Elisabeth Oevermann

Ordinary colorectal adenocarcinomavs. primary colorectal signet-ring cell carcinoma

PURPOSE This study contributes to the characterization of primary colorectal signet-ring cell cancer in contrast to ordinary colorectal carcinoma. Primary colorectal signet-ring cell cancer is a rare but distinctive primary neoplasm of the large bowel with still-controversial clinicopathologic features. METHODS Clinicopathologic features and survival data are evaluated in comparison with those of the ordinary colorectal adenocarcinoma (non-signet colorectal carcinoma) in a retrospective study matched for age, gender, grade, and stage. RESULTS In a series of 1,600 consecutive colorectal cancer patients since 1979, 14 patients (0.88 percent) with a signet-ring cell cancer were identified. Gender ratio was balanced, and mean age was 67.5 years. The majority of patients had an advanced tumor stage at the time of diagnosis (57.1 percent Stage IV and 35.7 percent Stage III). Median survival time was only 16 months. In a study matched for age, gender, grade, and stage, a lower survival rate was found for patients with signet-ring cell cancer, but the difference did not reach statistical significance. In contrast to non-signet colorectal carcinoma, signet-ring cell cancer was characterized by a significantly higher incidence of peritoneal tumor spread (64.3 percent) and a lower incidence of hepatic metastases (14.3 percent). CONCLUSIONS Signet-ring cell cancer represents a rare but distinctive primary neoplasm of the large bowel. It is frequently diagnosed in an advanced tumor stage, thus showing an overall poorer prognosis than nonsignet colorectal carcinoma. Usually only palliative surgery is possible. A high incidence of peritoneal seeding and a low incidence of hepatic metastasis is characteristic of signet-ring cell cancer.PURPOSE: This study contributes to the characterization of primary colorectal signet-ring cell cancer in contrast to ordinary colorectal carcinoma. Primary colorectal signetring cell cancer is a rare but distinctive primary neoplasm of the large bowel with still-controversial clinicopathologic features. METHODS: Clinicopathologic features and survival data are evaluated in comparison with those of the ordinary colorectal adenocarcinoma (nonsignet colorectal carcinoma) in a retrospective study matched for age, gender, grade, and stage. RESULTS: In a series of 1,600 consecutive colorectal cancer patients since 1979, 14 patients (0.88 percent) with a signet-ring cell cancer were identified. Gender ratio was balanced, and mean age was 67.5 years. The majority of patiens had an advanced tumor stage at the time of diagnosis (57.1 percent Stage IV and 35.7 percent Stage III). Median survival time was only 16 months. In a study matched for age, gender, grade, and stage, a lower survival rate was found for patients with signet-ring cell cancer, but the difference did not reach statistical significance. In contrast to nonsignet colorectal carcinoma, signet-ring cell cancer was characterized by a significantly higher incidence of peritoneal tumor spread (64.3 percent) and a lower incidence of hepatic metastases (14.3 percent). CONCLUSIONS: Signet-ring cell cancer represents a rare but distinctive primary neoplasm of the large bowel. It is frequently diagnosed in an advanced tumor stage, thus showing an overall poorer prognosis than nonsignet colorectal carcinoma. Usually only palliative surgery is possible. A high incidence of peritoneal seeding and a low incidence of hepatic metastasis is characteristic of signetring cell cancer.

Blood Selenium and Glutathione Peroxidase Status in Patients with Colorectal Cancer

PURPOSE: It is still controversial whether a low selenium level and a reduced activity of the selenium-dependent enzyme, glutathione peroxidase, in blood are associated with an increased risk and poor prognosis of cancer in humans. This study evaluates whether colorectal cancer patients have lower serum selenium and glutathione peroxidase levels than a gender-matched and age-matched control group and whether there is a correlation to clinical data and prognosis. METHODS: In a retrospective study, serum selenium and glutathione peroxidase activity of 106 patients with colorectal cancer were determined. Clinical data were provided by our long-term follow-up program for colorectal cancer patients. RESULTS: Patients with a selenium level <70 µg/l had a significantly lower mean survival time and a lower cumulative cancer-related survival rate than patients with a selenium level >70 µg/l (P=0.0009). When considering the different tumor stages, a decline of the mean selenium level in the T4 carcinoma group was found in the analysis of variance (P<0.05). The lowest selenium level was found for patients with advanced tumor disease and in a preoperative situation,i.e., high tumor burden. In comparison with the control group, the cancer group showed a significant reduction of serum glutathione peroxidase activity (P<0.01) but no significant difference in selenium level. CONCLUSIONS: These results support the hypothesis of an association between low selenium level and advanced tumor disease. From our data, it cannot be decided whether this phenomenon is more likely to be a consequence or a causative factor for development and course of the disease.

