[show abstract][hide abstract] ABSTRACT: To evaluate local control for long-term prognosis in retroperitoneal soft-tissue sarcoma (primary tumors (PT) and local recurrence (LR)).
A total of 110 patients underwent surgery between 1988 and 2002. Prospectively gathered clinicopathological data were analyzed. Kaplan-Meier estimations and Cox regression analyses were performed.
Resectability was 90%, being comparable for PT (n=71) and LR (n=39). Morbidity, mortality, blood loss, and operation time did not differ for PT or LR (24% vs. 31%, p=0.41; 7.0% vs. 5.1%, p=1.0; 1000 ml vs. 1500 ml, p=0.17; 240 min vs. 255 min, p=0.13). Hospitalization was comparable in both groups (median, 12 days (PT) and 13 days (LR)). Follow-up was 89 months (median, IQR 37-112 months). Local 3- and 5-year control rates after complete resection of PT were 66% and 59% (19% and 9% for LR, p<0.001). The mean number of operations were 1.4 for PT and 2.4 for LR (p=0.0047). The 5-year survival rates after complete resection were 51% for PT and 43% for LR (p=0.39). The 5-year survival rates were 65%, 4%, and 0% for complete resection, incomplete resection, and exploration, respectively (p<0.001). Multivariate analysis showed high-grade and blood loss with a poor prognosis.
Comparable resectability rates and perioperative outcome were observed for surgery of PT and LR. Consequent reoperation leads to respectable long-term survival rates after resection of LR. The prognosis in retroperitoneal sarcomas varies significantly according to resectability, grade and blood loss.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 01/2009; 35(9):986-93. · 2.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Positron emission tomography (PET) using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) is used as a functional imaging technique for the staging and follow-up of lymphomas. However, additional information about the tumor proliferation rate using 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) may be useful for the assessment of prognosis. We enrolled 48 patients with Hodgkin's (n = 15) and non-Hodgkin's lymphoma (n = 33) with residual masses >2 cm examined by tracer studies with FDG and FLT. The results were related to median overall and progression-free survival. In 15 out of 48 patients analysed using FDG, positive results were found. Using FLT, 10 out of 48 patients were positive. 33 patients were FDG negative. Eight patients were positive both using FDG and FLT. Overall survival for patients with a negative PET scan was significantly higher than for patients with positive PET, irrespective of the tracer used. FLT alone was able to discriminate between patients with long or short overall survival. However, there was no statistical significance comparing FDG/FLT negative versus FDG negative alone. Although FDG detected more lesions than did FLT, the additional biological characterization of tumor tissue with respect to proliferation by FLT might be useful by providing complementary information for the identification of recurrence. However, the present data show no advantage of combined FDG/FLT studies over FDG alone with respect to the prediction of survival.
Leukemia and Lymphoma 04/2007; 48(4):746-53. · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to determine whether anti-p53 antibodies are of clinical significance as a serological marker in the diagnosis and monitoring of malignancies. A total of 1874 serum samples from 591 patients with various types of cancer, esophageal, gastric, colorectal, pancreatic, hepatocellular, breast, and urogenital cancer, and 436 control individuals were analyzed by immunoblot for antibodies against p53. The anti-p53 antibody test was correlated with expression of conventional tumor markers, survival and the clinicopathological features of malignant disease. Anti-p53 antibodies were found in 23.4% (138/591) of the sera of patients with malignant disease (range 11.5-34%). The detection of anti-p53 serum antibodies had a specificity of 100% for malignancy (p<0.0001). The overall sensitivity of measuring established tumor markers was 62.9% (372/591). The elevation of conventional tumor markers and the presence of anti-p53 antibodies in the sera of patients with malignant disease turned out to be an independent variable (p<0.05). Combination of established tumor markers with the anti-p53 antibody test led to an increase in diagnostic sensitivity of 8% (49/591) (p<0.01). Thus, the independence of anti-p53 antibodies from established tumor markers allows the serological detection of additional tumor patients. Kaplan-Meier analysis revealed a trend toward a poorer prognosis in hepatocellular carcinoma and breast cancer patients who were anti-p53 serum positive. In conclusion, testing for anti-p53 antibodies can increase the diagnostic sensitivity when used in combination with measurement of conventional tumor markers. This increase is achieved without a parallel decrease in specificity.
