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Martin Werner

Publications and source records attributed to Martin Werner.

At least 37 records · Page 2Linked to original sources
PubMed2004

Giant ancient schwannoma of pancreatic head treated by extended pancreatoduodenectomy.

We report a case of a 55-year-old woman who was transferred from another center to our university clinic after diagnostic laparotomy with a pancreatic head tumor which was seen to encase the portal vein. Although intraoperative biopsies were performed, a histologic diagnosis of the tumor was not possible before giving suspect to a malignant tumor being resectable only with a vascular resection. In a second operation we performed a pylorus-preserving pancreatoduodenectomy. Due to adhesion of the tumor to the portal vein, a segmental resection and end-to-end anastomosis of the portal vein was necessary. Postoperative histologic diagnosis revealed an ancient schwannoma which was removed in toto being a rare report of this benign tumor in the pancreatic head. Ten months after the operation the patient is without any health problems. Partial resection of the portal vein, which is considered to be a safe procedure in high volume centers, stands in contrary to surgical nihilism of pancreatic head tumors suspecting advanced tumors with vascular involvement.

Female↗
PubMed2004

Mutual amplification of apoptosis by statin-induced mitochondrial stress and doxorubicin toxicity in human rhabdomyosarcoma cells.

Besides their cholesterol-lowering effect, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) show antiproliferative behaviour, which has been suggested as a promising anticancer strategy. However, the signalling cascades leading to statin-induced death of cancer cells are poorly characterized. Here we show that statins activate the mitochondrial pathway of apoptosis in rhabdomyosarcoma RD cells via translocation of Bax from the cytosol to mitochondria. The prototypical representative of statins, simvastatin, induced consecutive activation of caspase 9 and 3 in a concentration-dependent manner. The permeability transition pore inhibitor bongkrekic acid was capable of completely preventing simvastatin-induced caspase 9 and 3 activity, corroborating the mitochondrial pathway of apoptosis as the sole mechanism of statin action. Alternative pathways via death receptors, that is, caspase 8 or calpain activation, were not triggered by simvastatin. Simvastatin-treated RD cells could be completely rescued from apoptosis by the co-application of mevalonic acid, indicating that deprivation of cholesterol precursors is essential for statin-induced apoptosis. However, pretreatment with subthreshold concentrations of simvastatin was sufficient to augment doxorubicin toxicity via the mitochondrial apoptotic machinery. Moreover, the presence of doxorubicin increased the potency of simvastatin to trigger caspase activation. Taken together, these data highlight the therapeutic anticancer potential of statins and their additivity and mutual sensitization, in combination with doxorubicin in human rhabdomyosarcoma cells.

Apoptosis↗
PubMed2004

Intragraft iNOS induction during human liver allograft rejection depresses cytochrome p450 activity.

Allograft function may become impaired during rejection after human liver transplantation. Cytokines induce nitric oxide (NO) production in hepatocytes, Kupffer cells and infiltrating mononuclear cells. NO inhibits cytoplasmatic cytochrome p450 (CYP) enzyme activity in vitro. It is not known whether this mechanism plays a role in vivo. In order to characterize the role of locally produced cytokines in the pathogenesis of liver dysfunction, we analysed human liver transplant biopsy material for the expression of proinflammatory cytokines as well as for NO synthase and we compared these results to the microsomal liver function in vivo [aminopyrine breath test (ABT)] and in vitro (enzymatic analysis of CYP). Microsomal liver function decreased in vivo during rejection while ABT levels decreased by 40% and increased again by 59% after the acute rejection episode. Similarly, CYP 1A2 and 2E1 activity dropped 42% and 24% in rejecting samples, respectively. Competitive reverse transcriptase polymerase chain reaction (RT-PCR) showed a fivefold upregulation of interferon gamma (IFN-gamma) gene expression. Inducible, but not constitutive NO-synthase gene expression was upregulated fivefold in samples from rejecting patients suggesting a local induction of NO in response to immune events. Our data show a marked impairment of CYP enzyme activity during allograft rejection which is presumably secondary to an increased intragraft production of proinflammatory cytokines and NO.

Aminopyrine↗
PubMed2004

Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma.