Metachronous metastasis- and survival-analysis show prognostic importance of lymphadenectomy for colon carcinomas

BackgroundLymphadenectomy is performed to assess patient prognosis and to prevent metastasizing. Recently, it was questioned whether lymph node metastases were capable of metastasizing and therefore, if lymphadenectomy was still adequate. We evaluated whether the nodal status impacts on the occurrence of distant metastases by analyzing a highly selected cohort of colon cancer patients.Methods1,395 patients underwent surgery exclusively for colon cancer at the University of Lübeck between 01/1993 and 12/2008. The following exclusion criteria were applied: synchronous metastasis, R1-resection, prior/synchronous second carcinoma, age < 50 years, positive family history, inflammatory bowel disease, FAP, HNPCC, and follow-up < 5 years. The remaining 421 patients were divided into groups with (TM+, n = 75) or without (TM-, n = 346) the occurrence of metastasis throughout a 5-year follow-up.ResultsFive-year survival rates for TM + and TM- were 21% and 73%, respectively (p < 0.0001). Survival rates differed significantly for N0 vs. N2, grading 2 vs. 3, UICC-I vs. -II and UICC-I vs. -III (p < 0.05). Regression analysis revealed higher age upon diagnosis, increasing N- and increasing T-category to significantly impact on recurrence free survival while increasing N-and T-category were significant parameters for the risk to develop metastases within 5-years after surgery (HR 1.97 and 1.78; p < 0.0001).ConclusionsBesides a higher T-category, a positive N-stage independently implies a higher probability to develop distant metastases and correlates with poor survival. Our data thus show a prognostic relevance of lymphadenectomy which should therefore be retained until conclusive studies suggest the unimportance of lmyphadenectomy.

Influence of thymidylate synthase and p53 protein expression on clinical outcome in patients with colorectal cancer

AimsThymidylate synthase (TS) and tumor suppressor p53 are two proteins with an influence on tumor resistance to radio-chemotherapy that is well known. For this reason we tested the effect of TS and p53 expression on clinical outcome (tumor recurrence and survival) in patients after curative tumor resection, especially in patients who received adjuvant radio-chemotherapy.Patients and methodsA total of 120 patients with colorectal cancer were included in the study. A curative resection was possible in 83 patients, and 30 of this group received adjuvant therapy. For the immunohistochemical staining of tumor specimens, monoclonal antibody (mAb) TS 106 against TS and mAb DO-1 against p53 protein were used. TS positivity was defined as a moderate to high staining intensity in the cytoplasma of cells and p53 positivity as nuclear staining of tumor cells in >10% of these cells.ResultsThymidylate synthase immunoreactivity was found in 59% of all cases and p53 staining in 51%. No relation between clinicopathological features and p53 expression was found in contrast to TS expression, where a highly significant association of TS-positive cases with tumor invasion (pT) was observed. Curatively resected patients with a TS-positive tumor developed tumor recurrence/distant metastases significantly more often than TS negative tumors. The same result was found when comparing p53-positive with p53-negative tumors and TS+/p53+ with TS−/p53− tumors. TS expression was highly significantly associated with poor survival and was the strongest independent prognostic factor in multivariate analysis, followed by lymph node status.ConclusionThymidylate synthase expression seems to be an independent prognostic factor and a possible predictor of tumor recurrence in patients with colorectal cancer.

