RESUMEN
BACKGROUND: The poor prognosis of hepatocellular carcinoma (HCC) and the lack of specific screening markers underline the need for new biomarkers for human hepatocarcinogenesis. MATERIALS AND METHODS: We investigated 10 postulated biomarkers for HCC (AFP, GPC3, OPN, IGF1, HGF, SPINK1, KPNA, FUCA1, CgA, HSP90) with microarray gene expression analysis and real-time polymerase chain reaction (RT-PCR) in HCC tissues of different etiologies. RESULTS: Four candidate genes (FUCA1, HGF, IGF1, CgA) showed low median fold changes (fc) of expression compared to corresponding non-malignant liver tissues (fc range=0.2-0.8; maximum 15% of samples). The classic biomarker, alpha-fetoprotein (AFP), was significantly over-expressed (fc=2.4) in 30% of tumors. High tumor AFP expression was associated with significantly elevated serum AFP concentrations (>90% of cases). Five genes (OPN, SPINK1, GPC3, HSP90, KNPA2) showed significantly higher expression than AFP in 64% to 82% of samples (median fc range=2.9-8.3). RT-PCR analyses gave similar results. CONCLUSION: Unlike previous studies, our results did not confirm FUCA1, HGF, IGF1 or CgA as potential markers for HCC. In contrast, OPN, SPINK1, GPC3 and KNPA2 were significantly over-expressed in HCC tissues. These genes may be useful in developing future biomarkers and therapeutic strategies for HCC.
Asunto(s)
Carcinoma Hepatocelular/genética , Proteínas Portadoras/biosíntesis , Glipicanos/biosíntesis , Neoplasias Hepáticas/genética , Osteopontina/biosíntesis , alfa Carioferinas/biosíntesis , Biomarcadores de Tumor/biosíntesis , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , Proteínas de Neoplasias/biosíntesis , Pronóstico , Inhibidor de Tripsina Pancreática de Kazal , alfa-Fetoproteínas/biosíntesisRESUMEN
BACKGROUND: The molecular pathomechanisms leading to hepatitis C virus (HCV)-induced hepatocarcinogenesis remain unclear. This study investigated the molecular pathways and key genes underlying HCV-positive hepatocellular carcinoma (HCC) using gene expression profiling. METHODS: Oligonucleotide arrays (Affymetrix HU133A) were used to determine and compare the tissue-specific gene expression profiles in 39 cases of HCV-positive or -negative HCC and non-malignant liver tissue. The expression values of the most overexpressed genes were validated by real-time polymerase chain reaction (RT-PCR). RESULTS: 837 genes or expressed sequence tags (ESTs) were significantly differently expressed in HCV-positive HCC versus healthy tissue: 414 were upregulated and 423 were downregulated (p < 0.05; > 2-fold change in ≥ 70% of the samples). A specific gene expression profile for HCV-positive HCC was obtained using 2-dimensional cluster analysis and was confirmed using supervised neuronal network modeling. The most consistently overexpressed gene coded for serine protease inhibitor Kazal-type 1 (SPINK1)/tumor-associated trypsin inhibitor (TATI) (median fold change, 19.7; significantly overexpressed in 90% of the samples). SPINK1/TATI was coregulated with matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of metalloproteinases (TIMPs)). CONCLUSIONS: Gene expression profiling identified specific dysregulated molecular pathways and SPINK1/TATI as the most overexpressed gene in HCV-positive HCC. These data highlight the importance of SPINK1/TATI as a tumor marker for HCV-induced HCC and may lead to a better understanding of HCV-induced hepatocarcinogenesis.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/virología , Proteínas Portadoras/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Hepacivirus/genética , Neoplasias Hepáticas/virología , Inhibidor de Tripsina Pancreática de Kazal/genética , Carcinoma Hepatocelular/genética , Perfilación de la Expresión Génica/métodos , Humanos , Neoplasias Hepáticas/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: The low incidence and the variable presentation complicate clinical investigations on biliary tract cancer. The results of Valle et al. in 2009 provided, for the first time, an evidence-based palliative treatment for this rare tumor type. So far no data are available in Germany regarding the current daily care practice. METHODS: We started this national survey in May 2011, including about 3,400 members of the AIO (Working Group Medical Oncology), DGHO (German Society of Hematology and Oncology) and GGHBB (Society of Gastroenterology and Hepatology in Berlin and Brandenburg). The standardized online form contained questions concerning field of action and diagnostic and therapeutic procedures. Evaluation was conducted anonymously. RESULTS: 162 responses could be obtained, corresponding to a response rate of about 5%. 70.4% of the respondents were physicians in hospitals, 23.5% stated to work in private practices. 61.7% of the respondents were medical oncologists and 27.2% gastroenterologists. 