Sensors Based on Molecularly Imprinted Polymers in the Field of Cancer Biomarker Detection: A Review.

Biomarkers play a pivotal role in the screening, diagnosis, prevention, and post-treatment follow-up of various malignant tumors. In certain instances, identifying these markers necessitates prior treatment due to the complex nature of the tumor microenvironment. Consequently, advancing techniques that exhibit selectivity, specificity, and enable streamlined analysis hold significant importance. Molecularly imprinted polymers (MIPs) are considered synthetic antibodies because they possess the property of molecular recognition with high selectivity and sensitivity. In recent years, there has been a notable surge in the investigation of these materials, primarily driven by their remarkable adaptability in terms of tailoring them for specific target molecules and integrating them into diverse analytical technologies. This review presents a comprehensive analysis of molecular imprinting techniques, highlighting their application in developing sensors and analytical methods for cancer detection, diagnosis, and monitoring. Therefore, MIPs offer great potential in oncology and show promise for improving the accuracy of cancer screening and diagnosis procedures.

Enhancing the diagnostic accuracy of colorectal cancer through the integration of serum tumor markers and hematological indicators with machine learning algorithms.

BACKGROUND: Colorectal cancer has a high incidence and mortality rate due to a low rate of early diagnosis. Therefore, efficient diagnostic methods are urgently needed. PURPOSE: This study assesses the diagnostic effectiveness of Carbohydrate Antigen 19-9 (CA19-9), Carcinoembryonic Antigen (CEA), Alpha-fetoprotein (AFP), and Cancer Antigen 125 (CA125) serum tumor markers for colorectal cancer (CRC) and investigates a machine learning-based diagnostic model incorporating these markers with blood biochemical indices for improved CRC detection. METHOD: Between January 2019 and December 2021, data from 800 CRC patients and 697 controls were collected; 52 patients and 63 controls attending the same hospital in 2022 were collected as an external validation set. Markers' effectiveness was analyzed individually and collectively, using metrics like ROC curve AUC and F1 score. Variables chosen through backward regression, including demographics and blood tests, were tested on six machine learning models using these metrics. RESULT: In the case group, the levels of CEA, CA199, and CA125 were found to be higher than those in the control group. Combining these with a fourth serum marker significantly improved predictive efficacy over using any single marker alone, achieving an Area Under the Curve (AUC) value of 0.801. Using stepwise regression (backward), 17 variables were meticulously selected for evaluation in six machine learning models. Among these models, the Gradient Boosting Machine (GBM) emerged as the top performer in the training set, test set, and external validation set, boasting an AUC value of over 0.9, indicating its superior predictive power. CONCLUSION: Machine learning models integrating tumor markers and blood indices offer superior CRC diagnostic accuracy, potentially enhancing clinical practice.

Diagnostic potential of protein serum biomarkers for distinguishing small and non-small cell lung cancer in patients with suspicious lung lesions.

BACKGROUND: Biomarkers play a role in identifying, managing, and predicting cancer outcomes. In lung cancer, they are used at various time points. Doubts remain regarding their accuracy for differential diagnosis and histological subtyping. A diagnostic test study was conducted. It included malignant lesions and controls with benign lesions. Before lung biopsy, all patients had the following biomarkers measured in serum (Pro-GRP,NSE,CYFRA21-1,SCC-Ag,CEA). METHODS: The predictive capacity of serum biomarkers was evaluated to discriminate between lung cancer and benign pathology. The accuracy was also assessed for distinguishing between SCLC and NSCLC and explored their ability to perform histological subtyping. RESULTS: 93 patients were included, 60 with lung cancer, 33 with benign pathology. Pro-GRP and NSE were elevated in SCLC compared with NSCLC or nonmalignant disease. The most accurate for differentiating between malignant and benign pathology were CEA and CYFRA21-1. Pro-GRP had a poor predictive capacity for distinguishing NSCLC from SCLC. However, combined with CEA and CYFRA21-1, performance improved. For SCLC, the diagnostic capacity of Pro-GRP increased by combining with biomarkers, such as NSE/CYFRA21-1. CONCLUSIONS: Biomarkers lacked the sensitivity and specificity for independent differential diagnosis or histological subtyping. However, the observed patterns in biomarker levels associated with specific histological subtypes suggest potential utility in a multi-biomarker approach or in conjunction with other diagnostic tools. This insight could guide future research to improve diagnostic accuracy and personalized treatment strategies in lung cancer.

Biomarkers are crucial for identifying, managing, and predicting outcomes in lung cancer, though they lack accuracy in differentiating histological subtypes.CEA and CYFRA21-1 were the most accurate biomarkers for distinguishing between malignant and benign pathology.Pro-GRP and NSE levels were elevated in SCLC compared to NSCLC. Pro-GRP alone had poor predictive capacity for differentiating NSCLC from SCLC, but combining it with CEA and CYFRA21-1 improved diagnostic performance.Patterns in biomarker levels suggest that a multi-biomarker approach, especially when combined with other diagnostic tools, could improve diagnostic accuracy.

