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Background: In patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), we aimed to develop a novel blood-based biomarker utilizing a gene-expression profile for the detection of pancreatic malignancies, such as IPMN-derived carcinoma (IPMC) or pancreatic ductal adenocarcinoma (PDAC)., Patients and Methods: We enrolled 40 patients with pancreatic tumors (24 BD-IPMNs, four IPMCs and 12 PDACs) and identified the characteristic gene-expression profiles in pancreatic malignancies. Subsequently, we constructed a gene-expression scoring system for the proper diagnosis of pancreatic malignancies. The result was validated in 14 patients (five IPMNs, three IPMCs and six PDACs)., Results: The scoring system utilizing the expression levels of 13 genes showed high diagnostic yield (sensitivity=94.0%, specificity=92.0% and area under the curve=0.94), which was confirmed in the validation set. Furthermore, its diagnostic yield was not reduced even in early-stage pancreatic malignancies (sensitivity=85.0%, specificity=93.0% and area under the curve=0.88)., Conclusion: We developed a blood-based gene expression scoring system for cancer screening in patients with BD-IPMNs., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Intraductal papillary mucinous neoplasms (IPMNs) are presumed to evolve from low-grade dysplasia to high-grade dysplasia to invasive carcinoma. Resection of lesions before the development of pancreatic cancer may prevent the development of an incurable process as, once IPMNs progress to invasive cancer, the prognosis may be as poor as resected conventional pancreatic ductal adenocarcinoma. Resection of IPMNs, particularly in the setting of high-grade dysplasia, is presumed to provide a survival benefit. IPMNs also present many challenges as the identification of high-grade dysplasia and early invasive carcinoma and the timing and frequency of malignant progression are not yet established. The limited predictive accuracy presents a challenge as pancreatic resection is associated with a risk of substantial morbidity and mortality; 20-30% and 2-4%, respectively. Diagnostic armamentarium contains pancreas-protocol computed tomography (CT) scan, gadolinium-enhanced magnetic resonance imaging (MRI) with or without magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS). The most promising method is endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as this technique allows analysis of cyst fluid using biomarkers. Until now, in clinical practice, we utilize two biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9); however, DNA analysis of pancreatic cystic fluid and genomic analysis could offer new tools to the diagnosis and administration of IPMNs. Novel genomic and serum biomarkers could play an important future role to identify those individuals who will benefit from an early operation and those who will benefit from watchful waiting approach. More prospective studies are needed., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: The aim of this study was the development of a multiplex-PCR assay for the detection of circulating tumor cells in patients with colorectal and gastric cancer., Patients and Methods: Peripheral blood samples were collected from 81 patients with colorectal cancer, 16 with gastric cancer and 38 healthy blood donors, as controls. The samples were processed for RNA extraction and cDNA synthesis and were subsequently analyzed for the expression of cytokeratin 19 (CK19), cytokeratin 20(CK20) and epidermal growth factor receptor (EGFR) with multiplex PCR., Results: Statistical analysis revealed that the combination of CK19 and CK20 could be useful in the exclusion of colorectal cancer, as well as the diagnosis and exclusion of gastric cancer. Furthermore, the expression of EGFR was correlated with the presence of systemic disease in patients with colorectal cancer., Conclusion: Multiplex-PCR-based detection of circulating tumor cells could serve as a useful tool for the diagnosis, and monitoring of patients with colorectal and gastric cancer., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: 8-Hydroxydeoxyguanosine (8-OHdG) is a marker of oxidative stress in DNA. This study was undertaken to reveal whether serum 8-OHdG could be a prognostic factor in epithelial ovarian carcinoma (EOC)., Patients and Methods: Preoperative serum 8-OHdG levels were examined by enzyme-linked immunosorbent assay in 84 stage I-IV EOC patients. Immunohistochemical (IHC) 8-OHdG expression was determined in 78 of these patients., Results: Strong 8-OHdG immunostaining predicted poor survival. High serum 8-OHdG (>140 pg/ml) was associated with poor ovarian cancer-specific survival (p<0.05) in patients with grade 1-2 EOC (p<0.05), but was not observed among the grade 3 patients. High 8-OHdG levels both in the serum and in the tumour tissue was associated with traditional factors of poor prognosis and serous histology., Conclusion: Both serum and IHC 8-OHdG assessment may serve as prognostic tools in EOC and the role of oxidative stress as a carcinogenic factor in ovarian cancer pathogenesis is also suggested.