52.5% of the participants pointed out to use the standard regimen of gemcitabine and cisplatin. For second-line regimen, the most frequent answer (29%) specified the administration of oxaliplatin in combination with 5-fluorouracil (5-FU) or capecitabine. CONCLUSIONS: This survey may help to clarify the current oncologic daily care procedures for patients with biliary tract cancer in Germany. The results can be helpful for further clinical investigations or the implementation of a tumor-specific register.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/terapia , Endoscopía/estadística & datos numéricos , Oncología Médica/estadística & datos numéricos , Cuidados Paliativos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/epidemiología , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Alemania/epidemiología , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Resultado del Tratamiento , Adulto Joven , GemcitabinaRESUMEN
AIM: The aim of this study was to evaluate survival rates and treatment response in stage I-IV gastric cancer in relation to tumor stage (TNM), histology, Lauren's classification and tumor localization. PATIENTS AND METHODS: Clinical and histopathological data of 160 patients with stage I-IV gastric cancer were analyzed in this retrospective, single-center study. RESULTS: Most patients (73.1%) showed an advanced or metastatic tumor stage (III/IV). The median 3-year overall survival (OS) was 20 ± 16.8 months and correlated significantly with tumor stage (I: OS 30.6 ± 15 months vs. IV: 10.4 ± 9.3 months; p < 0.0001). Stage III/IV tumors were significantly more often poorly differentiated (G3; p = 0.011) and located in the corpus region. Signet ring cell (SRC) cancers were found in a larger proportion of these tumors when compared with locally limited gastric cancers (43.1% vs. 16.3%; p = 0.002). SRC tumors occurred predominantly in women and younger patients and histology was significantly more often of the diffuse subtype according to Lauren (7.5% vs. 63.2%; p < 0.0001) and poorly differentiated (G3 in 95% vs. 73%; p = 0.001). CONCLUSIONS: SRC gastric cancer correlates with poor histopathological criteria and poor prognosis when compared with other histological subtypes. These observations underline the need for more effective treatment in addition to standard approaches.
Asunto(s)
Carcinoma de Células en Anillo de Sello/diagnóstico , Carcinoma de Células en Anillo de Sello/mortalidad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Anciano , Femenino , Alemania/epidemiología , Humanos , Masculino , Prevalencia , Pronóstico , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. METHODS: The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky >or=60%/Child-Pugh Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico
, Inductores de Interferón/uso terapéutico
, Neoplasias Hepáticas/tratamiento farmacológico
, Extractos del Timo/uso terapéutico
, Adolescente
, Adulto
, Anciano
, Anciano de 80 o más Años
, Carcinoma Hepatocelular/secundario
, Progresión de la Enfermedad
, Método Doble Ciego
, Femenino
, Estudios de Seguimiento
, Humanos
, Neoplasias Hepáticas/patología
, Masculino
, Persona de Mediana Edad
, Estadificación de Neoplasias
, Cuidados Paliativos
, Placebos
, Estudios Prospectivos
, Tasa de Supervivencia
, Resultado del Tratamiento
, Adulto Joven
RESUMEN
BACKGROUND: The aim of the study was to estimate the effect of viral factors (HBV genotype, viral load and kinetics) to treatment response in chronic hepatitis B (CHB) and first-line therapy with adefovir dipivoxil (ADV). METHODS: Sixty-six patients (60% males, 65% HBeAg negative) were treated with 10 mg ADV QD. Quantitative HBV DNA and ALT levels were determined at weeks 4, 12, 24, 48, 72 and 96. Nonresponse or viral resistance to ADV was assessed in patients with either persistent elevated HBV DNA levels (week 24) or with an increase in HBV DNA of at least 1 log after initial decline. RESULTS: Most patients were infected with genotype D (66.7%; genotype A: 27.3%; genotype E: 6%); 86.4% achieved a virological (VR) and 54.5% a biochemical response (BR) in week 48, more often in patients with genotype A (P < 0.01). In week 96, BR increased to 60.5%, whereas a negative HBV DNA was observed in 83.3%. In 3% an ADV-induced viral resistance was detected. As an important predictive parameter for VR, a rapid decline of viral load at week 12 was observed. Of the patients with a negative PCR or drop of viral load of at least 3 log, 96% were still HBV DNA negative at the end of week 96; 77% of patients with a partial response achieved a VR. In contrast, no patient with nonresponse (week 12) reached a negative PCR at week 96 (P < 0.0001). CONCLUSIONS: These results underline the importance of early viral kinetics to assess treatment response in CHB. In ADV nonresponders (week 12), an advanced antiviral therapy or switch to another nucleoside analogue should be considered.