Molecular profiling and patient selection for the multimodal approaches for patients with resectable colorectal liver metastases.

Colorectal cancer represents the third most common cancer and about 20% are diagnosed with synchronous metastatic disease. From a historical point of view, surgery remains the mainstream treatment for resectable colorectal liver metastases (CRLM). Furthermore, disease outcomes are improving due significant advances in systemic treatments and diagnostic methods. However, the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open question. Thus, patient selection combining image workouts, time of recurrence, positive lymph nodes, and molecular biomarkers can improve the decision-making process. Nevertheless, molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of treatment. Tumor biomakers, genetic profiling, and circulating tumor DNA have been used to offer as much personalized treatment as possible, based on the precision oncology concept of tailored care rather than a guideline-based therapy. This review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.

Hepatitis C virus associated ALT, AST, GGT, Bili T, HB, HBA1C, CREAT, PT, aPPT, AFP, CEA, CA 125, CA 19-9, iPTH biomarkers, computed tomography and HCV burden of disease during pre COVID-19 era (2018-2019) and post COVID-19 era (2020-2022) in Pakistan / ALT, AST, GGT, Bili T, HB, HBA1C, CREAT, PT, aPPT, AFP, CEA, CA 125, CA 125, CA 19-9: biomarcadores iPTH associados ao vírus da hepatite C, tomografia computadorizada e carga de doença do VHC durante a era pré-COVID-19 (2018-2019) e era pós-COVID-19 (2020-2022) no Paquistão

The national burden of HCV has significantly mounted over the period of last few decades placing Pakistan at the worst placement of second largest burden of HCV globally. Herein for the first time from Pakistan, we examined clinical correlation of potential biomarkers with HCV. Nation-wide study was conducted on 13,348 suspected HCV patients during 2018-2022. During pre-COVID-19 era of 2018-2019, prevalence of HCV remained 30%. During 2018, among HCV positive patients, 91% of ALT, 63% of AST, 67% of GGT, 28% of Bili T, 62% of HB, 15% of HBA1C, 25% of CREAT, 15% of PT, 15% of aPTT and 64% of AFP were abnormal. During 2019, among HCV infected 74.47% of ALT, 63.54% of AST, 70.24% of GGT, 24.71% of Bili T, 8.77% of HB and 75% of AFP were raised. CT/CAT scan revealed 4.65% liver complications (mild 13.04%, moderate 30.43% and severe 56.52%). During 2020, HCV prevalence remained 25%. 65.17% of ALT, 64.20% of AST, 68.75% of GGT, 31.25% of Bili T, 20.97% of HB, 4.65% of CREAT and 73.68% of AFP levels were raised. CAT analysis revealed liver complications among 4.41% (14.81% mild, 40.74% moderate, and 44.44% sever). 85.71% of participants diabetes was out of control. During 2021, HCV prevalence remained 27.1%. ALT (73.86%), AST (50.6%), GGT (67.95%), Bili T (28.21%), HB (20%), CREAT (5.8%) and AFP (82.14%) levels were abnormal. During 2022, the levels of ALT (56.06%), AST (56.36%), GGT (56.6%), Bili T (19.23%), HB (43.48%), HBA1C (14.81), CREAT (18.92%), AFP (93.75%) were abnormal. CAT analysis revealed 7.46% liver complications (25% mild, 30.36% moderate, and 42.86% sever). During 2021-2022, 83.33% of subject's diabetes was not controlled.

A carga nacional de HCV aumentou significativamente ao longo das últimas décadas, colocando o Paquistão na pior colocação da segunda maior carga de HCV globalmente. Pela primeira vez no Paquistão, examinamos a correlação clínica de potenciais biomarcadores com HCV. Um estudo nacional foi realizado com 13.348 pacientes suspeitos de HCV de 2018 a 2022. Durante a era pré-COVID-19 de 2018 a 2019, a prevalência do HCV permaneceu em 30%. Durante 2018, entre pacientes positivos para HCV, 91% de ALT, 63% de AST, 67% de GGT, 28% de Bili T, 62% de HB, 15% de HBA1C, 25% de CREAT, 15% de PT, 15% de aPTT e 64% de AFP eram anormais. Durante 2019, entre os infectados pelo HCV, 74,47% de ALT, 63,54% de AST, 70,24% de GGT, 24,71% de Bili T, 8,77% de HB e 75% de AFP foram elevados. A TC/TAC revelou 4,65% de complicações hepáticas (leve 13,04%, moderada 30,43% e grave 56,52%). Durante 2020, a prevalência do HCV permaneceu em 25%. 65,17% de ALT, 64,20% de AST, 68,75% de GGT, 31,25% de Bili T, 20,97% de HB, 4,65% de CREAT e 73,68% de AFP estavam elevados. A análise de TAC revelou complicações hepáticas em 4,41% (14,81% leves, 40,74% moderadas e 44,44% graves). 85,71% dos participantes o diabetes estava fora de controle. Durante 2021, a prevalência de HCV permaneceu em 27,1%. Os níveis de ALT (73,86%), AST (50,6%), GGT (67,95%), Bili T (28,21%), HB (20%), CREAT (5,8%) e AFP (82,14%) estavam anormais. Durante 2022, os níveis de ALT (56,06%), AST (56,36%), GGT (56,6%), Bili T (19,23%), HB (43,48%), HBA1C (14,81), CREAT (18,92%), AFP (93,75%) eram anormais. A análise de TAC revelou 7,46% de complicações hepáticas (25% leves, 30,36% moderadas e 42,86% severas). Durante 2021 e 2022, 83,33% do diabetes do sujeito não foi controlado.