International Journal of Oncology 10/2006; 29(4):973-80. · 2.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Surgery has been the only effective therapy. However, many patients still eventually die of disease recurrence. Chemotherapy and radiation therapy have been of limited value. Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany.
We summarized the data of 16 patients with advanced or metastatic GIST treated with imatinib mesylate in palliative and neoadjuvant settings.
Overall response was 81%, with no evidence of disease (NED) in 3/16 (19%), partial response (PR) in 9/16 (56%) and stable disease (SD) in 1/16 (6%), whereas 3/16 patients (19%) suffered from progressive disease (PD). Mean follow-up was 18.6 months [range: 4-30]. Mean progression-free survival (PFS) was 17.6 months [range: 0-30], mean overall survival (OS) from initial diagnosis was 32.3 months [range: 5-122]. Most common side effects were periorbital edema and skin rash.
Imatinib mesylate is well tolerated in a dose of up to 800 mg/day and has significant activity during long- term treatment of patients with advanced or metastatic GIST.
[show abstract][hide abstract] ABSTRACT: Loss of CD95 expression in tumour cells occurs frequently in colon carcinoma and may be associated with disease progression. On the other hand, neo-expression of CD95L in tumour cells may contribute to immune evasion.
We aimed at further exploring the functional role and prognostic significance of the CD95/CD95L death inducing system in colon carcinomas.
CD95 and CD95L expression was examined by immunohistochemistry in 128 R0 resected UICC (International Union against Cancer) stage II/III colon carcinomas and correlated with disease free survival.
CD95 expression in tumour cells was observed in only 30 carcinomas (23.4%) whereas the others had at least a minor subpopulation of CD95 negative cells. Loss of CD95 in tumour cells was related to adverse prognosis in uni- and multivariate analysis (p = 0.046 and p = 0.036, respectively). Tumour infiltrating lymphocytes (TIL) were the major source of CD95L in colon carcinomas. CD95L+TIL were present in 83% of cases whereas CD95L was found in tumour cells in only 12% of cases. Moreover, a high rate of CD95L+TIL correlated with prolonged disease free survival in patients with UICC stage II (p = 0.05) but not in those with stage III.
Loss of CD95 in tumour cells may be an independent prognostic factor in colon carcinomas. The CD95L counterattack is not a relevant feature in colon carcinoma but CD95L+TIL may contribute to tumour control in the early stages of the disease, exerting a concurrent selection pressure in the direction of CD95 abrogation/resistance.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to evaluate the prognostic significance of preoperative positron emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose (FDG) by calculating the mean standardized uptake values (SUV) in patients with resectable soft tissue sarcomas (STS).
FDG-PET might be used as an adjunctive tool (in addition to biopsy and radiologic tomography) in the preoperative prognostic assessment of resectable STS.
A total of 74 adult patients with STS underwent preoperative FDG-PET imaging with calculation of the SUV. Clinicopathologic data and the SUV were analyzed for an association with the clinical outcome. The first and the third quartiles of the SUV distribution function were used as cutoff values (1.59 and 3.6). Survival was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and the Cox proportional hazards regression model.
In 55 cases, STS were completely resected (follow up 40 months): 5-year recurrence-free survival rates in patients with SUV <1.59, 1.59 to <3.6, and > or =3.6 were 66%, 24%, and 11%, respectively (P = 0.0034). SUV was a predictor for overall survival (5-year rates: 84% [SUV <1.59], 45% [SUV 1.59 to <3.6], and 38% [SUV > or =3.6]; P = 0.057) and local tumor control (5-year rates: 93% [SUV <1.59], 43% [SUV 1.59 to <3.6], and 15% [SUV > or =3.6]; P = 0.0017). By multivariate analysis, SUV was found to be predictive for recurrence-free survival. The prognostic differences with respect to the SUV were associated with tumor grade (P = 0.002).
The semiquantitative FDG uptake, as measured by the mean SUV on preoperative PET images in patients with resectable STS, is a useful prognostic parameter. SUV with cutoff values at the first and the third quartiles of the SUV distribution predicted overall survival, recurrence-free survival, and local tumor control. Therefore, FDG-PET can be used to improve the preoperative prognostic assessment in patients with resectable STS.