PURPOSE: Maintenance of telomeres through reactivation of telomerase is a prerequisite for tumors to preserve their ability to proliferate. The purpose of this study was to evaluate telomere length and human telomerase reverse transcriptase (hTERT) expression as markers for progression and prognosis of colorectal carcinoma. PATIENTS AND METHODS: Telomere length and hTERT expression were analyzed in matched cancer and adjacent noncancer mucosa samples from 57 patients with R0-resected colorectal carcinoma. The median follow-up time was 76 months. RESULTS: Telomere length and hTERT expression correlated significantly in cancer tissues and adjacent mucosa samples (r = 0.52, P <.001; and r = 0.54, P <.001, respectively). Overall, cancer tissue had shorter telomeres than adjacent mucosa (P <.001). Only in noncancer tissue did telomere length decrease with age (r = 0.36; P <.01). Telomere length in cancer tissue was significantly correlated with tumor stage (P <.01), with longer telomeres in advanced tumors. Patients with ratios of telomere length in cancer to noncancer tissue greater than 0.90 had a significantly poorer overall survival compared with patients with smaller telomere length ratios (P <.002). In multivariate analysis, the telomere length ratio proved to be of independent prognostic value (P <.03). CONCLUSION: Telomeres in colorectal carcinoma tissue were significantly shorter compared with adjacent normal mucosa as an indication for extensive cell proliferation. The correlation with tumor stage and patient survival suggest that hTERT-mediated telomere stabilization may be critical for progression and prognosis of colorectal carcinoma.

Adult↗
PubMed2004

Barrett's esophagus: histopathologic definitions and diagnostic criteria.

Adenocarcinoma of the distal esophagus is rising more rapidly in incidence than any other visceral malignancy in the Western world. It is well established that most, if not all, of these tumors develop in Barrett's esophagus via the metaplasia-dysplasia-carcinoma sequence and could theoretically be detected at an early stage, but despite this, the majority of these tumors are still detected late in their course. This highlights the fact that the goal of effective surveillance for patients at risk for developing an adenocarcinoma of the distal esophagus is still far off. In addition, adenocarcinomas of the esophagogastric junction and gastric cardia are also rising in incidence, but their carcinogenesis and their relation to Barrett's esophagus are still being defined, as are the meaning and significance of the relatively new entities "short-segment Barrett's" and "ultra-short-segment Barrett's". This review attempts to clarify the main histopathologic issues concerned with the definition of Barrett's esophagus, its distinction from intestinal metaplasia of the gastric cardia, as well as the criteria for the histologic diagnosis of dysplasia and carcinoma in Barrett's esophagus.

Adenocarcinoma↗
PubMed2004

Array-based comparative genomic hybridization for the detection of DNA sequence copy number changes in Barrett's adenocarcinoma.

Array-based comparative genomic hybridization (aCGH) allows the identification of DNA sequence copy number changes at high resolution by co-hybridizing differentially labelled test and control DNAs to a micro-array of genomic clones. The present study has analysed a series of 23 formalin-fixed, paraffin wax-embedded tissue samples of Barrett's adenocarcinoma (BCA, n = 18) and non-neoplastic squamous oesophageal (n = 2) and gastric cardia mucosa (n = 3) by aCGH. The micro-arrays used contained 287 genomic targets covering oncogenes, tumour suppressor genes, and DNA sequences localized within chromosomal regions previously reported to be altered in BCA. DNA sequence copy number changes for a panel of approximately 50 genes were identified, most of which have not been previously described in BCA. DNA sequence copy number gains (mean 41 +/- 25/BCA) were more frequent than DNA sequence copy number losses (mean 20 +/- 15/BCA). The highest frequencies for DNA sequence copy number gains were detected for SNRPN (61%); GNLY (44%); NME1 (44%); DDX15, ABCB1 (MDR), ATM, LAMA3, MYBL2, ZNF217, and TNFRSF6B (39% each); and MSH2, TERC, SERPINE1, AFM137XA11, IGF1R, and PTPN1 (33% each). DNA sequence copy number losses were identified for PDGFB (44%); D17S125 (39%); AKT3 (28%); and RASSFI, FHIT, CDKN2A (p16), and SAS (CDK4) (28% each). In all non-neoplastic tissue samples of squamous oesophageal and gastric cardia mucosa, the measured mean ratios were 1.00 (squamous oesophageal mucosa) or 1.01 (gastric mucosa), indicating that no DNA sequence copy number chances were present. For validation, the DNA sequence copy number changes of selected clones (SNRPN, CMYC, HER2, ZNF217) detected by aCGH were confirmed by fluorescence in situ hybridization (FISH). These data show the sensitivity of aCGH for the identification of DNA sequence copy number changes at high resolution in BCA. The newly identified genes may include so far unknown biomarkers in BCA and are therefore a starting point for further studies elucidating their possible role in Barrett's carcinogenesis.