Earlier Diagnosis of Pancreatic Cancer: Is It Possible?

Pancreatic ductal adenocarcinoma has a very high mortality rate which has been only minimally improved in the last 30 years. This high mortality is closely related to late diagnosis, which is usually made when the tumor is large and has extensively infiltrated neighboring tissues or distant metastases are already present. This is a paradoxical situation for a tumor that requires nearly 15 years to develop since the first founding mutation. Response to chemotherapy under such late circumstances is poor, resistance is frequent, and prolongation of survival is almost negligible. Early surgery has been, and still is, the only approach with a slightly better outcome. Unfortunately, the relapse percentage after surgery is still very high. In fact, early surgery clearly requires early diagnosis. Despite all the advances in diagnostic methods, the available tools for improving these results are scarce. Serum tumor markers permit a late diagnosis, but their contribution to an improved therapeutic result is very limited. On the other hand, effective screening methods for high-risk populations have not been fully developed as yet. This paper discusses the difficulties of early diagnosis, evaluates whether the available diagnostic tools are adequate, and proposes some simple and not-so-simple measures to improve it.

Revisiting ab initio carcinoembryonic antigen and CA19-9 tumor markers in colorectal carcinoma in association with anatomotopographic location and staging of disease

SUMMARY OBJECTIVE: This study purposed to evaluate preoperative two tumor markers, namely, carcinoembryonic antigen and carbohydrate antigen (CA)19-9, in colorectal cancer for anatomotopographic location with disease stage and to assess their utility for diagnostic staging purposes. METHODS: The study retrospectively incorporated patients who had undergone surgery for colorectal cancer at our department in 2015-2018 and in whom carcinoembryonic antigen and CA19-9 tumor markers had been preoperatively analyzed. The obtained data were then statistically processed using R-project. RESULTS: A total of 155 patients had been incorporated, of whom 96 (62%) were men and 59 (38%) were women. Rectum was the most common location (74 patients, 48%), and the least represented stage was IV (18, 12%). The marker carcinoembryonic antigen was obtained in all 155 cases, while CA19-9 was in 105. The median carcinoembryonic antigen was 3 (0.34-1104.25), and the median CA19-9 was 12 (0.18-840.00). A significance was recognized between median carcinoembryonic antigen and disease stage (p-value=0.016), with stages I, II, and III (medians 2, 3, and 2) different from stage IV (median 13), while no significance for CA19-9 was recognized (p-value=0.343). No significance between either marker and location (carcinoembryonic antigen: p=0.276; CA19-9: p=0.505) was detected. The testing was performed at a significance level of alpha=0.05. CONCLUSION: This study revealed a significance between the marker carcinoembryonic antigen, but not CA19-9, and the disease stage, while no relationship of either of these markers with tumor location was found. Herewith, the study confirmed that higher carcinoembryonic antigen values may suggest the finding of more advanced forms of colorectal cancer and thus a worse prognosis of this malignant phenomenon.

Co-Expression of Immunohistochemical Markers MRP2, CXCR4, and PD-L1 in Gallbladder Tumors Is Associated with Prolonged Patient Survival.

Gallbladder cancer (GBC) is a rare pathology in Western countries. However, it constitutes a relevant health problem in Asia and Latin America, with a high mortality in middle-aged Chilean women. The limited therapeutic options for GBC require the identification of targetable proteins with prognostic value for improving clinical management support. We evaluated the expression of targetable proteins, including three epithelial tumor markers, four proteins associated with multidrug and apoptosis resistance, and eleven immunological markers in 241 primary gallbladder adenocarcinomas. We investigated correlations between tumor marker expression, the primary tumor staging, and GBC patients' survival using automated immunohistochemistry, a semi-automatic method for image analysis, univariate and multivariate statistical analyses, and machine learning algorithms. Our data show a significant association between the expression of MRP2 (p = 0.0028), CXCR4 (p = 0.0423), and PD-L1 (p = 0.0264), and a better prognosis for patients with late-stage primary tumors. The expression of the MRP2/CXCR4/PD-L1 cluster of markers discriminates among short-, medium-, and long-term patient survival, with an ROC of significant prognostic value (AUC = 0.85, p = 0.0012). Moreover, a high MRP2/CXCR4/PD-L1 co-expression is associated with increased survival time (30 vs. 6 months, p = 0.0025) in GBC patients, regardless of tumor stage. Hence, our results suggest that the MRP2/CXCR4/PD-L1 cluster could potentially be a prognostic marker for GBC.

