Sensitive Tumor Marker Research Articles

A sandwich-type photoelectrochemical biosensor based on anthocyanin-sensitized ZnO/P5FIn heterojunction for the sensitive detection of CYFRA21-1.

. A sandwich-type photoelectrochemical (PEC) immunosensor based on a ZnO/poly(5-formylindole) (P5FIn)/anthocyanin heterostructure was developed to achieve sensitive background-free detection ofthe tumor marker CYFRA21-1. ZnO with good photovoltaic properties is combined with narrow bandgap P5FIn to form a p-n type heterojunction. This structure reduces the electron-hole pair recombination, thereby enhancing the photocurrent response of the composite. Anthocyanidins are environmentally friendly natural compounds with excellent antioxidant, redox properties, and remarkable electrochemical activity. After sensitization by anthocyanins, the absorption and utilization of visible light in the composites are enhanced, further improving the PEC luminescence efficiency of the materials. Additionally, boron nitride quantum dots (BN QDs) are combined with Ab2 via polydopamine (PDA) as a secondary antibody marker, enhancing its sensitivity. The biosensor exhibited a linear detection range of 0.001-100ngmL-1 with a limit of detection (LOD) of 0.00033ngmL-1. Furthermore, this biosensor demonstrates excellent selectivity, reproducibility, and stability, as well as successful results in analyzingactual human serum samples. This approach provides a feasible method for tumor marker detection.

Sensitive electrochemiluminescence immunosensor based on a novel luminescent europium metal–organic framework and antenna effect for detecting pro-gastrin-releasing peptide

Sensitive detection of pro-gastrin-releasing peptide (Pro-GRP) is crucial because it is a highly sensitive and specific tumor marker for small cell lung cancer. Herein, we synthesized an efficient luminescent europium metal–organic framework and developed a sandwich ECL immunosensor for the sensitive detection of Pro-GRP, which used Eu3+ as the central ion and 2,4,6-tri (4-carboxyphenyl)-1,3,5-triazine (H3TATB) as the organic ligand. H3TATB acted as a strong absorbing reagent and transferred its energy to Eu3+ via the antenna effect to enhance the ECL response signal of Eu3+. As per calculations, the ECL efficiency of Eu-TATB, which was a promising ECL luminophore, was up to 130 %. The Cu2O cube worked as a substrate to assist the electron transfer and was used as a co-reaction accelerator to catalyze S2O82− to produce more SO4•− and then enhance the ECL intensity of Eu-TATB. Under optimal experimental conditions, the ECL immunosensor had a linear range of 5 fg mL−1–50 ng mL−1 for detecting Pro-GRP with a detection limit of 1.6 fg mL−1; moreover, it demonstrated excellent stability and specificity and has been successfully applied for detecting Pro-GRP in the human serum.

Immune-like sandwich multiple hotspots SERS biosensor for ultrasensitive detection of NDKA biomarker in serum

Developing the rapid, specific, and sensitive tumor marker NDKA biosensor has become an urgent need in the field of early diagnosis of colorectal cancer (CRC). Surface-enhanced Raman spectroscopy (SERS) with the advantages of high sensitivity, high resolution as well as providing sample fingerprint, enables rapid and sensitive detection of tumor markers. However, many SERS biosensors rely on boosting the quantity of Raman reporter molecules on individual nanoparticle surfaces, which can result in nanoparticle agglomeration, diminishing the stability and sensitivity of NDKA detection. Here, we proposed an immune-like sandwich multiple hotspots SERS biosensor for highly sensitive and stable analysis of NDKA in serum based on molecularly imprinted polymers and NDKA antibody. The SERS biosensor employs an array of gold nanoparticles, which are coated with a biocompatible polydopamine molecularly imprinted polymer as a substrate to specifically capture NDKA. Then the biosensor detects NDKA through Raman signals as a result of the specific binding of NDKA to the SERS nanotag affixed to the capture substrate along with the formation of multiple hotspots. This SERS biosensor not only avoids the aggregation of nanoparticles but also presents a solution to the obstacles encountered in immune strategies for certain proteins lacking multiple antibody or aptamer binding sites. Furthermore, the practical application of the SERS biosensor is validated by the detection of NDKA in serum with the lower limit of detection (LOD) of 0.25 pg/mL, meanwhile can detect NDKA of 10 ng/mL in mixed proteins solution, illustrating high sensitivity and specificity. This immune-like sandwich multiple hotspots biosensor makes it quite useful for the early detection of CRC and also provides new ideas for cancer biomarker sensing strategy in the future.