Annals of Surgery 02/2005; 241(2):286-94. · 6.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study aimed to determine the prevalence of psychiatric morbidity and distress among 189 consecutively recruited cancer patients upon admission to surgical oncology wards, and to investigate the recognition of distressed patients by medical staff.
Assessment consisted of a diagnostic psychiatric interview (SCID, DSM-IV), patient-reported distress using a standardised questionnaire (Hospital Anxiety and Depression Scale), and physicians' and nurses' estimates of patients' distress. Twenty-eight per cent of patients were assigned a psychiatric diagnosis, with adjustment disorder predominating.
Surgeons accurately recognised marked distress in 77% of patients with a psychiatric disorder and nurses did so in 75%. Because of low specificity, the positive predictive value was only 39% in surgeons and 40% in nurses. However, recognition of distress translated into referral to the psychosocial liaison service for only a minor proportion of distressed patients.
Since a remarkable proportion of distressed patients remained unrecognised by the medical staff, only systematic screening of patients upon admission allows timely support to those who are most in need.
Annals of Oncology 09/2004; 15(8):1243-9. · 7.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: The role of high-dose chemotherapy (HDCT) with PBSCT in the treatment of bone and soft-tissue sarcomas is not established. In total, 27 patients (15 female, median age at TPL 30.6 years (range: 13-59)) were analyzed (Ewing sarcoma family n=8, osteosarcoma n=6, MPNST (malignant peripheral nerve sheath tumor) n=4, synovial sarcoma n=3, liposarcoma n=2, leiomyosarcoma n=2, rhabdomyosarcoma n=1, meningosarcoma n=1). Following chemotherapy and surgery complete remission (CR) (n=9), partial remission (PR) (n=10), stable disease (SD) (n=2) and progressive disease (PD) (n=6) were reached prior HDCT. Different HDCT conditioning regimens were used. One patient died due to cardiac arrest after HDCT. Except hematologic side effects, no WHO grade III-IV complications were observed. Four patients died within 6 months due to PD, disease recurred in another seven patients and led to death, 15 patients are alive with/without disease. The median progression-free survival (PFS) is 12.0 months (range: 0-58), in nine CR patients median PFS is 25.8 months (range: 3-58). Although the role of HDCT in the treatment of sarcomas is not defined, a subgroup of patients who achieved CR before HDCT could benefit from this therapy.
Bone Marrow Transplantation 08/2004; 34(1):37-41. · 3.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Jejunal pouch formation and restoration of duodenal transit have been suggested for reconstruction after total gastrectomy. Opinions about the clinical value vary.
The literature was searched for prospective randomized trials comparing reconstructive procedures after total gastrectomy for malignancy. Reports with at least an English or German abstract were included. Immediate results were evaluated in terms of postoperative deaths and complications. Long-term outcome was analysed using trends in bodyweight and quality of life.
A total of 19 randomized trials including 866 patients was identified. The operative risk of total gastrectomy was low, with a median mortality rate of 0 (range 0-22) per cent, irrespective of the method of reconstruction. Neither gastric substitution nor restoration of duodenal transit was associated with significant procedure-related complications. Results for specific reconstructions varied considerably within and between individual trials. Jejunal pouch reconstruction, but not restoration of duodenal passage, was associated with improved food intake and a tendency for weight gain in the early postoperative months. A favourable perception of quality of life persisted in the long term in some studies.
Preservation of duodenal transit offers little clinical benefit. Construction of a small-bowel reservoir after total gastrectomy should be considered to improve early postoperative eating capacity, bodyweight and quality of life.
British Journal of Surgery 06/2004; 91(5):528-39. · 4.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has long been suspected that mechanical influences may enhance the release of viable colorectal cancer cells into the circulation. The objective of this study was to determine the extent of hematogenous tumor cell spread in colorectal cancer patients during colonoscopy.
Peripheral venous blood samples were taken before and after colonoscopy from 44 patients with colorectal cancer. Blood samples were examined using a reverse-transcriptase polymerase chain reaction assay to amplify cytokeratin 20 transcripts.