Cáncer colorrectal ­ diagnóstico y tratamiento: revisión bibliográfica / Colorectal cancer ­ diagnosis and treatment: literature review

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Although improvements in detection and treatment have been implemented; CRC incidence, prevalence, and mortality remain high, even in developed countries. The risk of developing this cancer is related to poor eating habits, smoking, inflammatory bowel disease, polyps, genetic factors, and aging. There are several methods for detecting colorectal cancer, including the guaiac test, stool immunochemical test, stool DNA test, sigmoidoscopy, colonoscopy, and barium enema. The stage at which the cancer is detected determines the patient's prognosis, survival, and treatment. Treatments include endoscopic and surgical local excision, preoperative radiation therapy and systemic downstage therapy, extensive surgery for locoregional and metastatic disease, local ablative therapies for metastases, and palliative, targeted chemotherapy and immunotherapy.

El cáncer colorrectal (CCR) es el tercer cáncer más prevalente a nivel mundial. A pesar de que se han implementado mejoras en la detección y el tratamiento; la incidencia, la prevalencia y la mortalidad del CCR siguen siendo altas, incluso en países desarrollados. El riesgo de desarrollar este cáncer está relacionado con malos hábitos alimentarios, tabaquismo, enfermedad inflamatoria intestinal, pólipos, factores genéticos y envejecimiento. Existen varios métodos para detectar el cáncer colorrectal, como la prueba de guayaco, la prueba inmunoquímica de heces, la prueba de ADN en heces, la sigmoidoscopia, la colonoscopia y el enema de bario. El estadio en el que se detecta el cáncer determina el pronóstico, la supervivencia y el tratamiento del paciente. Los tratamientos incluyen escisión local endoscópica y quirúrgica, radioterapia preoperatoria y terapia sistémica de reducción del estadio, cirugía extensa para enfermedad locorregional y metastásica, terapias ablativas locales para metástasis y quimioterapia paliativa, terapia dirigida e inmunoterapia.

Advances in Intraoperative Flow Cytometry.

Flow cytometry is the gold-standard laser-based technique to measure and analyze fluorescence levels of immunostaining and DNA content in individual cells. It provides a valuable tool to assess cells in the G0/G1, S, and G2/M phases, and those with polyploidy, which holds prognostic significance. Frozen section analysis is the standard intraoperative assessment for tumor margin evaluation and tumor resection. Here, we present flow cytometry as a promising technique for intraoperative tumor analysis in different pathologies, including brain tumors, leptomeningeal dissemination, breast cancer, head and neck cancer, pancreatic tumor, and hepatic cancer. Flow cytometry is a valuable tool that can provide substantial information on tumor analysis and, consequently, maximize cancer treatment and expedite patients' survival.

Influence of high altitude on the expression of HIF-1 and on the prognosis of Ecuadorian patients with gastric adenocarcinoma.

Since the incidence of gastric adenocarcinoma (GA) is high in populations living at high altitudes, we evaluated the influence of altitude on the expression of HIF-1 and survival of Ecuadorian GA patients. METHOD: 155 GA cases were studied: 56 from coastal (GAC) and 99 from mountainous regions (GAM), and 74 non-GA controls (25 coast and 49 mountain). The expression of HIF-1/HER2 was analyzed by immunohistochemistry. Analyses were performed using Fisher's exact and Breslow-Day tests for homogeneity and Kaplan-Meier curves and restricted median survival time ΔRMST. RESULTS: HIF-1 was overexpressed in normal/inflamed gastric mucosa, especially in mountainous non-GA patients (p = 0.001). There was no difference between GAC and GAM in terms of age/gender, HIF-1/HER2 expression, stage/tumor location. Median survival at 120 months was significantly higher among GAC, with a difference (ΔRMST) of 43.7 months (95% CI 29.5, 57.8) (p < 0.001) and those with positive HIF-1 expression: ΔRMST 26.6 months (95% CI 11.0, 42.1) (p < 0.001). Positive HIF-1 expression was associated with better GAM survival, with ΔRMST 33.6 months (95% CI 14.2, 52.9) (p < 0.001). CONCLUSION: Despite the limitations of this retrospective study, GA patients in the coastal region and those who expressed HIF-1 exhibited a better prognosis, but this factor was associated with better survival only in the mountain region.