Background: The aim of this study was to measure several parameters in patients with early-stage colorectal cancer (CRC) and to evaluate them for their utility in routine clinical practice., Patients and Methods: Pre-operative serum levels of the following parameters were measured in 174 patients with CRC (clinical stage I-III): carcinoembryonic antigen (CEA), carbohydrate antigen CA 19-9, proliferative marker thymidine kinase (TK), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS), interleukin-6 (IL-6), interleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor (VEGF), C-peptide, insulin, adiponectin and leptin. The control group consisted of 50 patients who were undergoing a complete preventive medical examination and in these patients at the time of blood collection there was no evidence of any cancer disease., Results: Significant increase of the following parameters was found in patients with CRC: CEA, CA 19-9, TPA, IL-6, IL-10, TIMP-1, C-peptide, insulin and adiponectin. Only two of these, CA 19-9 and adiponectin, represent highly unfavorable prognostic factors. If elevated, they affect both progression-free interval and overall survival., Conclusion: Based on our results, we can conclude that none of the measured parameters fulfills the criteria for use for screening nor for primary diagnosis of CRC. Some of the parameters are important for prognosis estimate: Elevated CA 19-9 is related to an unfavorable prognosis, in terms of cancer recurrence and mortality rate. Angiogenetic factor VEGF represents a prognostic factor important for OS. CEA represents a parameter which is related to disease progression. Interleukins seem to be prospective complementary tumor markers. Adiponectin may be used for estimation of advanced stage of cancer and for estimate of risk of cancer recurrence.

In 180 patients with epithelial ovarian cancer and 214 women with benign pelvic pathologies, serum levels of TATI (cut-off point 21 ng ml-1) and CA 125 (cut-off point 35 U ml-1) were determined. Data were correlated with tumour stage, histological type and tumour grade. Overall, when used as a single marker, TATI showed a sensitivity of 63% and a specificity of 72%, whereas the sensitivity and specificity of CA 125 > 35 U ml-1 were 80% and 82% respectively. A combination of the two markers increased the sensitivity to 91% (TATI > 21 ng ml-1 or CA 125 > 35 U ml-1), whereas the specificity decreased to 65%. TATI was clearly superior in diagnosing mucinous carinomata of the ovaries; the rate of true positive findings was 64% versus 50% for CA 125. Unlike CA 125, TATI levels correlated well with tumour grade. In conclusion, CA 125 remains the single tumour marker of choice in the diagnosis of malignant epithelial ovarian cancer, while TATI appears to be a valuable complementory marker with a higher sensitivity in cases of poorly differentiated and mucinous carcinomata.

We compared the tumour marker CA 72-4 and the new markers CASA and CYFRA 21-1 with the established marker CA 125II in follow-up care and control of efficacy of treatment in ovarian cancer in order to determine whether there are differences in recognizing ovarian carcinomas of different histological type. The investigation was done retrospectively on serum samples frozen at -80 degrees C obtained from 262 subjects, among them 50 healthy women, 53 sera with benign gynecological diseases and 159 sera with ovarian cancer, 72 of them at the time of primary diagnosis. We used commercially available kits: CA 125 II: Centocor RIA, CASA: Medac EIA, CA 72-4: Centocor RIA and CYFRA 21-1: Boehringer EnzymunR ELISA. Fixing specificity at 95% versus benign gynecological diseases as a clinically relevant reference group, we found cut-off values of 160 U/mL for CA 125II, 6.5 U/mL for CASA, 6.8 U/mL for CA 72-4 and 2.4 ng/ml for CYFRA 21-1. Based on this specificity we can compare the corresponding sensitivities at the time of primary diagnosis (n = 72): CA 125 II 47%, CA 72-4 47%; CASA 31% and CYFRA 21-1 44%. Regarding histological types of ovarian carcinomas, we found a sensitivity of 50% for CA 125 II and CASA, 36% for CA 72-4 and 33% for CYFRA 21-1 in serous ovarian cancer (n = 53), 21% for CA 125 II and CASA, 36% for CYFRA 21-1 and 43% for CA 72-4 for mucinous ovarian cancer (n = 27). Serous ovarian carcinomas were classified by higher FIGO-stages than mucinous ovarian carcinomas. Additional sensitivities were found at the time of primary diagnosis for the combination of CA 125 II and CA 72-4 and in serous ovarian cancer for CA 125 II and CASA. According to our results, at the time of primary diagnosis the combined determination of CA 125 II and CA 72-4 is useful. If both are negative, determination of CASA can be helpful. For follow-up care and control of efficacy of treatment the preoperative positive or leading marker is sufficient.