Diagnostic Performance of Magnetic Resonance Imaging for Pediatric Ovarian Neoplasms: A Multi-Institutional Review

Study ObjectiveTo assess diagnostic performance of MRI to predict ovarian malignancy alone and compared to other diagnostic studies. MethodsRetrospective analysis of patients aged 2 to 21 years who underwent ovarian mass resection between 2009-2021 at eleven pediatric hospitals. Sociodemographic information, clinical and imaging findings, tumor markers, and operative and pathology details were collected. Diagnostic performance for detecting malignancy was assessed by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for MRI with other diagnostic modalities. Results1,053 patients underwent resection of an ovarian mass with a median age of 14.6 years; 10% (110/1053) had malignant disease on pathology and 13% (136/1053) underwent preoperative MRI. MRI sensitivity, specificity, PPV, and NPV were 60%, 94%, 60%, 94%. Ultrasound sensitivity, specificity, PPV, and NPV were 31%, 99%, 73%, 95%. Tumor marker sensitivity, specificity, PPV, and NPV were 90%, 46%, 22%, 96%. MRI and ultrasound concordance was 88% with sensitivity, specificity, PPV, and NPV of 33%, 99%, 75%, 94%. MRI sensitivity in ultrasound-discordant cases was 100%. MRI and tumor marker concordance was 88% with sensitivity, specificity, PPV, and NPV of 100%, 86%, 64%, 100%. MRI specificity in tumor marker-discordant cases was 100%. ConclusionDiagnostic modalities used to assess ovarian neoplasms in pediatric patients typically agree. In cases of disagreement, MRI is more sensitive for malignancy than ultrasound and more specific than tumor markers. Selective use of MRI with preoperative ultrasound and tumor markers may be beneficial when the risk of malignancy is uncertain. Concise AbstractThis retrospective review of 1053 patients age 2-21 years who underwent ovarian mass resection between 2009-2021 at 11 pediatric hospitals found that ultrasound, tumor markers, and MRI tend to agree on benign vs malignant but in cases of disagreement, MRI is more sensitive for malignancy than US.

Practical application of the CA-62 tumor marker in the initial diagnosis of oncological disease of epithelial origin: assistance to the doctor in interpreting the results

Aim. Demonstration the possibility of practical application of the highly sensitive tumor marker CA-62 in the initial diagnosis in asymptomatic patients with suspected cancer and/or the presence of pathological changes in instrumental studies, as well as describe the criteria for interpreting the results to help the doctor make a decision.
 Materials and methods. The article used the results and conclusions of blind clinical trials conducted to detect early stages of breast cancer (BC), prostate cancer (PC), colorectal cancer (CRC) and non-small cell lung cancer using the CA-62 tumor marker and other tumor markers. Statistical analysis was performed using the MedCalc program (MedCalc Software Ltd, Belgium). Diagnostic efficiency was assessed in terms of sensitivity, specificity, test accuracy, PPV and NPV, ROC analysis. The significance level was taken as p0.001.
 Results. The use of the standard cut-off value of 5000 U/ml of the CA-62 tumor marker makes it possible to achieve 97% sensitivity with 95% specificity in stage I BC. The combination of tumor markers CA-62 and CA 15-3 allows achieving 100% specificity in differentiation of BC and benign breast hyperplasia. The use of the CA-62 marker (6500 U/ml) in the gray zone of PSA 2.510 ng/ml improves the accuracy of detecting PC in biopsy from 35 to 93.1% with 90% sensitivity and 97% specificity. The use of a combination of tumor markers (CA-625000 U/ml, CYFRA 21-12.5 ng/ml and CEA5 ng/ml) will allow the doctor to improve the efficiency of differentiating lung cancer from chronic obstructive pulmonary disease. The combined use of markers (CEA3.5 ng/ml) and (CA-625000 U/ml) achieves 100% specificity with 97% sensitivity in detecting early stages of CRC.
 Conclusion. The article shows the possibilities of using the CA-62 marker, as well as new algorithms for the detection and differentiation of early stages of BC, PC, non-small cell lung cancer and CRC and benign neoplasms using the CA-62 marker in primary diagnosis. The use of the CA-62 tumor marker or its combination with other diagnostic methods can be a useful strategy for a comprehensive assessment of the risk of malignant neoplasms and increasing the diagnostic sensitivity of detecting early stages of cancer.