Síndrome de teratoma creciente. Reporte de caso / Growing Teratoma Syndrome. A Case Report

Resumen El síndrome de teratoma creciente es una entidad en la cual existen modificaciones histológicas de un teratoma maligno inmaduro tratado con quimioterapia y con marcadores tumorales negativos a un teratoma maduro. Dada la baja incidencia de la patología, se presenta el caso de una paciente con antecedente de tumoración ovárica con reporte de teratoma inmaduro la cual fue extraída. Recibió quimioterapia y normalización de marcadores séricos. Posteriormente presentó la aparición de una tumoración pélvica, retroperitoneal y hepática que nuevamente requirió intervención quirúrgica, con reporte patológico de teratoma quístico maduro.

Abstract Growing teratoma syndrome is an entity in which there are histological modifications of an immature malignant teratoma treated with chemotherapy and with negative tumor markers to a mature teratoma. Given the low incidence of the pathology, a case of a patient with a history of ovarian tumors with report of immature teratoma which was extracted is reported. The patient received chemotherapy with normalization of serum markers. Subsequently she presented a pelvic, retroperitoneal and hepatic tumor that again required surgical intervention with pathological report of mature cystic teratoma.

Factors Associated with Time to Progression and Overall Survival in Patients with De Novo Metastatic Breast Cancer: A Colombian Cohort.

PURPOSE: About 10% of breast cancer (BC) is diagnosed in stage IV. This study sought to identify factors associated with time to progression (TTP) and overall survival (OS) in a cohort of patients diagnosed with de novo metastatic breast cancer (MBC), from a single cancer center in Colombia, given that information on this aspect is limited. METHODOLOGY: An observational, analytical, and retrospective cohort study was carried out. Time to progression and OS rates were estimated using the Kaplan-Meier survival functions. Cox models were developed to assess association between time to progression and time to death, using a group of fixed variables. RESULTS: Overall, 175 patients were included in the study; 33.7% of patients had luminal B HER2-negative tumors, 49.7% had bone involvement, and 83.4% had multiple metastatic sites. Tumor biology and primary tumor surgery were the variables associated with TTP and OS. Patients with luminal A tumors had the lowest progression and mortality rates (10 per 100 patients/year (95% CI: 5.0-20.0) and 12.6 per 100 patients/year (95% CI: 6.9-22.7), respectively), and patients with triple-negative tumors had the highest progression and mortality rates (40 per 100 patients/year (95% CI: 23.2-68.8) and 44.1 per 100 patients/year (95% CI: 28.1-69.1), respectively). Across the cohort, the median TTP was 2.1 years (95% CI: 1.6; the upper limit cannot be reached) and the median OS was 2.4 years (95% CI: 2-4.3). CONCLUSIONS: In this cohort, patients with luminal A tumors and those who underwent tumor surgery given that they presented clinical benefit (CB) after initial systemic treatment, had the lowest progression and mortality rates. Overall, OS was inferior to other series due to high tumor burden and difficulties in accessing and continuing oncological treatments.

Evaluation of HPV and EBV in OSCC and the expression of p53, p16, E-cadherin, COX-2, MYC, and MLH1.

OBJECTIVE: This study aimed to evaluate the presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) and the expression of p53, p16, E-cadherin, COX-2, MLH1, and MYC in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: One hundred OSCC specimens were submitted to in situ hybridization for HPV and EBV, and immunohistochemistry for detection of the human proteins. RESULTS: Thirty-one cases showed HPV in tumor tissue. EBV was not detected in any case investigated. The HPV(+) group demonstrated an increase of staining scores for nuclear p16 (p = .047), cytoplasmic MYC (p = .002), while a decrease for nuclear MLH1 (p = .048), suggesting that HPV may upregulate the expression of the first two proteins and down-regulate the latter. CONCLUSION: Our findings reinforce the hypothesis of the HPV-related oral carcinogenesis involving the expression of p16 and MYC, and MLH1 suppression. Exclusively cytoplasmic stainings for p16, MLH1, and MYC were also associated with more advanced tumors. Finally, in view of the lack of studies correlating the HPV or EBV infection to the expression of oncoproteins, more researches assessing a broader panel of markers and employing different approaches are still necessary in order to understand the role of these viruses as well as the molecular mechanisms involved in the development and progression of oral carcinomas.

