生患者作为良性组,114例体检健康女性作为对照组,观察各组HE4、CA125变化情况,用ROC曲线对HE4、CA125子宫内膜癌最佳诊断切点实施分析,评价两种指标单独检验与联合测定诊断子宫内膜癌的准确性及临床价值。结果:HE4诊断子宫内膜癌相比CA125具有明显优势（P＜0.05）;各组患者HE4、CA125水平对比,差异具有统计学意义（P＜0.05）;恶性组HE4、CA125水平显著高于良性组及对照组（P＜0.05）。HE4诊断子宫内膜癌灵敏度、特异度、符合率等均高于CA125,单独检验差异不具有统计学意义（P>0.05）。结论:联合测定HE4、CA125这两种指标诊断子宫内膜癌具有较高灵敏度与特异度,HE4诊断子宫内膜癌效果优于CA125,HE4与CA125联合检验具有互补作用,可以避免单独检验发生的误诊漏诊,提高临床诊断子宫内膜癌准确率。     

Use of serum tumor markers in the differential diagnosis between ovarian and colorectal adenocarcinomas.

In the search for a method to facilitate the preoperative discrimination of ovarian carcinomas from colorectal carcinomas serum levels of 6 tumor markers were measured in 47 patients presenting with ovarian cancer and compared to levels found in 24 female patients with advanced, untreated colorectal cancer. The markers studied were CA 125, CA 15.3, CA 19.9, CEA and two recently developed mucin markers, CA M29 and CA M26. Levels of CA 125, CA 15.3, CEA and CA M29 showed significant differences between both groups. In predicting ovarian cancer, sensitivity was highest for CA 125 at 94% (35 U/ml cutoff level). However, the specificity of CA 125 was at 71% low. Specificity increased significantly by using a combination of a CA 125-positive score (greater than 35 U/ml) and a simultaneous negative CEA score (less than or equal to 5 ng/ml) (specificity 100%, sensitivity 81%). A CA 125/CEA serum ratio greater than 25 resulted in the highest discriminative power with a specificity of 100% and a sensitivity of 91% resulting in an overall test accuracy of 94%. It is concluded that the serum tumor markers used, especially a combination of CA 125 and CEA, are helpful in the preoperative differential diagnosis between adenocarcinomas of ovarian and colorectal origin.     

血清miR-15b诊断子宫内膜癌及预判淋巴结转移的价值分析

[目的]探讨血清miR-15b用于诊断子宫内膜腺癌的价值及其对淋巴结转移的预判能力。[方法]选取21例我院收治并诊断为子宫内膜腺癌及13例无生殖系统疾病的健康女性,采用酶联吸附法检测血清CA125、HE4水平,应用实时荧光定量技术对血清中miR-15b的水平进行相对定量。利用相关和回归分析对miR-15b指标与CA125、HE4做关联探讨;对子宫内膜腺癌患者淋巴结转移情况与miR-15b变量值进行ROC分析,寻找最佳的截断值。[结果]子宫内膜腺癌患者的血清CA125、HE4和miR-15b含量均高于对照组,差异有统计学意义。CA125与HE4、HE4与miR-15b之间存在线性正相关关系。CA125在FIGO各期中比较无差异,HE4和miR-15b在FIGO的各期均存在差异。当血清miR-15b水平相对于正常健康人群高出3倍,此时诊断淋巴转移的敏感度为90.91%,特异性为60%。[结论]血清HE4与miR-15b可联合诊断子宫内膜腺癌,且miR-15b在子宫内膜腺癌的FIGO病理分期中存在差异,在判断肿瘤淋巴结转移方面有较高的价值。     

糖类抗原125、糖类抗原15-3、糖类抗原19-9和人附睾蛋白4单独及联合检测对卵巢癌的诊断价值

目的研究糖类抗原125(CA125)、CA15-3、CA19-9和人附睾蛋白4(HE4)单独及联合检测对卵巢癌的诊断价值,探讨最优的联合诊断方案。方法选取90例卵巢癌患者、90例良性卵巢疾病患者及90同期健康体检者,分别作为肿瘤组、良性组和健康组。比较3组受试者血清CA125、CA15-3、CA19-9和HE4水平及阳性率,比较上述四种肿瘤标志物单独及联合检测对卵巢癌的诊断灵敏度、特异度及准确度。结果肿瘤组患者CA125、CA15-3、CA19-9和HE4水平及阳性率均高于良性组患者和健康组受试者,良性组患者血清CA125、CA15-3和CA19-9水平均高于健康组受试者,良性组患者血清CA125、CA15-3、CA19-9和HE4阳性率均高于健康组受试者,差异均有统计学意义(P﹤0.05)。CA125+CA15-3+HE4、CA125+CA15-3+CA19-9+HE4诊断卵巢癌灵敏度最高,均为91.11%。HE4单独诊断卵巢癌的特异度最高,为94.44%。CA125+CA15-3+HE4诊断卵巢癌的准确度最高,为85.93%。结论CA125+CA15-3+HE4三项联合检测可提高卵巢癌诊断效率,对临床诊断卵巢癌有参考价值。     

Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses

Background: Ovarian cancer remains a major worldwide health care issue due to the lack of satisfactory diagnostic methods for early detection of the disease. Prior studies on the role of serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in detecting ovarian cancer presented conflicting results. New tools to improve the accuracy of identifying malignancy are urgently needed. We here aimed to evaluate the diagnostic utility of tissue CA125 and HE4 gene expression in comparison to serum CA125 and HE4 in discriminating benign from malignant pelvic masses. Materials and Methods: One-hundred Egyptian women were enrolled in this study, including 60 epithelial ovarian cancer (EOC) patients and 20 benign ovarian tumor patients, as well as 20 apparently healthy women. Preoperative serum levels of CA125 and HE4 were measured by immunoassays. Tissue expression levels of genes encoding CA125 and HE4 were determined by quantitative real time polymerase chain reaction (qRT-PCR). The diagnostic performance of CA125 and HE4, measured either as mRNA or protein levels, was evaluated by receiver operating characteristic (ROC) curves. Results: The serum CA125+HE4 combination and serum HE4, with area under the curve (AUC) values of 0.935 and 0.932, respectively, performed significantly better than serum CA125 (AUC=0.592; P<0.001). Tissue CA125 and HE4 (AUC=1) performed significantly better than serum CA125 (P<0.001), serum HE4 (P=0.016) and the serum CA125+HE4 combination (P=0.018). Conclusions: Measurement of tissue CA125 and HE4 gene expression not only improves discriminatory performance, but also broadens the range of differential diagnostic possibilities in distinguishing EOC from benign ovarian tumors.     

Diagnostic accuracy of CA125 and HE4 in ovarian carcinoma patients and the effect of confounders on their serum levels

ObjectivesTo evaluate the diagnostic accuracy of serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in the prediction of malignant ovarian masses then to analyze the effect of personal criteria and medical diseases on this accuracy.Study DesignThis prospective study was performed in Zagazig University Hospital. The eligibility criteria for inclusion were; consecutive women, at any age ≥18 years, with established diagnosis of ovarian mass based on symptoms, signs, and imaging techniques. All patients underwent personal and medical history taking, preoperative serum CA125 and HE4 (cutoff 35 IU/mL and 150 pmol/L, respectively) assessment then postoperative histopathologic examination of lesions as a reference standard.ResultsAmong the included 140 patients, 62 were confirmed to have ovarian malignancy and 78 had benign lesions. Serum CA125 ≥35 IU/mL was associated with ovarian malignancy at sensitivity 91.9%, specificity 53.8%, and accuracy 70.7%. Raising its cutoff to 67.5 IU/mL decreased the sensitivity 83.9%, increased the specificity 80.7% with accuracy 82.1%. The combination of HE4 and CA125 showed sensitivity 75.8%, specificity 93.5%, and accuracy 85.7%. Women suffering from both diabetes mellitus and hypertension showed a significant decrease in CA125 concentration P = 0.02 with false negative results in (5/11) of them, making its sensitivity 54.5% in this condition.ConclusionsThe performance of CA125 in cancer ovary prediction can be improved by increasing its cutoff or by combining CA125 with HE4. Diabetes mellitus and hypertension can influence CA125 performance while HE4 is independent on these factors. This can be an additional value of the introduction of HE4 in cancer ovary prediction protocols.     