Adenocarcinoma↗
PubMed2004

ERCP or EUS for tissue diagnosis of biliary strictures? A prospective comparative study.

BACKGROUND: The accuracy of ERCP-based brush cytology or forceps biopsy for tissue diagnosis is relatively low (usually not exceeding 70%). By contrast, reported accuracy rates for EUS-guided FNA of pancreatobiliary masses are over 80%. This prospective study compared these two modalities for the first time in the diagnosis of indeterminate biliary strictures and pancreatic tumors. METHODS: Fifty consecutive patients (29 men, 21 women; mean age 62.1 years) with obstructive jaundice in whom a tissue diagnosis was required were included. During ERCP, intraductal specimens were obtained with a forceps and with two different types of brush (conventional and spiral suction) in random order. During EUS, only visible mass lesions or localized bile duct wall thickening were aspirated (22-gauge needle), with at least two passes yielding material sufficient for assessment. A cytopathologist was not present in the procedure room to evaluate specimen adequacy. The reference methods were surgery, other biopsy results, follow-up until death, or the conclusion of the study (mean follow-up 20 months). RESULTS: The final diagnoses were malignancy, 28 (16 pancreatic, 12 biliary), and benign biliary stricture, 22. Sensitivity and specificity for ERCP-guided biopsy were 36% and 100%, respectively; for ERCP-guided cytology (when using conventional and spiral suction brushes), 46% and 100%, respectively; and for EUS-guided FNA, 43% and 100%, respectively. If the punctured lesions are considered (n=28) alone, the sensitivity of EUS-guided FNA was 75%. In general, sensitivity was better for ERCP-based techniques in the subgroup biliary tumor (ERCP 75% vs. EUS 25%), whereas EUS-guided biopsy was superior for pancreatic mass (EUS 60% vs. ERCP 38%). CONCLUSIONS: For biliary strictures, combined ERCP- and EUS-guided tissue acquisition seems to be the best approach to tissue diagnosis. From a clinical standpoint, it appears reasonable, when a tissue diagnosis is required, to start with ERCP if biliary malignancy is suspected and with EUS when a pancreatic tumor is thought to be the cause of a biliary stricture.

Adult↗
PubMed2003

Vascular diffusion density and survival of patients with primary lung carcinomas.

AIM: To investigate the clinical significance of tumour vascularisation in operated lung cancer patients. MATERIALS AND METHODS: Histological slides obtained from 498 patients with potentially curative operated lung carcinomas in two different institutions of thoracic surgery were immunohistochemically stained with an anti-CD34 antibody and subjected to quantitative image analysis. Syntactic structure analysis measured the absolute and relative features of vessels, including the numerical tumour cells densities relative to their nearest neighbouring vessel. These data are associated with tumour volume, post-surgical TNM stage, and each patient's survival. RESULTS: The clinical data, including sex distribution, age of patients, pTNM stages and survival, did not differ between the two institutions. The tumour vascularisation (volume fraction, Vv) amounted to 7% in lung carcinomas, was independent from cell type and increased in advanced tumour stages (pT4, pN3). Advanced tumour stages presented with a higher numerical vascular density and with maintained minimum diameter and circumference of vessels. Each patient's survival was closely associated with the pN stage, tumour volume, cell type and numerical density of tumour cells within a distance less than 20 micro m from the nearest neighbouring vessel due to multivariate statistical analysis. CONCLUSION: Vascularisation of lung tumours becomes altered in advanced tumour stages. Of prognostic significance is the distribution of tumour cells in relation to the nearest neighbouring vessel only.

Adenocarcinoma↗
PubMed2003

Telomere length and hTERT expression in patients with colorectal carcinoma.

The stabilization of telomere length by telomerase activation is an important step in carcinogenesis. Quantification of the catalytic telomerase subunit hTERT (human Telomerase Reverse Transcriptase) is a new indirect measure for telomerase. Telomere length and hTERT expression in cancer tissue and corresponding normal mucosa of 57 patients with completely resected colorectal carcinoma (UICC stage I-IV, R0) were determined for correlation with histopathological parameters and survival. Telomere lengths were measured using Southern Blot and hTERT-encoding mRNA was quantified by real-time RT-PCR. Telomere length and hTERT expression were significantly correlated in normal mucosa and cancer tissue (p<0.001). Telomere length and hTERT expression decreased with ageing only in normal mucosa. Cancer tissue had significantly shorter telomeres (p<0.001) and significantly lower hTERT expression levels (p<0.001) than corresponding normal mucosa. UICC stage I tumors showed significantly shorter telomeres than UICC stage II-IV tumors (p<0.002). Telomere length and hTERT expression were significantly correlated with overall survival. Telomere length and hTERT expression play an important role in ageing and carcinogenesis. Both parameters were identified as prognostic factors in patients with colorectal carcinoma.