Tumor de colisión en el ovario, con fibrotecoma. Reporte de un caso / Collision tumor in the ovary, with fibrothecoma. Case report

Resumen ANTECEDENTES: La coincidencia temporo-espacial de dos o más neoplasias benignas, malignas o combinadas, que afectan a un mismo órgano o tejido es lo que define al tumor de colisión, con diferencias conductuales, genéticas e histológicas. Los tumores de colisión ovárica son un subtipo raro. CASO CLÍNICO: Paciente de 53 años, que acudió al servicio de Urgencias debido a un dolor intermitente de siete meses de evolución que, en las últimas semanas, se intensificó y se agregaron náuseas y vómitos. Durante la exploración abdominal se detectó un aumento de volumen en el área pélvica, sin irritación peritoneal. Los marcadores tumorales: CA-125, CA 19-9 y antígeno carcinoembrionario se reportaron en parámetros normales. La ecografía pélvica informó la existencia de una imagen quística simple y compleja, con componente sólido. El examen de anatomía patológica diagnosticó: tumor de colisión en el ovario izquierdo. CONCLUSION: Los tumores de colisión en el ovario son poco frecuentes según lo reportado en la bibliografía. El diagnóstico anatomopatológico minucioso y el seguimiento clínico-radiológico adecuado son necesarios para descartar los tumores de colisión.

Abstract BACKGROUND: The temporal-spatial coincidence of two or more benign, malignant or combined neoplasms that affect the same organ or tissue is what defines the collision tumor, with behavioral, genetic and histological differences. Ovarian collision tumors are a rare subtype. CLINICAL CASE: A 53-year-old patient, who came to the Emergency Department due to intermittent pain of seven months' evolution, which, in recent weeks, intensified and nausea and vomiting were added. During abdominal examination, an increase in volume was detected in the pelvic area, without peritoneal irritation. Tumor markers: CA-125, CA 19-9 and carcinoembryonic antigen were reported in normal parameters. Pelvic ultrasound reported the existence of a simple and complex cystic image, with a solid component. Pathological anatomy examination diagnosed: collision tumor in the left ovary. CONCLUSION: Collision tumors in the ovary are rare according to reports in the literature. A thorough pathological diagnosis and adequate clinical-radiological follow-up are necessary to rule out colliding tumors.

Self-collected versus clinician-collected cervical samples for the detection of HPV infections by 14-type DNA and 7-type mRNA tests.

BACKGROUND: HPV self-sampling has been widely supported by the scientific community following a strong body of literature on the subject. Self-sampling is important in cervical cancer screening as it has been shown to improve participation. It is well documented that HPV-testing has proven superior to cytology with regards to sensitivity in detection of CIN and cancer. The value of self-collected samples is reliant on the quality of the molecular testing performed, as well as the patients' preference in sampling procedure and compliance to follow up on positive test results. Due to the incompatibility of self-samples and cytology, triage of HPV-DNA positives by testing for molecular biomarkers is highly warranted. METHODS: Our objective was to compare the detection rate of genital Human Papillomavirus (HPV) infection in self- and clinician-collected samples by a 14-type HPV-DNA test and a 7-type mRNA E6/E7 test. RESULTS: Five hundred five women were recruited. Each study participant had two sample collection procedures performed upon the same visit, alternating order in execution of the self-collection or the clinician-taken procedure first or second, 1010 samples in total. HPV-DNA prevalence was 22.8% in self-collected versus 19.2% in clinician-collected samples (P = 0.19). Overexpression of mRNA E6/E7 from 7 HPV types was 7.1 and 6.3%, respectively (P = 0.71). The difference between HPV-DNA and HPV-mRNA positivity rates were statistically significant in both self-collected (22.8% versus 7.1%, P < 0.001) and clinician-collected samples (19.2% versus 6.3%, P < 0.001). Overall agreement between the two collection methods was fair, with a concordance rate of 78.2% (390/505), k = 0.34 (95% CI: 0.25-0.44), P < 0.001, for the HPV-DNA test and 92.5% (467/505), k = 0.40 (95% CI, 0.25-0.56), P < 0.001, for the mRNA test, respectively. 96.8% of the participants reported they felt confident carrying out the self-collection themselves, and 88.8% reported no discomfort at all performing the procedure. CONCLUSIONS: This comparative study of two sampling methods reports fair agreement of HPV positivity rates between the self-collected and clinician-collected specimens using Abbott hrHPV and PreTect HPV-Proofer'7 tests. Only one third of HPV-DNA positive women had overexpression of mRNA E6/E7. TRIAL REGISTRATION: ISRCTN77337300 .