Eleven patients with colorectal cancer displayed circulating tumor cells before and after colonoscopy (25%), whereas tumor cells were detected in six of 44 patients (14%) only after the procedure (p = 0.03, McNemar's test: tumor cell detection before after colonoscopy). All control samples consistently tested negative.
Mechanical forces may result in enhanced release of viable colorectal cancer cells into the circulation; however, the clinical significance of these results needs to be clarified.
[show abstract][hide abstract] ABSTRACT: Die Leberresektion zur Behandlung von Metastasen solider Tumoren mit kurativer Zielsetzung kann heute mit einer akzeptablen perioperativen Morbiditt und Letalitt (<3%) durchgefhrt werden. Die meisten Erfahrungen liegen mit den Metastasen kolorektaler Karzinome vor. Die Fnfjahresberlebensraten betragen hier bei primrer, aber auch bei wiederholter, Metastasenresektion jeweils 25–30%. Allerdings sind zum Zeitpunkt der Diagnose lediglich knapp 20% der Patienten durch eine Leberresektion potenziell kurvativ behandelbar. Stand bisher die intra- und postoperative Risikominimierung als Voraussetzung fr eine gute Langzeitberlebensrate im Vordergrund, so erscheint eine Prognoseverbesserung knftig in erster Linie durch eine Erweiterung der Indikations- und Therapiespektren mglich. Zwar haben adjuvante Therapiemanahmen nach Leberresektion bisher keine Erfolge gezeitigt, doch konnte bei Ansprechen auf eine Induktionstherapie bei ca. 15% der Patienten mit primr nicht resektablen Metastasen sekundr eine vollstndige Metastasenresektion mit kurativer Zielsetzung durchgefhrt werden. Darber hinaus ist zu erwarten, dass die Kombination der Leberresektion mit interventionellen Verfahren sowie eine weitere chirurgische Spezialisierung es ermglichen, bis dato nicht resektable Lebermetastasen operativ anzugehen. Die Kombination resezierender und thermoablativer Verfahren, die selektive portale Embolisation, mehrzeitige Leberresektionen und die Mglichkeiten multimodaler Therapiekonzepte bei primr nicht kurativ operablen Befunden mssen knftig in klinischen Studien systematisch berprft werden.Liver resection for metastatic disease can be performed with curative intent at low operative mortality (<3%). To date, most experience relates to colorectal liver metastases. Five-year survival following primary and repeat liver resection has consistently been reported to be 25–30%. Although adjuvant chemotherapy following liver resection has been ineffective, induction chemotherapy results in secondary resectability of liver metastases in a substantial number of patients.Future strategies should, therefore, aim to increase the number of patients amenable to potentially curative liver resection. This could be achieved by earlier diagnosis, by combination of liver resection with induction chemotherapy or thermoablation and selective portal vein embolization as well as further surgical specialization. All these novel approaches require systematic testing preferably by randomized trials.
Der Onkologe 04/2004; 10(5):474-491. · 0.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gastrointestinal stromal tumours (GISTs), the most common mesenchymal tumours of the digestive tract, are largely resistant to chemo- and radiotherapy. They are currently defined by their overexpression of the KIT receptor tyrosine kinase (CD117), a member of the family of receptor tyrosine kinases (RTKs), and exhibit KIT mutations in more than 85% of cases. Additionally, in more than one-third of KIT wild-type GISTs, mutations of platelet-derived growth factor receptor alpha (PDGF-R alpha), which also belongs to the family of RTKs, were recently found. Since these data indicate that uncontrolled RTK signalling may be implicated in the pathogenesis of GISTs, RTKs and the activated downstream signalling cascades are attractive targets in the therapy of these tumours. Imatinib is a small-molecule inhibitor that selectively blocks the activity of the PDGF-R, ABL and KIT receptor tyrosine kinases by competitive binding to the adenosine triphosphate binding site of their catalytic domains. We herein review the molecular pathological, preclinical and clinical data that identify imatinib as a valuable new agent in the treatment of GISTs.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 03/2004; 444(2):108-18. · 2.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: The biliary epithelium of bile ducts and gallbladder modifies the composition of primary hepatic bile by absorption and secretion of an electrolyte-rich fluid. The underlying transport mechanisms, however, are still incompletely understood. We investigated the expression, the cellular localization, and the functional role of guanylin, a bioactive intestinal peptide involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-regulated electrolyte/water secretion, in the human gallbladder.