Nachsorge beim kolorektalen Karzinom

ZusammenfassungSeit 1981 wird in Lübeck Nachsorge beim kolorektalen Karzinom prospektiv durchgeführt, seit 1987 mit stadienadaptierten Programmen. Von 98% der zwischen 1979 und 1990 (präadjuvanter Zeitraum) kurativ resezierten Patienten liegen Verlaufsbeobachtungen bis Dezember 1996 vor. 36% aller Patienten entwickelten ein erneutes Tumorwachstum mit Lokalrezidiven. Fernmetastasen, Zweitkarzinomen oder multiplen Tumormanifestationen. In der univariaten Auswertung ergaben sich hochsignifikante Überlebenszeitverlängerungen für 1. regelmäßig nachgesorgte Patienten, 2. asymptomatische Patienten, 3. Patienten mit normalem CEA-Wert zum Zeitpunkt des Tumorrückfalls, 4. kurativ reoperierte Patienten, 5. palliative chirurgische Therapie gegenüber anderen palliativen Behandlungsformen. Ohne Einfluß auf die Prognose war, wer die Untersuchungen durchführte (Hausarzt/Klinik). Die Kosten für die Nachsorge betrugen zwischen 1979 und 1995 1,3 Millionen DM ohne Verwaltungs- und Koordinationskosten, was pro „geheilten” Patienten (Tumorfreiheit fünf Jahre nach Reoperation) etwa 30 000 DM beträgt.AbstractIn a prospective study regular follow-up for colorectal cancer has been performed in Lübeck since 1981. Since 1987 different programmes allowed to differentiate between high- and low-risk patients. Until December 1996 we investigated 98% of the patients who have been curatively resected between 1979 and 1990 (period before adjuvant therapy). Recurrences (local, distant, metachronous tumors or multilocular) were found in 36%. There was a significantly higher survival rate in patients with 1. intensive follow-up, 2. asymptomatic patients, 3. patients with a normal CEA level at recurrence, 4. patients with curative reoperation, 5. among the different palliative therapies surgical intervention. Patients followed-up in the hospital had no significantly higher survival rates compared to follow-up by general practitioners. Follow-up costs between 1979 and 1995 were 1.3 millions DM, for each “cured” patient (5-year recurrence-free survival after reoperation) about 30 000 DM.