Association of Carcinoembryonic Antigen Reduction With Progression-free and Overall Survival Improvement in Advanced Non-small-cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer elevates serum carcinoembryonic antigen (CEA). CEA determinations are not recommended currently. This study aims to identify the correlation between reducing serum CEA levels with progression-free survival (PFS) and overall survival. METHODS: This study assessed at baseline and in every scheduled visit serum CEA levels throughout first-line therapy. A sensitivity and specificity analysis identified the best cut-off point and correlated it with progression-free survival and overall survival. Multivariate Cox proportional hazard models were conducted. RESULTS: We assessed 748 patients with elevated serum CEA levels at diagnosis. A ≥20% decrease from baseline was associated with a 2-fold median survival compared with patients with lower decreases (20.5 months vs 9.1 months; hazard ratio, 0.53; 95% confidence interval, 0.44 to -0.64; P < .001). CEA sensitivity and specificity to predict survival was 79.8% and 59.8%, respectively. A ≥10% decrease in CEA concentrations was associated with longer progression-free survival (7.7 months vs 5.9 months; hazard ratio, 0.71; 95% confidence interval, 0.57 to -0.88; P = .001) in those treated with chemotherapy, and in patients under tyrosine kinase inhibitors (11.9 months vs 7.3 months; hazard ratio, 0.63; 95% confidence interval, 0.47 to -0.83; P = .0001) and a ≥20% decrease. CONCLUSION: In patients with metastatic non-small cell lung cancer with an elevated baseline CEA level, the percentage decrease of CEA concentrations above the threshold during the first-line therapy was associated with more prolonged survival and progression-free intervals. Serum CEA determinations are a feasible, noninvasive option for monitoring and prognosis.

Decoding the heterogeneous landscape in the development prostate cancer.

Prostate cancer (PCa) is characterized as being histologically and molecularly heterogeneous; however, this is not only incorrect among individuals, but also at the multiple foci level, which originates in the prostate gland itself. The reasons for such heterogeneity have not been fully elucidated; however, understanding these may be crucial in determining the course of the disease. PCa is characterized by a complex network of chromosomal rearrangements, which simultaneously deregulate multiple genes; this could explain the appearance of exclusive events associated with molecular subtypes, which have been extensively investigated to establish clinical management and the development of therapies targeted to this type of cancer. From a clinical aspect, the prognosis of the patient has focused on the characteristics of the index lesion (the largest focus in PCa); however, a significant percentage of patients (11%) also exhibit an aggressive secondary foci, which may determine the prognosis of the disease, and could be the determining factor of why, in different studies, the classification of the subtypes does not have an association with prognosis. Due to the aforementioned reasons, the analysis of molecular subtypes in several foci, from the same individual could assist in determining the association between clinical evolution and management of patients with PCa. Castration-resistant PCa (CRPC) has the worst prognosis and develops following androgen ablation therapy. Currently, there are two models to explain the development of CRPC: i) The selection model and ii) the adaptation model; both of which, have been found to include alterations described in the molecular subtypes, such as Enhancer of zeste 2 polycomb repressive complex 2 subunit overexpression, isocitrate dehydrogenase (NAPD+)1 and forkhead box A1 mutations, suggesting that the presence of specific molecular alterations could predict the development of CRPC. This type of analysis could lead to a biological understanding of PCa, to develop personalized medicine strategies, which could improve the response to treatment thus, avoiding the development of resistance. Therefore, the present review discusses the primary molecular factors, to which variable heterogeneity in PCa progress has been attributed.

Carcinosarcoma de ovario en paciente perimenopáusica / Ovarian carcinosarcoma in a perimenopausal woman

Resumen ANTECEDENTES: El carcinosarcoma de ovario, o tumor mixto de Müller, es una neoplasia infrecuente que representa alrededor del 1 al 4% de los carcinomas ováricos epiteliales. Su histología combina componentes sarcomatosos y carcinomatosos. CASO CLÍNICO: Paciente de 55 años, con diagnóstico de carcinosarcoma de ovario. Acudió a consulta debido a un sangrado uterino irregular y dolor abdominal. En la ecografía transvaginal se encontró una formación anexial sólida y heterogénea de 11.95 x 10.6 cm, con captación Doppler. El estudio se amplió con una tomografía axial computada (TAC) abdominopélvica y de tórax en la que se observó una tumoración en el lado izquierdo de 18 x 13 cm. Los marcadores tumorales se reportaron elevados: CEA 10.60, CA 125 91.3 y CA19.9 153 U/mL, con proteína HE-4 86.8 pmol/L, ligeramente disminuida. La laparotomía exploradora se completó con una cirugía para eliminar toda la carga tumoral. Se indicó quimioterapia con paclitaxel-carboplatino. El estudio histológico definitivo informó la existencia de una tumoración sólida-quística, compatible con un carcinosarcoma en el ovario izquierdo, con amplia diseminación peritoneal. A los 3 meses de la intervención, la paciente continuaba sin signos de recidiva. CONCLUSIONES: El carcinosarcoma es un tumor ginecológico poco frecuente pero muy agresivo; por su excepcional hallazgo aún no se dispone de criterios de tratamiento. Es decisivo fomentar investigaciones futuras acerca de los factores pronósticos y biomarcadores y desarrollar tratamientos dirigidos a las características moleculares de cada paciente.