Detection of CYFRA 21-1 in human serum by an electrochemical immunosensor based on UiO-66-NH2@CMWCNTs and CS@AuNPs.

In this study, an electrochemical immunosensor was constructed to detect the cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) in human serum. CYFRA 21-1 is the most sensitive tumor marker of non-small cell lung cancer (NSCLC), its content in normal human serum should be less than 3.3ng/mL. When lung cancer cells dissolve or die, a myriad of CYFRA 21-1 is released into a tumor patient's blood circulation, and its serum content elevates strikingly. Consequently, detecting CYFRA 21-1 by an electrochemical biosensor is expected to provide a new method for the early detection and prevention of lung cancer. In this study, a composite of UiO-66-NH2 and carboxylated multi-walled carbon nanotubes (CMWCNTs) was used as the substrate material of a sensor; the resulting sensor had a large specific surface area and strong electrical conductivity. Moreover, gold nanoparticles (AuNPs) were used to bind to antibodies through an Au-S bonds. Also, a supersensitive detection of CYFRA 21-1 was achieved through the specific bindings of antigens and antibodies. Under optimal detection conditions, the change of current signal intensity of the immunosensor was proportional to the logarithm of CYFRA 21-1 concentration and had a linear relation in the range of 0.005-400ng/mL, while the detection limit was 1.15pg/mL (S/N=3). The proposed immunosensor had high precision, stability, and selectivity. More importantly, the sensor was been successfully applied to detect CYFRA 21-1 in human serum with high recovery, providing a new method for early screening and dynamic monitoring of lung cancer.

Serum and Cellular Biologic Tumor Markers in Testicular Cancer

During the past two decades, a dramatic improvement has been made in the treatment of testicular germ cell tumor. This progress has been dueto finding more efficacious systemic chemotherapeutic agents and the availability of specific and sensitive biologic tumor markers to detect early recurrence and monitor the therapy. In this review, i will update my 15 years of experience in establishing and utilization of these serum and cell markers in testicular cancer.

Construction of Magnetic Core-Large Mesoporous Satellite Immunosensor for Long-Lasting Chemiluminescence and Highly Sensitive Tumor Marker Determination.

Chemiluminescence immunoassay exhibits high sensitivity and signal-to-noise ratio, thus attracting great attention in the early diagnosis and dynamic monitoring of diseases. However, the collection of conventional flash-type chemiluminescence signal (<5s) relies heavily on automatic sampling and reading instrument. Herein, a novel core-satellite multifunctional chemiluminescence immunosensor is designed for the efficient enrichment and highly sensitive determination of cancer biomarker carcinoembryonic antigen (CEA) with enhanced and long-lasting output signal that can be conveniently recorded by a simple microplate plate reading instrument. Anti-CEA monoclonal antibody 2 (Ab2) modified Fe3 O4 @SiO2 microspheres (Fe3 O4 @SiO2 -Ab2, 370nm in diameter) are synthesized as the core for selectively capturing and enriching target CEA in solution, and anti-human CEA monoclonal antibody 1 (Ab1) and horseradish peroxidase (HRP) co-immobilized dendritic large-mesoporous silica nanospheres (MSNs-HRP/Ab1, 80nm in diameter, pore size: 17nm) are synthesized as the satellite for efficient immunological recognition and signal amplification. The as-designed core-satellite magnetic chemiluminescence immunosensors exhibit a broad linear range of 0.01-20ngmL-1 and a low detection limit of 3.0pgmL-1 for the convenient, highly specific, and sensitive determination of CEA in human serum. Such core-satellite chemiluminescence immunosensors are expected to act as a powerful tool for in vitro detection of various biomarkers, overcome the defect of conventional chemiluminescence relying heavily on expensive and bulky automatic instruments and popularize chemiluminescence analysis to primary medical institutions and remote areas.