Asunto(s)
Adenina/análogos & derivados , Antivirales/uso terapéutico , ADN Viral/sangre , Hepatitis B Crónica/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Adulto , Alanina Transaminasa/sangre , Farmacorresistencia Viral/efectos de los fármacos , Femenino , Genotipo , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/genética , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Carga ViralRESUMEN
BACKGROUND AND AIM: Thyroid disorders represent a common side effect of antiviral therapy in patients with chronic hepatitis C (CHC). However, there is strong evidence for a higher prevalence of thyroidal antibodies (TA) and nonorgan-specific autoantibodies (NOSA) even before interferon (IFN) administration. Here, we report for the first time on the distribution and occurrence of TA and NOSA before, during, and after treatment with daily highdosed IFN alfacon-1 [consensus IFN (CIFN)]. METHODS: Thyrotropin (TSH) levels and antibodies to different autoantigens were analyzed in 217 patients with CHC (29.8% females) who were treated with CIFN induction therapy (27 or 18 mg q.d.). RESULTS: Pretreatment abnormal TSH levels (TSH>3.0 mU/L or <0.4 mU/L) were detected in 15.6% and occurred significantly more often in females (24.6%; P=0.018). TA could be detected only in 2.6%, NOSA in up to 29.9% (47.4% females vs. 24.2% males). During CIFN induction therapy, low TSH levels were detected in 14.1% whereas elevated TSH levels occurred later (week 48) in up to 15.5%, again preferentially in females (42%, P=0.005). In 1.4% of all patients, treatment had to be discontinued because of symptomatic hyperthyroidism. TAs were detected in 10.5% (30.5% females) and NOSA up to 58% during CIFN treatment. CONCLUSIONS: During CIFN induction therapy, alterations in TSH levels and an increased prevalence of TA and NOSA are quite common, especially in females. Clinically relevant symptoms occur, however, only in a small number (1.4%). Thus, treatment with daily and high-dose CIFN does not appear to increase the incidence of (severe) thyroidal or other autoimmune disorders compared with standard IFN in patients with CHC.
Asunto(s)
Antivirales/administración & dosificación , Autoanticuerpos/sangre , Hepatitis C Crónica/tratamiento farmacológico , Interferón Tipo I/administración & dosificación , Enfermedades de la Tiroides/etiología , Glándula Tiroides/inmunología , Antivirales/efectos adversos , Femenino , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/inmunología , Humanos , Hipertiroidismo/etiología , Hipertiroidismo/inmunología , Interferón Tipo I/efectos adversos , Interferón-alfa , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Proteínas Recombinantes , Enfermedades de la Tiroides/inducido químicamente , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/virología , Glándula Tiroides/metabolismo , Glándula Tiroides/virología , Tiroiditis/etiología , Tiroiditis/inmunología , Tirotropina/sangre , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
PURPOSE: This study examined whether the apoptosis-related protein, BAX, or the microsatellite-instability phenotype provide prognostic information in patients with resected colon cancer. METHODS: A total of 371 stage I-III patients that previously underwent radical surgery were included (mean follow-up 51.8 months). BAX expression was examined by immunohistochemical staining; high-frequency microsatellite instability (MSI+) was determined by assessing the specific marker, BAT26, using single-strand conformation polymorphism (SSCP)-based analysis. RESULTS: High BAX expression was found in 66.4% of patients. MSI+ tumors were observed in 14.8% of 344 patients. Univariate analysis showed that unlike MSI, low BAX expression was significantly correlated with poor disease-specific overall survival (OS) in stages I-III (p = 0.04). Multivariate subgroup analyses revealed that unlike MSI, low BAX was an independent predictor for OS in stage II (p = 0.009); however, in stages I or III, BAX or MSI were not independent predictors of OS. CONCLUSIONS: In stage II colon cancer treated with surgery alone, BAX protein expression may be a predictor for prognosis.