Peptide-specific antibodies were raised to localize guanylin and its affiliated signaling proteins, i.e., the guanylin receptor, guanylate cyclase C (GC-C), cGMP-dependent protein kinase type II (cGKII), and CFTR in the human gallbladder and cholangiocarcinoma cells (Mz-Cha-1) by RT-PCR, Western blot, and immunocytochemistry. A sensitive ELISA was used to assess the range of guanylin concentration in human bile fluid. The functional role of guanylin was investigated in subconfluent Mz-Cha-1 cell monolayers by isotope efflux experiments.
Guanylin and its affiliated signaling proteins are highly expressed in the human gallbladder. Guanylin is localized to secretory epithelial cells of the gallbladder and is present in the bile, whereas GC-C, cGKII, and CFTR are confined exclusively to the apical membrane of the same epithelial cells. Functional studies in Mz-Cha-1 cells identify guanylin as a specific regulator of biliary Cl(-) secretion that very likely is mediated by an intracellular increase of cGMP-concentration.
Based on the present findings and on the functional role of guanylin in other epithelia, it is likely that gallbladder epithelial cells synthesize and release guanylin into the bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.
[show abstract][hide abstract] ABSTRACT: Benign neurofibromas and malignant peripheral nerve sheath tumours (MPNST) commonly develop in patients with neurofibromatosis. Differentiation of benign from malignant tumours by conventional preoperative imaging is unreliable. FDG-PET is a non-invasive technique for biological tumour evaluation. The aim of this study was to assess the value of FDG-PET in patients with neurogenic tumours suspicious for MPNST.
Benign and malignant neurogenic soft tissue tumours were prospectively evaluated by computed tomography or magnetic resonance imaging. Three-dimensional qualitative and quantitative FDG-PET was performed. Standard uptake value (SUV) was analyzed with respect to histological diagnosis and follow-up data.
Twenty-five neurogenic soft tissue tumours were included. FDG-PET identified all primary (n=6) and recurrent MPNST (n=7). Benign lesions (n=12) did not demonstrate high FDG uptake. The SUV was significantly higher in MPNST (median 2.9; range 1.8-12.3), than in benign tumours (median 1.1; range 0.5-1.8) (p<0.001). At a cut-off value of 1.8 SUV measured 1 h post-injection FDG-PET distinguished between MPNST and benign neurogenic tumours with 100% sensitivity and 83% specificity.
FDG-PET allows discrimination of benign from malignant neurogenic tumours. This should be particularly useful in patients with neurofibromatosis as FDG-PET may help to avoid multiple surgical procedures for benign tumours.
European Journal of Surgical Oncology 09/2003; 29(6):536-41. · 2.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: Apoptosis is a key event in the pathophysiology of many liver diseases. Primary human hepatocytes (PHH) provide a useful model to study physiological and pathophysiological processes in the liver. Our aim was to optimize PHH cultures to allow studies on induction of apoptosis and of hepatitis B virus (HBV) infection.
PHH were isolated from human liver tissue by two-step collagenase perfusion. PHH and hepatoma cells were treated with different apoptosis-inducing agents in parallel. PHH cultures were infected with wild type HBV and transduced with HBV genomes using adenoviral vectors.
PHH were successfully isolated from 40 different tissue samples with high viability and purity. Perfusion time and seeding density turned out to be critical parameters for optimal cell yield and culture conditions, respectively. Serum addition to the medium reduced viability of PHH. PHH allowed reproducible studies of CD95-dependent and -independent apoptosis. Sensitivity towards CD95-mediated apoptosis was markedly higher than in hepatoma cells. PHH could efficiently be infected with HBV, but infection did neither induce apoptosis nor prevent CD95-induced cell death.
Our data show that PHH provide an excellent tool for the investigation of apoptosis induced by agents like death receptor-ligands and hepatotropic viruses.