Significance of Thyroglobulin Autoantibodies in Patients With Thyroid Cancer Treated With Lenvatinib

Abstract Context Serum thyroglobulin (Tg) is a highly sensitive and specific tumor marker, employed in post-operative management of patients with differentiated thyroid carcinomas. Tumor shrinkage of radioiodine-refractory thyroid cancer (RAIR-DTC) treated with multitarget kinase inhibitors as lenvatinib, expressed according to the Response Evaluation Criteria in Solid Tumors (RECIST), is also associated with a drastic reduction of Tg levels. However, interference caused by circulating thyroglobulin autoantibodies (TgAb) represents the main limitation in the clinical use of Tg. Objective To evaluate if in RAIR-DTC TgAb could be considered a surrogate marker of Tg in monitoring response to treatment with lenvatinib. Design We retrospectively evaluated patients who had started lenvatinib and correlated serum Tg and TgAb with the radiological response across visits. Setting University of Pisa, Italy. Patients We selected 9/97 RAIR-DTC patients with detectable TgAb. Intervention None. Main Outcome Measure(s) None. Results Tg values correlated neither with TgAb title nor with radiological response across visits. Greater decreases in TgAb titer correlated with favorable radiological response to lenvatinib after 1 month (Spearman's correlation = 0.74, P = .021) and 6 months (correlation = 0.61, P = .079). According to RECIST, patients with partial response showed a ∼10-fold greater decrease in TgAb compared to those with stable disease at 1 month (median TgAb decrease: −142 vs −14 IU/mL, P = .01) and those with progressive disease at 6 months (median TgAb decrease: −264 vs−24 IU/mL, P = .04). Conclusion TgAb evaluation may represent a reliable surrogate marker for Tg trend in evaluating response of RAIR-DTC to treatment with lenvatinib. A multicentric study would be useful to confirm our results.

Plasmonic metasurface enhanced by nanobumps for label-free biosensing of lung tumor markers in serum

Plasmonic metasurface biosensing has excellent potential in label-free detection of tumor biomarkers. In general, a variety of plasmonic metasurface nanofabrication leads to various degree of metallic surface roughness. However, the metasurface roughness effects on plasmonic sensing of tumor markers have been barely reported. Here we fabricate high-roughness (HR) gold nanohole metasurfaces with nanobumps and investigate their biosensing in comparison with the low-roughness (LR) counterparts. The HR metasurfaces demonstrate the surface sensitivity of multilayer polyelectrolyte molecules, which is 57.0% higher than the LR ones. The HR metasurfaces also illuminate higher immunoassay sensitivity to multiple lung cancer biomarkers, including carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 21–1. The highest increasement of tumor marker sensitivity is up to 71.4%. The biosensing enhancement is attributed to the introduction of gold nanobumps on metasurfaces, which provides more hot-spot regions, higher localized near-field intensity and better optical impedance matching. Furthermore, the biosensing of HR metasurfaces effectively covers the threshold values of tumor markers for early lung cancer diagnosis, and is used for the detection of clinical serum samples. The testing deviation is less than 4% compared with commercial immunoassay, which implies promising applications on medical examinations. Our research provides a scientific guide to surface roughness engineering for plasmonic metasensing in the future point-of-care testing.

Experience of King Abdullah Medical City in Bone Metastases Detection by Different Radiological Modalities and Tumor Marker Sensitivity

RSSA conference&#x0D; Abstract&#x0D; Objective&#x0D; The study aims to evaluate the detectability of bone metastases (BM) by CT scan vs. bone&#x0D; Scintigraphy (BS) and the sensitivity of tumor markers in different oncological settings for predicting the presence of skeletal metastases.&#x0D; Methods&#x0D; Medical information was collected for 299 patients who fit the inclusion criteria from patient files and medical image reports using (AGFA PACS® and Trakcare® systems) between January 2013 and December 2021 at KAMC-HC in Makkah.&#x0D; Results&#x0D; BS detected BM in breast cancer patients in 135 cases, while CT scan detected BM in 122 cases. In prostate cancer patients, the BS detected BM in all 38 cases, while the CT scan detected BM in 32 cases. Regarding Gastro-Intestinal (GI) malignancies, the BS detected BM in 27 cases, while the CT scan detected BM in 23 cases only.&#x0D; PSA was conducted on 40 patients and 28 (70%) of them were elevated. Breast cancer patients showed tumor marker elevation in 46 (38.9%) of 118 patients. GI malignancy revealed the highest rate of tumor markers elevation in 24 (80%) of 30 patients.&#x0D; Conclusion&#x0D; Our study showed that BS has higher sensitivity than CT scan in detecting BM for breast, prostate and GI malignancies. Further collaboration is needed to determine the sensitivity of each modality, compare them with other monitoring methods like MRI or PET/CT, optimize the hospital resources utilization for each type of malignancy and reduce the patient’s exposure to unnecessary radiation.&#x0D; &#x0D; &#x0D;