Asunto(s)
Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Inestabilidad de Microsatélites , Proteína X Asociada a bcl-2/metabolismo , Anciano , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Estadificación de Neoplasias , Fenotipo , PronósticoRESUMEN
AIM: To investigate the molecular pathways involved in human cholangiocarcinogenesis by gene expression profiling. METHODS: Oligonucleotide arrays (Affymetrix U133A) were used to establish a specific gene expression profile of intrahepatic CCC in comparison to corresponding non-malignant liver tissue. To validate the expression values of the most overexpressed genes, RT-PCR experiments were performed. RESULTS: Five hundred and fifty-two statistically differentially expressed genes/ESTs (221 probes significantly up-regulated, 331 probes down-regulated; P < 0.05; fold change > 2; > or = 70%) were identified. Using these data and two-dimensional cluster analysis, a specific gene expression profile was obtained allowing fast and reproducible differentiation of CCC, which was confirmed by supervised neuronal network modelling. The most consistently overexpressed gene (median fold change 33.5, significantly overexpressed in 100%) encoded osteopontin. Furthermore, an association of various genes with the histopathological grading could be demonstrated. CONCLUSION: A highly specific gene expression profile for intrahepatic CCC was identified, allowing for its fast and reproducible discrimination against non-malignant liver tissue and other liver masses. The most overexpressed gene in intrahepatic CCC was the gene encoding osteopontin. These data may lead to a better understanding of human cholangiocarcinogenesis.
Asunto(s)
Neoplasias de los Conductos Biliares/genética , Colangiocarcinoma/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Osteopontina/genética , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/cirugía , Colangiocarcinoma/cirugía , Cartilla de ADN , Etiquetas de Secuencia Expresada , Perfilación de la Expresión Génica , Humanos , Hígado/patología , Neoplasias Hepáticas/cirugía , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la PolimerasaRESUMEN
Despite new diagnostic and therapeutic strategies (combined radiochemotherapy, EGFR antibody Cetuximab), the prognosis of head and neck squamous cell carcinoma (HNSCC) is still poor and more information regarding prognosis is essential to establish earlier and better treatment options. To elucidate the role of DNA ploidy and cellular proliferation, resected tumors of 48 patients with primary or recurrent HNSCC were analyzed by flow cytometry and in vitro-5-bromodeoxyuridine incorporation (BrdU). The results were compared with histopathological findings such as tumor size, lymph node involvement and tumor differentiation. To assess the influence of intratumoral heterogeneity of these biological parameters, multiple biopsies (>3) were analyzed by flow cytometry and BrdU-incorporation in 12 larger (>4 cm diameter) tumors. BrdU-labeling index (LI%) was significantly higher in aneuploid HNSCC and correlated significantly with poor histologic differentiation of the analyzed tumor tissues (P<0.001). Furthermore, a trend for higher LI% in nodal positive tumors was observed. Aneuploid HNSCC showed significantly more often tissue dedifferentiation (P=0.049) and in most cases an advanced tumor stage, especially in tumors with biclonal cell lines. Lymph node involvement was also seen more often in aneuploid and undifferentiated tumors. As in aneuploid tumors recurrent HNSCC showed in most cases a higher LI% and poor tissue differentiation, but as a result of the small collection of samples there was no correlation between aneuploidy and tumor recurrence. To proof the robustness of the acquired data and to estimate the influence of intratumoral heterogeneity to ploidy and LI% multiple biopsies were analyzed in larger tumors. Using a specific statistical algorithm a secure estimation of ploidy and LI% was possible by a single biopsy in these tumors. These findings indicate aneuploidy and proliferative activity as important findings for malignant progression in HNSCC. An estimation of these biological parameters may be useful for identification of patients with high risk for lymph node involvement or tumor recurrence and pre-treatment can be performed by a single biopsy. As a conclusion, these patients may benefit from more aggressive treatment.