Blotting, Southern↗
PubMed2003

Irradiation for conjunctival granulocytic sarcoma.

CASE HISTORY AND FINDINGS: A 73-year-old woman with a history of myeloproliferative syndrome (MPS) presented with bilateral chemosis, redness and burning of the eyes. The ocular motility was severely impaired. Ophthalmological examination revealed markedly distended conjunctivas on both sides. Biopsy disclosed conjunctival granulocytic sarcoma as an initial symptom of acute myelogenous leukemia (AML). Diagnosis was confirmed by peripheral blood smear and bone marrow aspiration. TREATMENT AND OUTCOME: The orbital tumor disappeared completely after local external beam irradiation with a total dose of 30 Gy and no further orbital recurrence occurred. With chemotherapy following irradiation transient hematological remission was achieved. 5 months after diagnosis the patient died of respiratory failure following atypical pneumonia as a consequence of her underlying disorder. CONCLUSION: Detection of orbital granulocytic sarcoma, even in the absence of typical leukemic symptoms is of practical importance, because treatment with irradiation can lead to stabilization or improvement in the patient's vision.

Aged↗
PubMed2003

Distinct chromosomal imbalances in nonpolypoid and polypoid colorectal adenomas indicate different genetic pathways in the development of colorectal neoplasms.

Cytogenetic changes are widely unknown for nonpolypoid (synonymously termed as "flat" or "depressed") colorectal adenomas. A comparison with polypoid adenomas will contribute to the discussion whether different genetic pathways for colorectal tumorigenesis depending on its origin from nonpolypoid or polypoid adenomas exist. Tissue samples of nonpolypoid (n = 22), polypoid (n = 28) adenomas, carcinomas ex-nonpolypoid adenomas (n = 9), carcinomas ex-polypoid adenomas (n = 14), and normal colonic mucosa (n = 9) were investigated by comparative genomic hybridization of whole genomic DNA. Chromosomal imbalances were detected from average comparative genomic hybridization profiles for each entity. Nonpolypoid adenomas show recurrent chromosomal losses on chromosomes 16, 17p, 18, 20, and 22 and gains on chromosomes 2q, 4q, 5, 6, 8q, 12q, and 13q. In polypoid adenomas losses of whole chromosomes 16, 18, and 22 and gains of chromosomes 7q and 13 were detected. The frequency of copy number changes was higher in nonpolypoid compared to polypoid adenomas and early onset of chromosomal changes became apparent in low-grade dysplasias of nonpolypoid adenomas. Gains on chromosomes 2q, 5, 6, 8q, and 12q and losses on chromosomes 17p and 20 occurred exclusively in nonpolypoid adenomas, whereas 16p deletions are significantly more frequent in nonpolypoid than in polypoid adenomas. Carcinomas ex-nonpolypoid adenomas are characterized by more complex aberration patterns compared to nonpolypoid adenomas exhibiting frequent losses on chromosomes 8p, 12q, 14, 15q, 16, 17p, 18, and 22 and gains on 3q, 5, 6, 7, 8q, 12q, and 13, respectively. Normal colonic mucosa showed no chromosomal imbalances. Distinct differences of chromosomal imbalances between nonpolypoid and polypoid colorectal adenomas have been characterized that support the hypothesis that different genetic pathways may exist in the development of colorectal adenomas exhibiting nonpolypoid and polypoid phenotype.

Adenoma↗
PubMed2003

Macromolecular contrast medium (feruglose) versus small molecular contrast medium (gadopentetate) enhanced magnetic resonance imaging: differentiation of benign and malignant breast lesions.