Abstract BACKGROUND: Ovarian carcinosarcoma, or mixed Müllerian tumor, is a rare neoplasm that represents about 1 to 4% of epithelial ovarian carcinomas. Its histology combines sarcomatous and carcinomatous components. CLINICAL CASE: 55-year-old female patient with a diagnosis of ovarian carcinosarcoma. She consulted due to irregular uterine bleeding and abdominal pain. Transvaginal ultrasound showed a solid and heterogeneous adnexal formation measuring 11.95 x 10.6 cm, with Doppler uptake. The study was expanded with an abdominopelvic and chest computed axial tomography (CT) scan in which a tumor was observed on the left side measuring 18 x 13 cm. Tumor markers were reported elevated: CEA 10.60, CA 125 91.3 and CA19.9 153 U/mL, with HE-4 protein 86.8 pmol/L, slightly decreased. Exploratory laparotomy was completed with R0 surgery. Chemotherapy with paclitaxel-carboplatin was indicated. The definitive histological study reported the existence of a solid-cystic tumor, compatible with a carcinosarcoma in the left ovary, with extensive peritoneal dissemination. Three months after surgery, the patient continued without signs of recurrence. CONCLUSIONS: Carcinosarcoma is a rare but very aggressive gynecologic tumor; because of its exceptional finding no treatment criteria are yet available. It is crucial to encourage future research on prognostic factors and biomarkers and to develop treatments targeted to the molecular characteristics of each patient.

Perfil inmunohistoquímico del mixoma odontogénico, con énfasis en marcadores de agresividad tumoral y microdensidad vascular / Perfil imuno-histoquímico do mixoma odontogênico, com ênfase em marcadores de agressividade tumoral e microdensidade vascular / Immunohistochemical profile of odontogenic myxoma, with a focus on microvascular density and tumor aggressiveness markers

Con el fin de tener una mayor comprensión sobre el comportamiento biológico del mixoma odontogénico (MO), se realizó inmunohistoquímica en 31 muestras, utilizando marcadores relacionados con mecanismos de progresión tumoral (adhesión, angiogénesis, apoptosis, inflamación y proliferación celular). El epitelio odontogénico fue detectado en cuatro muestras mediante CK19 y CD138, este último, mostró expresión baja en matriz extracelular (MEC) y alta en las células tumorales. La microdensidad vascular (MDV) media fue de 7.51 y 5.35 vasos marcados con CD34 y VEGF-A respectivamente. Una alta expresión de Orosomucoide-1 y Mast Cell Tryptase se observó células tumorales y en MEC. El MO mostró negatividad para Calretinina. Este perfil inmunohistoquímico, la baja expresión para Ki-67, Bcl-2 y p53, y la relativamente baja MDV, sugieren que la actividad proliferativa, anti-apoptótica o angiogénica no representan los principales mecanismos de crecimiento del MO, los cuales podrían estar asociados a eventos como inmunomodulación y degradación de la MEC.

Immunohistochemistry tests were performed in 31 samples to elucidate the biological behavior of the odontogenic myxoma (OM), using markers related to mechanisms of tumor progression (adhesion, angiogenesis, apoptosis, inflammation and cell proliferation). Odontogenic epithelium was detected in four samples with CK19 and CD138; the latter had a low expression in the extracellular matrix (ECM) and a high expression in tumor cells. The mean microvascular density (MVD), assessed with CD34 and VEGF-A, was 7.51 and 5.35 blood vessels. A high expression of orosomucoid-1 and mast cell tryptase was observed in tumor cells and ECM, while calretinin was negative. The immunohistochemical profile mentioned above, as well as the low expression of Ki67, Bcl-2 and p53 and the relatively low MVD, suggest that the proliferative, antiapoptotic and angiogenic activities do not represent the main growing mechanisms of OM, which could be associated to other events, such as immunomodulation and ECM degradation.

Para melhor compreensão do comportamento biológico do mixoma odontogênico (MO), imuno-histoquímica foi realizada em 31 amostras, utilizando marcadores relacionados aos mecanismos de progressão tumoral (adesão, angiogênese, apoptose, inflamação e proliferação celular). Epitélio odontogênico foi detectado em quatro amostras por CK19 e CD138, o último mostrou baixa expressão na matriz extracelular (MEC) e alta em células tumorais. A microdensidade vascular (MDV) média foi de 7.51 e 5.35 vasos marcados com CD34 e VEGF-A, respectivamente. Uma alta expressão de Orosomucoide-1 e Mast Cell Tryptase foi observada nas células tumorais e na MEC. O MO mostrou negatividade para Calretinina. O perfil imuno-histoquímico mencionado acima, a baixa expressão de Ki-67, Bcl-2 e p53 e a relativamente baixa MDV, sugerem que a atividade proliferativa, anti-apoptótica ou angiogênica não representam os principais mecanismos de crescimento do MO, os quais poderiam estar associados com eventos como imunomodulação e degradação da MEC.