Evaluating the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer

We evaluated the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer (SCLC). Serum HE4 level was measured in serum samples from 30 healthy controls and 49 patients with SCLC using enzyme-linked immunosorbent assay. HE4 expression in tumor tissues was analyzed by immunohistochemical staining. The results show that serum HE4 level is significantly higher in SCLC patients than those in healthy controls, which is also the case in tumor tissues where strong intracytoplasmic staining is demonstrable. Using the optimal cutoff value of 84.19 pmol/l, serum HE4 level distinguishes SCLC patients from healthy controls with a sensitivity of 69.4 %, a specificity of 93.3 %, and the area under the receiver operating characteristic curve (AUC) of 0.85. Compared to other well-known tumor markers used in lung cancer diagnosis, HE4 shows the highest sensitivity (69.4 %, 34 of 49) and accuracy (78.5 %, 62 of 79) in diagnosing SCLC, and combinations with other tumor markers further increase the sensitivity and accuracy. These findings suggest that HE4 levels are greatly elevated in sera and tumor tissues of patients with SCLC and serum HE4 is a potential diagnostic marker for patients with SCLC.     

人附睾分泌蛋白4检测对子宫内膜癌的诊断及预后的意义

目的 比较血清人附睾分泌蛋白4(HE4)与CA125检测对早期及不同病理亚型子宫内膜癌的诊断价值.方法分别采用酶联免疫吸附试验及化学发光法对子宫内膜癌组(62例)及正常子宫内膜组(66例)血清HE4及CA125水平进行检测,评估两种诊断方法对子宫内膜癌的诊断价值.结果 (1)与正常组比较,HE4在子宫内膜癌患者血清中...     

Diagnostic utility of CYFRA 21-1, carcinoembryonic antigen, CA 125, neuron specific enolase, and squamous cell antigen level determinations in the serum and pleural fluid of patients with pleural effusions.

BACKGROUND: To the authors' knowledge the role of tumor marker determination in the differential diagnosis of pleural effusions has not been established definitively. The current article reports the results of a study of CYFRA 21-1, carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), squamous cell antigen (SCC), and neuron specific enolase (NSE) in the serum and pleural fluid of patients with pleural effusions of diverse etiologies. METHODS: One hundred forty-six patients with pleural effusions (43 malignant, 47 tuberculous, 32 miscellaneous benign, and 24 paramalignant) were studied prospectively. Levels of CYFRA 21-1, CA 125, CEA, NSE, and SCC were measured by radioimmunoassay in the pleural fluid in all patients and in the serum in 118 patients. RESULTS: There were no significant differences between the serum and pleural fluid levels of tumor markers with the exception of CA 125, which was higher in the pleural fluid. With maximum specificity, the highest sensitivity in the diagnosis of pleural malignancy was obtained with a combination of CYFRA 21-1 (with a cutoff value of 150 U/L), CEA (with a cutoff value of 40 ng/mL), and CA 125 (with a cutoff value of 1000 ng/mL) in pleural fluid. NSE and SCC added no diagnostic value. The simultaneous use of tumor markers and cytology in pleural fluid increased the sensitivity from 55.8% to 81%. CONCLUSIONS: These findings suggest that a combination of CYFRA 21-1, CEA, and CA 125 in the pleural fluid can be a useful addition to pleural cytology in the diagnosis of malignant pleural effusion.     

Serum HE4 superior to CA125 in predicting poorer surgical outcome of epithelial ovarian cancer

Epithelial ovarian cancer (EOC) remains the deadliest form of gynecological cancers. Optimal tumor debulking, no matter the primary or the interval, is the most important prognostic factor for EOC, so there is an urgent demand for biomarkers to predict surgical outcome. The aim of this study was to investigate whether serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) could predict surgical outcome of EOC. The levels of preoperative serum HE4 and CA125 were determined by electrochemiluminescence (ECLIA) in 82 EOC patients, comprising 39 subjected to primary debulking surgery (PDS) and 43 with extensive stage III or IV disease to neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS). Among 39 patients subjected to primary debulking surgery, HE4 was superior to CA125 in predicting surgical outcome (area under curve [AUC] 0.758 vs. 0.633). At a cutoff of 353.22 pmol/L, HE4 reached 77.4 % in sensitivity and 75 % in specificity. The prediction of surgical outcome of interval debulking surgery based on preoperative HE4 and CA125 values was performed in 43 patients who received NACT-IDS. The difference of AUC between HE4 and CA125 (0.793 vs. 0.663) indicating that HE4 was the better biomarker to predict surgical outcome of IDS. A pre-IDS HE4 value of 154.3 pmol/L is the optimal cutoff to identify patients who would not benefit from IDS with a sensitivity of 92.9 % and a specificity of 69 %. The change (>70 %) of HE4 before and after neoadjuvant chemotherapy could predict optimal interval debulking surgery. Serum HE4 was superior to CA125 in predicting surgical outcome of primary debulking surgery and interval debulking surgery. The change (absolute value or percentage) of HE4 in neoadjuvant chemotherapy could predict the outcome of interval debulking surgery.