A highly sensitive turn‐off fluorescent probe based on 2D Eu(III)‐MOFs nanosheets for glutathione in vitro and living cells

AbstractGlutathione (GSH) is generally used as an effective and sensitive tumor marker because its abnormal levels are associated with high free radical level in tumor. In this work, GSH could be easily detected by a kind of designed Eu‐based metal–organic frameworks (Eu‐MOFs, named Eu(DTBA)) fluorescent sensor. Due to the “antenna effect” of 4,4′‐dithiobenzoic acid (4,4′‐DTBA) ligands on Eu3+, Eu(DTBA) emits the strong characteristic red light of Eu3+ under ultraviolet excitation. Moreover, the emission intensity strongly depends on GSH concentrations. Thus, Eu(DTBA) can serve as a turn‐off fluorescent switch of GSH because its framework structure can easily be destroyed by GSH that leads to the fluorescence quenching. Remarkably, during sensing GSH, Eu(DTBA) has shown many appealing performances, such as broad a response window (0–20 mM), fast response (3 min), high sensitivity (LOD = 0.35 µM), and excellent anti‐interference ability. The real bioimaging application has demonstrated that the reported Eu(DTBA) can be used as an excellent bioimaging agent to successfully distinguish tumor cells from normal cells in clinical diagnosis.

Gliomas molecular markers: importance in treatment, prognosis and applicability in brazilian health system.

Gliomas represent 80% of all primary malignant brain tumors in adults. In view of this public health problem, the early detection through sensitive and specific molecular tumor markers analysis can help to improve gliomas diagnosis and prognosis as well as their staging, assessment of therapeutic response and detection of recurrence. Therefore, this review focuses in current gliomas tumor markers, IDH-1/2, 1p/19q, MGMT, ATRX, TERT, H3, EGFR, BRAF and Ki67 used in clinic worldwide and their importance to early detection, glioma histological and molecular classification as well as in predicting patient's therapeutic response. In addition, we present what are the steps in the requesting process for this type of examination in the Brazilian Public Health System (SUS) scope, which attends most of the Brazilian population. Thereby, this article is useful in demonstrating which markers are used in the clinical practice for glioma patients and can be performed in the SUS through partnerships/agreements between specialized health centers and clinical analysis laboratories. It is hoped that this work clarifies, the necessary subsidies to carry out the research of tumor markers in all institutions that serve SUS users, providing a service with equal conditions.

Exosome Component 4 Promotes Epithelial Ovarian Cancer Cell Proliferation, Migration, and Invasion via the Wnt Pathway.

BackgroundOf gynecologic malignancies, ovarian cancer is the leading cause of death, mainly due to the lack of sensitive tumor markers, which means it almost always presents at an advanced stage. Exosome Component 4 (EXOSC4) is involved in RNA degradation, but its role in epithelial ovarian cancer (EOC) is unclear.MethodsThe expression levels of EXOSC4 in EOC and normal ovarian tissue specimens were determined by immunohistochemical staining. The overall survival (OS) and progression-free survival (PFS) of patients with EOC were evaluated after patients were classified into high and low EXOSC4 expression groups, and the Cox regression model was established to identify independent predictors of patient prognosis. The effects of EXOSC4 on proliferation, colony formation, migration, and invasion were examined in the SKOV-3 and HO8910 cell lines by lentivirus-mediated shRNA knockdown. Flow cytometry was used to detect cell cycle changes. The mRNA levels of cyclin D1, CDK4, and c-myc were detected by RT-PCR. The protein expression levels of β-catenin, cyclin D1, CDK4, c-myc, vimentin, N-cadherin, and E-cadherin were assessed by western blot. Wnt/β-catenin activation was measured by TCF/LEF reporter assay.ResultsEXOSC4 was significantly elevated in EOC tissues and cell lines. High EXOSC4 expression was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and pathological grade, and identified as an independent predictor of shorter OS and PFS. EXOSC4 knockdown suppressed proliferation, migration, and invasion in EOC cell lines. Cells were arrested at G0/G1 phase after EXOSC4 knockdown. The mRNA levels of cyclin D1, CDK4, and c-myc were decreased. β-catenin, cyclin D1, CDK4, c-myc, vimentin, and N-cadherin protein expression levels were reduced, while those of E-cadherin was increased. Wnt/β-catenin activity was suppressed after the EXOSC4 knockdown.ConclusionsEXOSC4 is involved in EOC. Knockdown of EXOSC4 can inhibit the proliferation, migration, and invasion ability of EOC by suppressing the Wnt pathway. EXOSC4 is expected to be a novel biomarker and molecular target in EOC.