Asunto(s)
Carcinoma de Células Escamosas/genética , ADN de Neoplasias/genética , Neoplasias de Cabeza y Cuello/genética , Ploidias , Adulto , Anciano , Anciano de 80 o más Años , Bromodesoxiuridina , Carcinoma de Células Escamosas/patología , Proliferación Celular , ADN de Neoplasias/análisis , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Fármacos Sensibilizantes a RadiacionesRESUMEN
OBJECTIVE: To assess the toxicity and activity of bolus mitomycin C (MMC) in combination with a 24-hour continuous infusion of 5-fluorouracil (5-FU) in gastric cancer patients who had received at least one prior chemotherapy regimen. PATIENTS AND METHODS: Patients were treated with MMC (10 mg/m(2)) on days 1 and 22, 5-FU (2.6 g/m(2)) as a 24-hour infusion, and folinic acid 500 mg/m(2) weekly for 6 weeks. RESULTS: Thirty-four patients with gastric cancer, 16 after failure of first-line chemotherapy and 18 after failure of at least two prior chemotherapies, were included. In the intent-to-treat analysis, 9 (26.5%) of the 34 patients had a partial response and 10 (29.4%) a disease stabilization (disease control rate 56%). The median time to progression was 3.3 months (CI95: 2.8-3.7), and the median overall survival was 7.2 months (CI95: 5.9-8.4). Grade III/IV thrombocytopenia occurred in 14.7% of patients (n = 5), while the most frequent nonhematological grade III/IV toxicities were mucositis and diarrhea, each affecting 9% of patients. CONCLUSIONS: As the tested regimen was generally safe and well tolerated by the patients, MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen for patients with advanced gastric cancer.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Mitomicina/efectos adversos , Estadificación de Neoplasias , Retratamiento , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de SupervivenciaRESUMEN
PURPOSE: To determine the prognostic impact of BAX in correlation to its upstream effector p53 as well as clinicopathologic variables and patient outcome in preoperatively irradiated rectal carcinoma. METHODS AND MATERIALS: We investigated 92 rectal carcinoma patients treated by preoperative radiotherapy to a total dose of 30 Gy followed by surgery. Median follow-up was 71 months. Immunohistochemistry was performed on paraffin sections of pretreatment biopsy samples for BAX protein. Also, we considered the previously determined p53 expression data from this cohort. RESULTS: BAX protein expression was classified as high and low in 63 (68.5%) and 29 (31.5%) tumors, respectively. Unlike clinicopathologic variables, high BAX expression was significantly associated with improved disease-free survival by univariate analysis (p = 0.048). Moreover, in multivariate analyses, high BAX expression was an independent prognostic indicator for both improved local recurrence-free interval and improved disease-free survival (p = 0.03 and 0.047, respectively). Concerning the p53/BAX pathway, subgroup analysis yielded no association between p53 immunonegative/BAX high vs. p53 immunopositive/BAX low expressing tumors with regard to overall, disease-free, or local recurrence-free survival in either univariate (p = 0.88, 0.54, and 0.16, respectively) or multivariate analysis. CONCLUSIONS: This study demonstrates that BAX protein expression might help to predict disease recurrence in preoperatively irradiated rectal carcinoma, whereas determination of p53, the proposed upstream regulator of BAX-induced apoptosis, did not provide additional prognostic information.
Asunto(s)
Adenocarcinoma/química , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Neoplasias del Recto/química , Adenocarcinoma/mortalidad , Adenocarcinoma/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Neoplasias del Recto/mortalidad , Neoplasias del Recto/radioterapia , Estadística como Asunto , Proteína p53 Supresora de Tumor/análisis , Proteína X Asociada a bcl-2RESUMEN
Surgery remains the only curative treatment option for cholangiocarcinoma (CC). Currently, both early identification of CC in affected individuals at high risk and accurate diagnosis of unexplained biliary strictures are problematic. However, growing insights into biochemical and molecular mechanisms underlying biliary carcinogenesis have suggested serum and bile markers for the diagnosis of CC. These tools include tumor antigens or products (e.g., carbohydrate antigen [CA] 19-9), cytokines (e.g., interleukin-6), metabolic products (e.g., lactate), proteases (e.g., trypsinogen-2), regulatory peptides (e.g., pancreatic polypeptide), and (epi-)genetic lesions (e.g., K- ras and p53 mutations, p16 (INK4a) or p14 (ARF) promoter hypermethylation). In this article we discuss these new potential tumor markers for the diagnosis of CC.