Kolorektale Karzinome bei unter 40-jährigen Patienten

ZusammenfassungHintergrund:Ziel dieser Studie war, die Ergebnisse und Prognose bei Patienten jünger als 40 Jahre nach kurativer Resektion wegen eines kolorektalen Karzinoms zu evaluieren.Methodik:Innerhalb eines 24-Jahres-Zeitraums (1979–2002) wurden 1682 kurative Resektionen wegen eines primären kolorektalen Karzinoms durchgeführt. Klinische, histopathologische und Nachsorgedaten wurden prospektiv in einer Datenbank gespeichert und retrospektiv altersabhängig (≤ 40 Jahre vs. > 40 Jahre) analysiert. Im Hinblick auf die Prognose wurden folgende Endpunkte für beide Alterskollektive analysiert: Lokalrezidivrate, Inzidenz metachroner Fernmetastasen, 5- und 10-Jahres-Überlebensraten nach Kaplan-Meier (disease-free und overall survival). Statistische Berechnungen erfolgten mit Student’s t-, Mann-Whitney U-, χ2- und log-rank-Test (p < 0,05 statistisch signifikant).Ergebnisse:Von 1682 kurativ resezierten Patienten waren 1,6% (n = 26, 30-Tage-Letalität n = 0) zum Zeitpunkt der Operation 40 Jahre oder jünger. Im Vergleich zum Kollektiv der älteren Patienten (n = 1656, 30-Tage-Letalität n = 54) bestanden keine signifikanten Unterschiede hinsichtlich des Geschlechts, der Tumorlokalisation (Kolon vs. Rektum) und dem Grading (p > 0,05). 19,2% der jüngeren Patienten (5/26) hatten eine positive Familienanamnese. In der jüngeren Patientengruppe überwogen fortgeschrittene Tumorstadien (pT3 + 4: 92,3% [24/26] vs. 63,7% [1061/1656]), Karzinome mit Lymphknotenmetastasen (pN+: 53,9% [14/26] vs. 30,0% [496/1656]) sowie muzinöse bzw. siegelringzellhaltige Karzinome (11,5% [3/26] vs. 3,2% [53/1656], jeweils p < 0,05). Die Rezidivraten waren bei Patienten 40 Jahre und jünger im Vergleich zum älteren Kollektiv erhöht (Lokalrezidivrate: 15,4% [4/26] vs. 4,4% [71/1602]; Inzidenz metachroner Fernmetastasen: 23,1% [6/26] vs. 11,7% [188/1602], jeweils p = 0,02), wobei sich das mittlere rezidivfreie Zeitintervall bis zum Auftreten eines Rezidivs nicht signifikant zwischen den Altersgruppen unterschied (34,4 Monate vs. 21,3 Monate, p = 0,08). Die rezidivfreien Überlebensraten (ÜLR) zeigten keine altersassoziierten Unterschiede (5-Jahres-ÜLR: 63% vs. 61%; 10-Jahres-ÜLR: 50% vs. 45%, p > 0,05), während das overall survival bei Patienten, die 40 Jahre und jünger waren, signifikant besser war (5-Jahres-ÜLR: 79% vs. 67%; 10-Jahres-ÜLR: 72% vs. 48%, p = 0,009).Schlussfolgerungen:Die Inzidenz sporadischer kolorektaler Karzinome bei Patienten, die 40 Jahre und jünger waren, ist selten (1,6%). Den eigenen Ergebnissen zufolge überwiegen fortgeschrittene Tumorstadien, Karzinome mit Lymphknotenmetastasen und muzinöse bzw. siegelringzellhaltige Karzinome. Im Vergleich zu den älteren Patienten sind trotz erhöhter Rezidivraten keine nachteiligen Unterschiede in den rezidivfreien 5- und 10-Jahres-Überlebensraten zu beobachten.AbstractBackground:It was the aim of this study to assess the outcome of patients younger 40 years of age after curative resection for colorectal cancer (CRC) focussing on recurrence and survival.Methods:All patients with sporadic colorectal adenocarcinoma were identified by retrospective review of the prospective database registry of CRC, and grouped according to age (≤ 40 vs. > 40 years). Epidemiological, clinical, histopathological and followup data were prospectively recorded in a computerized registry. Data analyzed and compared by age-grouping were gender, tumor stage and differentiation, incidence of mucinous/signet ring cell tumors, presence of Crohn’s disease, family history, tumor site, type of curative surgery, adjuvant therapy, and follow-up data. To assess the impact on prognosis (end-points: metachronous recurrence [local and/or distant], 5- and 10-year survival rates calculated by Kaplan-Meier estimation [disease-free, overall]), statistics included Student’s t, Mann-Whitney U, χ2- and log rank test where appropriate (p < 0.05 statistically significant).Results:Within a 24-year period (1979–2002), out of 2298 patients surgically treated for CRC at our institution, 1682 patients had curative surgery: Out of these 1682, 26 patients 40 years of age or younger (incidence: 1.6%) were compared to 1656 patients older than 40 years of age.There were no statistical differences in terms of gender, tumor site and tumor differentiation between the groups (p > 0.05). 5 of 26 younger patients (19.2%) had a positive family history of colorectal cancer. In the younger patients, advanced tumor stages (pT3/4: 92.3% [24/26] vs. 63.7% [1061/1656]), lymph-node metastases (pN+: 53.9% [14/26] vs. 30.0% [496/1656]) as well as the proportion of mucinous and signet cell carcinomas (11.5% [3/26] vs. 3.2% [53/1656]) were increased when compared to the patients older than 40 years of age (p < 0.05).Within follow-up (30-day-mortality excluded), both local (LR) and distant (DR) recurrence rates were increased in the younger patients (LR: 15.4% [4/26] vs. 4.4% [71/1602] and DR: 23.1% [6/26] vs. 11.7% [188/1602], p = 0.02).The time interval to the occurrence of metachronous recurrence was not significantly different between the groups (mean 34.4 months vs. 21.3 months, p = 0.08). In terms of disease-free survival (DFS), no significant differences were noted with respect to age (5-year-DFS: 63% vs. 61%; 10-year-DFS: 50% vs. 45%, p > 0.05). However, patients 40 years of age or younger had a significantly improved overall survival (OS) (5- year-OS: 79% vs. 67%; 10-year-OS: 72% vs. 48%, p = 0.009).Conclusions:Colorectal cancer in patients 40 years of age or younger is a rare event. The younger patients present at advanced tumor stages including an increased incidence of lymph-node metastases at time of curative surgery. Nevertheless, the younger patients have equal (DFS) or even improved (OS) long-term survival prognosis when compared to patients older than 40 years of age.