Correlation between serum PSA, gleason score and histopathological grading of adenocarcinoma of prostate in patients undergoing TRUS guided prostatic biopsy in a tertiary care centre of Southern India

Background Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths worldwide. Serum psa, a glycoprotein and a serine protease, which is increased in all prostatic diseases but markedly elevated levels are indicative of carcinoma prostate. The present study was done to evaluate the histopathologyof carcinoma of prostate in trus guided prostatic biopsy specimens and correlate serum psa levels with gleason score and grade groups. Methods A hundred patients presented with luts and suspicious of carcinoma prostate underwent trus guided 16 core prostatic biopsy. Histopathological examination, gleason scores and grades of biopsies were obtained. Based on the gleason scores, patients with carcinoma of the prostate were divided into five-grade groups. Mean serum psa levels were calculated and correlated with gleason score and grade groups. Results Malignancy was found in 69 per cent of cases, of which 68 patients were found to have adenocarcinoma of the prostate, one patient found to have undifferentiated carcinoma of the prostate. The total number of patients in each gleason grade groups were obtained, and the mean serum psa levels of these patients in each group were calculated. Mean serum psa levels in each group are group 1 (21.3 ng/ml), group 2 (58.4 ng/ml), group 3 (73.6 ng/ml), group 4 (118.4 ng/ml), group 5 (96.3 ng/ml). Conclusion Serum psa is a highly sensitive tumour marker with low specificity, and its levels are increased in many benign and iatrogenic conditions. Psa has a high negative predictive value which is essential in ruling out malignancy. In our study, higher serum psa levels were correlated with higher gleason score and grades.

Cytomorphological analysis of histologically confirmed cases of medullary thyroid carcinoma

Abstract Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignant tumor of parafollicular C-cell origin of the thyroid gland, whose tumor cells typically produce calcitonin. The serum level of calcitonin produced by tumor cells is a sensitive tumor marker. An elevated serum level of this and the simultaneous presence of a thyroid nodule confirmed by ultrasound raise a reasonable suspicion of MTC. Still, the first-line MTC confirmation method in diagnosing MTC is fine-needle aspiration cytology (FNA). Objective: The aim of our study was the clinicopathological and cytomorphological analysis of histologically confirmed MTC cases obtained with FNA, as well as their comparison with the clinicopathological and cytomorphological characteristics of papillary thyroid carcinoma (PTC). Material and method: In our retrospective study, we analyzed the FNA cytology findings of patients with nodular goiter examined between 2013-2019 and the available clinical data. Results: In the 7-year period, 1,808 fine-needle aspiration examinations were performed, of which we identified 12 MTC and 77 PTC cases. The average age of patients diagnosed with MTC was 53±13 years. There were nine women and three men in examined cases. The average diameter of the nodules was 14±5 mm. All of our cases were of the sporadic type. The average age of patients diagnosed with MTC was greater than that of patients diagnosed with PTC (53 vs. 44 years, p=0.02367). A female predominance is observed in both diseases, although this is more pronounced in PTC. The diameter of the MTC nodules does not differ significantly from the mean size of the PTC nodules (14 vs. 17 mm, p=0.3138). The cytomorphological characteristics of the MTC cases we examined correspond to those described in the international literature, with minor differences. Conclusions: MTC is one of the rarer thyroid cancers, which is often difficult to distinguish from other types of thyroid cancer based on clinical features alone. Average age at diagnosis is greater than patients with PTC. Accurate diagnosis is critical as it requires a different approach than other types of thyroid cancer, it may require a different surgical approach, and may benefit from targeted therapy. Therefore, knowledge of the cytomorphology of MTC is essential for accurate diagnosis and optimal patient care.

Viral Hepatitis and Hepatocellular Carcinoma: State of the Art

Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.

Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer.

Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemoradiation or to predict relapse during the follow-up period. We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV E7 gene as a marker for residual disease compared to HPV integration site and PIK3CA mutations. Finally, the prognostic impact of circulating HPV E7 gene was assessed with its prediction value of relapse. HPV E7 gene was the most sensitive tumor marker, superior to both HPV integration sites and PIK3CA mutations in serum. Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (P = 0.02) and para-aortic lymph node involvement (P = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R = 0.39, P < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (P < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2-15) from HPV ctDNA detection. HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.See related commentary by Wentzensen and Clarke, p. 5733.

DIAGNOSTIC SIGNIFICANCE OF SERUM CA242, CA19.9 AND CEA IN DIAGNOSIS OF GALL BLADDER CANCER

Background: Tremendous progress of imaging technique does not result in early diagnosis of gall bladder cancer. In search of effective, inexpensive and non-invasive tool tumour markers shows promise. Serum CA242, CA19.9 and CEA are evaluated for this purpose. Aim and objective: To evaluate diagnostic signicance of serum CA242, CA19.9 and CEAin gall bladder cancer either alone or in combination. Material and methods: It was an analytical cross sectional study done in Indira Gandhi Institute of medical Sciences. These markers were measured in 70 cases of gall bladder cancer and 70 healthycontrols. Serum CA242 was done by ELISA assay as per instruction given in pack insert (CD diagnostic). Serum CA19.9 and CEA were done by CLIA technique by Assess 2 analyser. Results: Mean value of these tumour marker were increased in gall bladder cancer group (p&lt;0.001). CA19.9 was most sensitive tumourmarker (79.5%). Serum CA 242 was most specic test (83.3%) for diagnosis of gall bladder cancer among the three-tumour marker. On combination of tumour marker sensitivity (87.5%) and specicity (89.5%) were increased. In ROC curve analysis area under curve (AUC) for CA242 was highest. Conclusion: Combination of these tumour markers can be used as screening tool for gall bladder cancer.

The Importance of Lymph Node Dissection in Medullary Thyroid Carcinoma Management

Abstract Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy that arises from calcitonin (Ct) parafollicular C-cells. Most cases are sporadic with frequent presentation being a solitary thyroid nodule. Total thyroidectomy with central neck dissection of lymph nodes (LN) is the standard treatment for MTC. The need for lateral neck dissection is controversial, with poor efficacy of non-surgical treatments presenting a problem. We present a case of MTC with preoperative Ct &amp;gt;500 pg/mL and negative imaging for metastases who underwent total thyroidectomy without LN exploration with an excellent postoperative biochemical response. This is a case of a 52-year-old female with a three-year history of anterior neck growth. The repeat fine needle aspiration (FNA) of a, previously negative for malignancy, growing nodule was consistent with MTC. Preoperative Ct and CEA levels were significantly elevated, 834.0 pg/mL and 11.2 ng/dL, respectively; a preoperative pan- CT scan did not reveal any suspicious LN or metastatic lesions and a negative RET oncogene mutation with normal plasma normetanephrines and metanephrines suggested a spontaneous rather than familial MTC. Patient underwent total thyroidectomy without LN exploration. Pathology confirmed MTC stage T1b. The one and three months postoperative follow up showed a significant downtrend with no normalization of Ct and CEA levels, 9.1 – 9.2 and 11.1 – 1.2, respectively. Reoperation for central and lateral neck dissection was considered; however, given the excellent biochemical response as well as the lack of radiographic evidence of disease, it was decided to continue monitoring of Ct and CEA levels for now. MTC response is monitored by the postoperative serum Ct and CEA levels when compared to the preoperative values. Serum Ct serves as a sensitive tumor marker, which is thought to have correlation with malignancy mass size and its cellular differentiation. The term biochemically cured, refers to the postoperative normalization of CEA and undetectable levels of Ct which carries a 5-year recurrence of 5%. It is believed that the higher the levels and the faster doubling time of these tumor markers the worse is the prognosis. In addition, it is suggested that patient’s age and extent of disease at the time of surgery are proportionally correlated with disease recurrence. However, there are reports of large MTC metastatic deposits with low serum Ct and CEA, rising up the hypothesis that levels reflect cell production potential for tumor markers rather than the number of cells. Reoperation rarely results in biochemical cure, but it may slow disease progression. Normal postoperative Ct levels predict cure; however, the clinical course of those with upper normal limit levels postoperatively is markedly variable. Careful regular biochemical and imaging follow-up will be of the utmost importance for the patient presented in this case.