     

多肿瘤标记物蛋白芯片在胃癌术前诊断中的价值

目的 探讨多肿瘤标记物蛋白芯片(C-12)在胃癌术前诊断中的价值.方法 应用C-12同时检测12种肿瘤标记物在45例胃癌、38例良性胃病初治患者和65例正常对照血清中的表达水平,寻找与胃癌相关性最强的肿瘤标记物及肿瘤标记物最佳联合检测组合.结果 ①胃癌组中糖链抗原(CA)199、癌胚抗原(CEA)、CA242、CA125和甲胎蛋白的检测阳性率和表达水平显著高于良性胃病组和正常对照组,此外胃癌组中绒毛膜促性腺激素和人生长激素的表达水平也显著高于良性胃病组和正常对照组(P＜0.05).②与胃癌相关性较强的肿瘤标记物是CEA、CA125、CA242和CA199,其中CEA的敏感性、准确性和阴性预测值最高,分别为57.8%、81.8%和77.1%,而CA242检测胃癌的特异性和阳性预测值最高.③胃癌的最佳2项、3项和4项检测组合分别是CEA+CA125、CEA+CA125+CA199和CEA+CA242+CA125+CA199.最佳2项、3项和4项检测组合的敏感性、特异性和准确性与C-12和最佳单项肿瘤标记物相比,差异均无统计学意义(P＞0.05).结论 C-12对胃癌具有较高的术前诊断价值,CEA+CA125、CEA+CA125+CA199和CEA+CA242+CA125+CA199对胃癌的诊断价值足以替代12项肿瘤标记物联合检测.     

Evaluation of preoperative serum markers for individual patient prognosis in stage I–III rectal cancer

Several independent serum biomarkers have been proposed as prognostic and/or predictive markers for colorectal cancer (CRC). To this date, carcinoembryonic antigen (CEA) remains the only recommended serological CRC biomarker. The present retrospective analysis investigates the prognostic value of several serum markers. A total of 256 patients with rectal cancer underwent surgery for curative intent in a university cancer center between January 1988 and June 2007. Preoperative serum was retrospectively analyzed for albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin, bilirubin, CA 125, cancer antigen 19-9, cancer antigen 72-4 (CA 72-4), CEA, CRP, CYFRA 21-1, ferritin, gamma-glutamyl transpeptidase, glutamate oxaloacetate transanunase, glutamate pyruvate transaminase, hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate-dehydrogenase, serum amyloid A (SAA), and 25-hydroxyvitamin D. Cancer-specific survival (CSS) and disease-free survival (DFS) were estimated. Median follow-up time was 8.4 years. Overall 3- and 5-year CSS was 88.6 and 78.9 %, respectively. DFS rates were 72.8 % (3 years) and 67.5 % (5 years). Univariate analysis of CSS indicated aP, CA 72-4, CEA, and SAA as prognostic factors, while aP, CEA, and SAA were also prognostic with regard to DFS. Multivariate analysis confirmed SAA together with T and N stage as prognostic factors. According to UICC stage, CEA and SAA add prognostic value in stages II and III with regard to DFS and CSS, respectively. The combined use of CEA and SAA is able to identify patients with favorable and poor prognosis. In addition to tumor baseline parameters, routine analysis of SAA together with CEA provided markedly improved prognostic value on CSS and DFS in resected rectal cancer.     

Modification of Cutoff Values for HE4, CA125, the Risk of Malignancy Index,and the Risk of Malignancy Algorithm for Ovarian Cancer Detection in Jakarta,Indonesia