Aktuelles aus der Nachsorge beim kolorektalen Karzinom

ZusammenfassungHintergrund:Ziel dieser Studie war, den Stellenwert einer konsequenten Tumornachsorge beim kolorektalen Karzinom über einen Zeitraum von 23 Jahren zu evalieren.Patienten und Methodik:Zwischen 1990 und 2002 wurden an der Chirurgischen Universitätsklinik in Lübeck 1 116 Patienten mit kolorektalem Karzinom kurativ operiert. Es wurden die Daten von 1 046 potentiellen Nachsorgepatienten ausgewertet und mit dem Kollektiv zwischen 1979 und 1989 verglichen.Ergebnisse:Die Gesamtprogressionsrate hat auf 26% abgenommen (1979–1989: 36%), hauptsächlich durch niedrigere Lokalrezidivraten nach Einführung der totalen mesorektalen Exzision (TME). Fortschritte gab es auch in der Metastasenchirurgie; die 5-Jahres-Überlebensraten nach kurativer Resektion liegen zwischen 54% (Lebermetastasen) und 89% (Lungenmetastasen). Adjuvante Therapie wurde nur von der Hälfte der Patienten akzeptiert; ein Trend zur Überlebenszeitverlängerung zeichnet sich bisher für die Kolonkarzinom-Patienten ab (mediane Überlebenszeit 52 Monate vollständige adjuvante Therapie vs. 23 Monate keine adjuvante Therapie).Schlussfolgerung:Intensive Nachsorge verbessert die Prognose. Der Anteil der bei Progression asymptomatischen Patienten ist mit 55% höher als bei Patienten mit minimalem Programm (37%).AbstractBackground:It was the aim of this study to evaluate the definite role of a standardized surveillance program for colorectal cancer within a 23-year period.Patients and Methods:1,116 patients underwent curative surgery for colorectal cancer. Out of these, 1,046 patients available for prospective follow-up were compared to a historical collective (1979–1989).Results:Tumor progression was significantly decreased from 36% to 26% which was primarily caused by the introduction of total mesorectal excision (TME). 5-year survival data for curative resections for both hepatic and pulmonary metastases (54% and 89%, respectively) were increased.Conclusion:In terms of follow-up, it could be demonstrated that complete follow-up participation positively influenced prognosis particularly related to asymptomatic patients.

Isolierte metachrone Fernmetastasen ungewöhnlicher Lokalisation nach kurativer Resektion beim kolorektalen Karzinom