Journal of Hepatology 07/2003; 38(6):736-44. · 9.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent morphological and molecular genetic findings have greatly expanded our understanding of gastrointestinal stromal tumors (GISTs). GISTs are now defined by their overexpression of CD117 (KIT), the receptor for the stem cell factor, and can thus be discriminated from smooth muscle tumors. Cytogenetically, GISTs are characterized even in early lesions by frequent entire or partial loss of the chromosomes 14 and 22 and terminal deletions of the chromosomal arm 1p. During tumor progression further chromosomal imbalances accumulate. Following the first report on activating KIT mutations in GISTs, several studies have addressed the role of wild-type and mutant KIT in GISTs and demonstrated activating KIT mutations in the majority of cases. Moreover, KIT tyrosine phosphorylation is even present in KIT mutation-negative GISTs, implicating KIT activation as a central event in the pathogenesis of GISTs. Imatinib (STI571/Glivec) is a selective inhibitor of BCR/ABL, PDGFR and KIT receptor-tyrosine kinases. First therapeutic applications of imatinib in patients with progressive GISTs have yielded promising results. This review focuses on the morphological and molecular findings in GISTs which have opened up a new therapeutic perspective.
Der Pathologe 06/2003; 24(3):182-91. · 0.62 Impact Factor
[show abstract][hide abstract] ABSTRACT: Zusammenfassung Neuere morphologische und molekulare Befunde haben unser Verstndnis ber gastrointestinale Stromatumoren (GIST) betrchtlich erweitert. Gastrointestinale Stromatumoren werden gegenwrtig ber ihre berexpression von CD117 (KIT), dem Rezeptor des Stammzellfaktors, definiert und so gegenber glattmuskulren Tumoren abgegrenzt. Zytogenetisch sind GIST bereits in frhen Stadien durch hufige komplette oder partielle Verluste der Chromosomen 14 und 22 und terminale Deletionen des Chromosomenarms 1p charakterisiert. Im Verlauf der Tumorprogression wird eine Akkumulation von zustzlichen chromosomalen Anomalien beobachtet. Basierend auf der Erstbeschreibung von aktivierenden KIT-Mutationen in GIST haben sich zahlreiche Studien mit der Rolle von wildtypischem und mutiertem KIT in GIST beschftigt. Inzwischen wurden in der berwiegenden Mehrheit der GIST KIT-Mutationen identifiziert und selbst in KIT-Mutation-negativen GIST eine konstitutive Phosphorylierung der KIT-Rezeptor-Tyrosinkinase nachgewiesen. Diese Befunde lassen darauf schlieen, dass KIT eine zentrale Rolle bei der Pathogenese von GIST spielt. Imatinib (STI571/Glivec) inhibiert selektiv die BCR/ABL-, die PDGFR- und die KIT-Rezeptor-Tyrosinkinasen. Erste therapeutische Anwendungen von Imatinib bei Patienten mit progredienten GIST haben in dieser chemo- und radiotherapieresistenten Tumorentitt beachtliche Ergebnisse erzielt. In dieser bersicht werden die morphologischen Befunde und molekularen Grundlagen von GIST dargestellt, die eine neue therapeutische Perspektive erffnet haben. Summary Recent morphological and molecular genetic findings have greatly expanded our understanding of gastrointestinal stromal tumors (GISTs). GISTs are now defined by their overexpression of CD117 (KIT), the receptor for the stem cell factor, and can thus be discriminated from smooth muscle tumors. Cytogenetically, GISTs are characterized even in early lesions by frequent entire or partial loss of the chromosomes 14 and 22 and terminal deletions of the chromosomal arm 1p. During tumor progression further chromosomal imbalances accumulate. Following the first report on activating KIT mutations in GISTs, several studies have addressed the role of wild-type and mutant KIT in GISTs and demonstrated activating KIT mutations in the majority of cases. Moreover, KIT tyrosine phosphorylation is even present in KIT mutation-negative GISTs, implicating KIT activation as a central event in the pathogenesis of GISTs. Imatinib (STI571/Glivec) is a selective inhibitor of BCR/ABL, PDGFR and KIT receptor-tyrosine kinases. First therapeutic applications of imatinib in patients with progressive GISTs have yielded promising results. This review focusses on the morphological and molecular findings in GISTs which have opened up a new therapeutic perspective.
Der Pathologe 04/2003; 24(3):182-191. · 0.62 Impact Factor