Background: CA125 and HE4 are used in calculating Risk of Malignancy Algorithm (ROMA); and Riskof Malignancy Index (RMI). However, studies showed that normal levels of CA125, and HE4 differ amongethnicities such as between Asians and Caucasians, thus affecting the accuracy of the RMI score and ROMA inpredicting ovarian malignancy. This study aimed to determine whether new or modified cutoff values for Ca-125, HE4, the RMI score, and ROMA resulted in a better prediction of malignancy compared with the previousor standard ones. Materials and Methods: Serum level of CA125 and HE4 from 128 patients with diagnosis ofovarian tumor that had been collected before surgery at Cipto Mangunkusumo General Hospital (CMH) inJakarta from November 2010 until May 2011 were reviewed and analysed. The standard cutoff values of thesebiomarkers, RMI, and ROMA were modified by using logistic regression model. The modified cutoff values werecompared to the standard cutoff values in terms of sensitivity, specificity, and accuracy. Results: The modifiedcutoff value of CA125, HE4, RMI score and ROMA were 165.2 U/mL, 103.4 pM, 368.7, 28/54. The sensitivityand specificity of the modified cutoff values CA125, HE 4, RMI score and ROMA in differentiating benign frommalignant and borderline were 67% and 75,4%; 73.1% and 85.2%; 73.1% and 80.3%; and 77.6% and 86.9%.While the sensitivity and specificity of the standard cutoff value of CA125; HE4; RMI score; and ROMA were91% and 24.6%; 83.6% and 65%; 80.6% and 65.6%; and 91.0% and 42.6%. The accuracy of modified cutoffvalues compared with standard cutoff values were: 71.2% vs 59.3%, 78.9% vs 75% vs, 76.5% vs 73.4%, and82% vs 67.9%. Conclusions: The new or modified cutoff values of Ca125, HE4, RMI score and ROMA resultedin higher accuracy compared to the previous or standard ones, at the cost of reduced sensitivity.     

Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer?

Actually, in literature there are not valid tools able to predict the chemotherapy response during first-line ovarian cancer treatment. CA125 and human epididymis protein 4 (HE4) levels of consecutive single-institution patients with epithelial ovarian cancer (EOC) were measured during first-line chemotherapy and until 6 months follow-up. First, patients were divided into two groups according to a temporal criterion: patients treated during 2009 (group A: training group) and patients treated during 2010 (group B: verification group). At sixth months follow-up, patients were sub-classified, within both groups, as platinum resistant or platinum sensitive/intermediate, according to Response Evaluation Criteria in Solid Tumors criteria, and the serum marker courses were further analyzed in each subgroup. Moreover, we performed a logistic regression analysis to choose CA125 and HE4 levels that are best fitted to predict chemoresponse. A total of 76 patients were divided into two groups: group A (n?=?42) and group B (n?=?34). After 6 months of follow-up, 40 patients were classified as platinum sensitive/intermediate and 36 as platinum resistant. At third chemotherapy cycle, in platinum-resistant patients, HE4 levels were >70 pmol/L in 36 of 36 cases, although in platinum-sensitive/intermediate patients, HE4 levels were >70 pmol/L only in six of 40 cases (sensitivity 100 %, specificity 85 %). Moreover, HE4 reduction of almost 47 % at third chemotherapy cycle reached the sensitivity of 83 % with a specificity of 87 % (positive predictive value?=?0.86, negative predictive value?=?0.85) in predicting chemoresponse. On the contrary, CA125 values during chemotherapy did not result statistically significant in predicting platinum response. Our findings suggest that HE4 values during first-line chemotherapy could predict chemotherapy response in EOC patients.     

Application of Joint Detection of AFP,CA19-9, CA125 and CEA in Identification and Diagnosis of Cholangiocarcinoma

Objective: To explore the application of joint detection of serum AFP, CA19-9, CA125 and CEA in identificationand diagnosis of cholangiocarcinoma (CC). Materials and Methods: The levels of serum AFP, CA19-9, CA125and CEA of both 30 patients with CC and 30 patients with hepatocellular carcinoma (HCC) were assessed.Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic effects of single and jointdetection of those 4 kinds of tumor markers for CC. Results: The levels of serum CA19-9, CA125 and CEAin CC patients were higher than that in HCC patients,whereas that of serum AFP was significantly lower s.The area under ROC curve of single detection of serum AFP, CA19-9, CA125 and CEA were 0.05, 0.86, 0.84and 0.83, with the optimal cutoff values of 15.4 ng/ml, 125.1 U/ml, 95.7 U/ml and 25.9 ng/ml, correspondingly,and the percentage correct single diagnosis was <79%. With joint detection, the diagnostic effect of combinedAFP, CA19-9, CA125 and CEA was the highest, with an area under the ROC curve of 0.94 (95%CI 0.88~0.99).Conclusions: Single detection of serum CA19-9, CA125 and EA is not meaningful. The sensitivity, specificity,the rate of correct diagnosis and the area under ROC curve of joint detection of AFP, CA19-9, CA125 and CEAare highest, indicating that the joint detection of these 4 tumor markers is of great importance in the diagnosisof CC.