RATIONALE AND OBJECTIVES: To compare the diagnostic performance of the blood pool agent feruglose and the standard extracellular contrast agent gadopentetate in their abilities to differentiate benign and malignant breast tumors. PATIENTS AND METHODS: Fourteen women, aged 35-77 years (mean, 55 years), with 19 breast lesions underwent dynamic fast field echo 14/1/30 degrees (TR/TE/alpha) magnetic resonance imaging of the breast after bolus injection of feruglose (Clariscan; Amersham Health, Amersham, UK: dose, 2 mg Fe/kg) and an additional, comparative gadopentetate (dose, 0.2 mmol gadolinium/kg)-enhanced fast field echo 10/4/30 degrees (TR/TE/alpha) magnetic resonance study within 1-11 days (mean, 4.8 days) before or after the feruglose study. All breast tumors were surgically excised within 1-6 days (mean, 2.5 days) after completion of the magnetic resonance studies. Data were analyzed by measuring quantitative enhancement data and qualitatively by categorizations of the shape of the tumor enhancement curves. Group differences between quantitative data of the two contrast agents and between benign and malignant tumors were evaluated using a two-tailed paired-sample t test. Differences in curve type distribution between benign and malignant tumors were tested with the chi2 test. RESULTS: Histopathology showed a spectrum of 10 benign and nine malignant breast lesions: five mastopathies, two fibroadenomas, two chronic inflammations, and one papillomatosis, as well as five invasive ductal carcinomas and four invasive lobular carcinomas. Substantial differences were observed between feruglose- and gadopentetate-enhanced images: the mean tumor deltaSI(%) peak enhancement and wash-in rate were significantly higher for gadopentetate- as compared with feruglose-enhanced images (P < .05). Using either contrast agent, morphologic enhancement characteristics showed a considerable overlap between benign and malignant breast lesions. However, the kinetic enhancement profiles of benign and malignant lesions were significantly different based on feruglose-enhanced data (chi2 = 9.017; P = .0027) but not gadopentetate-enhanced data (chi2 = 2.239; P = .3264). CONCLUSION: Compared with gadopentetate, the new blood pool agent feruglose provided an improved characterization of the evaluated breast lesions; however, at the cost of weaker overall tumor enhancement.

Adult↗
PubMed2003

HIV risk behaviour of older persons.

BACKGROUND: This study investigated social and psychological determinants of preventive behaviour in HIV-relevant situations. METHODS: Using computer-assisted telephone survey methodology, 2275 male and female were interviewed about their sexual habits. RESULTS: For the first time in Switzerland, data concerning HIV-relevant protection as well as their determinants were systematically collected also from persons older than 45. This age group (n=834) showed an increased risk with regard to HIV-relevant sexual contacts. CONCLUSIONS: The present findings call for more adequate monitoring of sexual behaviour of people older than 40 and suggest the development and implementation of respective age-specific prevention measures.

Adult↗
PubMed2003

Herpesvirus 8-associated penile Kaposi's sarcoma in an HIV-negative patient: first report of a solitary lesion.

Kaposi's sarcoma is a neoplastic vascular lesion. Its form of onset is frequently disseminated, especially in HIV-positive patients. Its association with the infection caused by a virus of the Epstein-Barr family, human herpesvirus 8 (HHV-8), has been recently demonstrated. In this article we discuss the unusual presentation of a solitary manifestation of Kaposi's sarcoma on the penis of a 53-year-old HIV-negative patient. Polymerase chain reaction analysis of the tumor tissue was positive for HHV-8 in the tumor cells but not in the reactive stroma cells surrounding the tumor. The case is interesting for its unusual site of presentation, the young age of onset, the association with HHV-8 infection, the HIV-negative serology, and the benign course of the disease.

DNA, Neoplasm↗
PubMed2002

Prognostic potential of the telomerase subunit human telomerase reverse transcriptase in tumor tissue and nontumorous mucosa from patients with colorectal carcinoma.

BACKGROUND: The stabilization of telomere lengths by telomerase activation is an important step in carcinogenesis and cell immortalization. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of this enzyme. The objective of this study was to evaluate the use of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for the quantification of hTERT in tumor and nontumorous tissue samples. METHODS: Matched samples of tumor and adjacent nontumorous mucosa samples from 57 patients with completely resected colorectal carcinoma (International Union Against Cancer Stage I-IV) who underwent complete resection (R0) were quantified for hTERT mRNA expression using real-time RT-PCR. The expression levels were correlated with histopathologic findings and with survival. The median follow-up was 76 months. RESULTS: hTERT mRNA was expressed in all tumor samples and in all samples of adjacent mucosa. In 12 patients (21%), there was higher hTERT expression in tumor samples compared with nontumorous samples. Compared with tumor samples, the expression of hTERT in samples of nontumorous mucosa decreased with age (P = 0.06). hTERT mRNA expression in both tumor tissue and adjacent mucosa was correlated significantly with the histologic grade of colorectal carcinoma (P < 0.04 and P < 0.05, respectively). Patients with hTERT expression in tumor tissue in relation to the adjacent mucosa of > 0.57 had a significantly poorer overall survival compared with patients with lower hTERT ratios (P < 0.02). In addition to the established prognostic factor lymphatic vessel invasion, the hTERT ratio proved to be of independent prognostic value (P < 0.05). CONCLUSIONS: The prognostic potential of hTERT in patients with colorectal carcinoma and the correlation of hTERT with tumor grade underlines the role of hTERT as a molecular marker for biologic tumor staging.

Adenocarcinoma↗
PubMed2002

Impact of grade of dysplasia in villous adenomas of Vater's papilla.

Therapeutic strategies for villous adenoma of the papilla of Vater remain controversial. This study evaluates the accuracy of preoperative histopathologic diagnosis and the impact of the grade of dysplasia on recurrence as well as on potential alteration of the surgical approach. A series of 32 patients with an adenoma of Vater's papilla who underwent local resection or pylorus-preserving pancreaticoduodenectomy between January 1990 and August 2000 were reviewed retrospectively. Multiple endoscopic biopsies had been performed preoperatively. The histopathology of the preoperatively obtained biopsy specimens and subsequent surgical specimens were evaluated for grade of dysplasia by two pathologists and correlated with the clinical course after operative treatment. Altogether, 3 of 11 patients (27%) with a low-grade (LG) dysplasia adenoma and 6 of 21 patients (29%) with a high-grade (HG) dysplasia adenoma in the initial endoscopic biopsy specimens exhibited invasive carcinoma at the postoperative histologic examination (NS). Recurrence was not observed in the 6 patients from the LG dysplasia adenoma group following local resection and benign postoperative histology. In contrast, recurrence of villous adenoma was discovered in 2 of 12 patients (17%) and development of invasive carcinoma in 5 of 12 patients (42%) from the preoperative HG dysplasia group (p <0.05). The overall risk of carcinoma after primary diagnosis of an HG dysplasia adenoma was 44% (14/32). Adenoma of the papilla of Vater including HG dysplasia appears to be associated with a high risk of exhibiting invasive carcinoma postoperatively and a high rate of recurrence. Therefore pylorus-preserving pancreaticoduodenectomy should be offered to patients with an HG dysplasia adenoma.

Adenoma, Villous↗
PubMed2002

Prognostic significance of cytokeratin-20 reverse transcriptase polymerase chain reaction in lymph nodes of node-negative colorectal cancer patients.

PURPOSE: Approximately 20% to 30% of patients with curatively resected, node-negative (pN0) colorectal cancer die of tumor recurrence, which can be caused by minimal residual disease. To identify patients with an increased risk of tumor recurrence and evaluate the prognostic value of cytokeratin-20 (CK-20), we detected CK-20-positive cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer. PATIENTS AND METHODS: Two peritumoral lymph nodes each from 85 patients with completely resected (R0) colorectal cancer without lymph node metastases (pN0) by routine examination were analyzed using a CK-20-specific reverse transcriptase polymerase chain reaction (RT-PCR) and compared with CK-20-specific immunohistochemistry (IHC). The results were correlated with histopathologic findings and with survival. RESULTS: CK-20 RT-PCR was positive in 44 patients (52%) and detected 83% of cancer-related death. Positive RT-PCR was significantly correlated with poorer overall survival (P <.009). Comparing RT-PCR with IHC, 13 patients with positive RT-PCR were identified, where the CK-20 expression was caused by tumor cell contamination located exclusively outside the lymph node capsule and had no prognostic impact. Defining these 13 patients as RT-PCR negative improved specificity of the RT-PCR assay from 57% to 75%. The 5-year overall survival of the 31 RT-PCR-positive patients was 71%, compared with 96% in the 54 negative patients (P <.001). Multivariate analysis showed expression of CK-20 mRNA to be an independent prognostic factor with a relative risk of cancer-related death of 6.1. CONCLUSION: CK-20 RT-PCR in peritumoral histopathologic tumor-free (pN0) lymph nodes of colorectal cancer is an independent prognostic factor for overall survival. Additional CK-20 IHC improves the specificity and prognostic value of RT-PCR for cancer-related death.

Aged↗