ZusammenfassungEinleitung:Ziel dieser Studie war es, die Inzidenz und klinische Relevanz von isolierten metachronen Fernmetastasen (IMM) ungewöhnlicher Lokalisation nach kurativer Resektion eines kolorektalen Karzinoms zu evaluieren.Material und Methoden:IMM ungewöhnlicher Lokalisation wurden als Metastasen definiert, die ohne Nachweis eines Lokalrezidivs, ohne Nachweis von Leber- und Lungenmetastasen (weder synchron noch metachron) und ohne Nachweis eines Zweitkarzinoms jeder Lokalisation (weder synchron noch metachron) nach kurativer Resektion eines primären kolorektalen Karzinoms im Rahmen des Follow-up auftraten. Für diese Beobachtungsstudie wurde die prospektive Datenbank „Kolorektales Karzinom“ retrospektiv nach Patienten mit isolierten metachronen Fernmetastasen ungewöhnlicher Lokalisation analysiert. Nur kurativ resezierte Patienten wurden eingeschlossen. Aus einem 24-Jahres-Zeitraum (1979–2002) wurden 1682 kurative Resektionen wegen eines primären kolorektalen Karzinoms ermittelt, wobei nach Abzug der 30-Tages-Letalität (n = 54) klinische, histopathologische und Nachsorgedaten von 1628 Patienten ausgewertet wurden. Überlebenskurven wurden nach Kaplan-Meier berechnet. Statistische Berechnungen erfolgten mit Student’s t-, Mann-Whitney U-, Chi-Quadrat- und log-rank-Test (p < 0,05 statistisch signifikant).Ergebnisse:Die Inzidenz von IMM ungewöhnlicher Lokalisation lag bei 1,4% (n = 23). Lokalisationen waren Knochen (n = 6), retroperitoneale Lymphknoten (n = 5), zervikale Lymphknoten (n = 4), Pleura (n = 2), Peritoneum (n = 2), inguinale Lymphknoten, Omentum majus, Ovar und Gehirn (jeweils n = 1). Die mediane rezidivfreie Überlebenszeit bis zum Auftreten der Metastasen lag bei 13 (range 3–80) Monaten, wobei drei Viertel der Patienten klinische Symptome hatten. Die Inzidenz war signifikant mit dem Tumorstadium (91,3% [21/23] in den UICC-Stadien II und III, p < 0,05), jedoch nicht mit der Tumorlokalisation (Kolon vs. Rektum) assoziiert (p > 0,05). Bei 9 von 23 Patienten (39%) wurde erneut operiert, wobei eine kurative Resektion nur bei 13% (3/23; Omentum, Gehirn, Ovar) ohne Prognoseverbesserung durchgeführt werden konnte. Andere Therapieverfahren waren Chemo- (n = 5), Strahlen- (n = 4) und Immuntherapie (n = 1). Die Überlebensprognose der 23 Patienten war schlecht—sowohl bezogen auf die kurative Primäroperation (Überlebensraten: 44% [3 Jahre], 17% [5 Jahre], 0% [10 Jahre] bzw. mediane Überlebenszeit 33 Monate) als auch auf das Auftreten der ungewöhnlichen Metastasen (Überlebensraten: 17% [3 Jahre], 9% [5 Jahre], 0% [10 Jahre] bzw. mediane Überlebenszeit 21 Monate).Schlussfolgerungen:Die Inzidenz von IMM ungewöhnlicher Lokalisation nach kurativ reseziertem kolorektalen Karzinom ist selten. Nur wenige dieser Patienten können erneut kurativ behandelt werden. Die Überlebensprognose ist schlecht.SummaryBackgound:It was the aim of this study to assess the clinical relevance of isolated metachronous metastases (IMM) at unusual site from colorectal cancer (CRC).Material and Methods:IMM at unusual site were defined as uncommon recurrences without evidence of local recurrent disease, without occurrence of hepatic or pulmonary recurrent disease (neither synchronous nor metachronous) and without synchronous or metachronous cancer of other origin than colon or rectum following primary curative treatment for sporadic colorectal adenocarcinoma. All patients with IMM from sporadic colorectal adenocarcinoma who had been treated curatively by standardized oncologic resection, adjuvant therapy according to tumor stage and with standardized follow-up were identified by retrospective review of the computerized database registry of CRC. Within a 24-year period (1979–2002), out of 2298 patients surgically treated for CRC at our institution, 1682 patients had curative surgery (30-day mortality: n = 54), leaving 1628 patients for this analysis. Data supplied and analyzed were age, gender, tumor stage, grading, tumor site, type of curative surgery, adjuvant therapy, site of IMM, time interval, treatment of IMM, and follow-up. To assess the impact of IMM on prognosis, 3-, 5- and 10-year survival rates were calculated by Kaplan-Meier estimation. Statistics included Student’s t, Mann-Whitney U, chi-squared and log-rank test where appropriate (p < 0.05 statistically significant).Results:Out of 1628 patients treated curatively for CRC, 23 patients had IMM (incidence: 1.4%). Sites of IMM were bones (6), retroperitoneal lymph nodes (5), inguinal lymph nodes (1), cervical lymph nodes (4), pleura (2), peritoneum (2), omentum (1), ovar (1) and brain (1). Mean time interval of occurrence of IMM was 13 (range 3–80) months. The majority of patients with IMM had clinical symptoms. Occurrence of IMM was significantly associated with advanced tumor stages (p < 0.05), but not with tumor site (colon vs. rectum, p > 0.05). In terms of treatment of IMM, 9 of 23 (39%) had surgery; however, curative resection of IMM was performed in only 3 of 23 (13%) patients (omentum, brain, ovar), and did not improve survival prognosis. Other therapeutic options included chemotherapy (5), immunotherapy (1), and radiotherapy (4). Survival prognosis in patients with IMM was poor for both survival after primary CRC (3-year 44%, 5-year 17%, 10-year 0%, median survival time 33 months) and after occurrence of IMM (3-year 17%, 5-year 9%, 10-year 0%, median survival time 21 months).Conclusions:IMM after curative resection of CRC is a rare event. Derived from our results, the clinical relevance is that only the minority can be treated curatively and that patients with IMM have a poor survival prognosis.

Serumtest für C3a Anaphylatoxin ermöglicht minimal-invasives Screening für kolorektale Tumoren

Background: Late diagnosis of colorectal carcinomas results in a significant reduction of average survival times. However, despite screening programs, about 70 % of tumors are detected at advanced stages (UICC III/IV). We therefore aimed at detecting tumor-specific protein biomarkers in serum samples that could potentially be applied for early diagnostics. Methods: A discovery set of sera from patients with colorectal malignancy (n = 58) and healthy control individuals (n = 32) were evaluated for potential differences using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF). Candidate markers were identified and validated using enzyme-linked immunosorbent assays (ELISA). Results: Several m/z values were expressed differentially between malignant and healthy control samples of the discovery set. Identification of the most prominent m/z value revealed C3a anaphylatoxin (C3a-desArg). ELISA based C3a-levels allowed correct classification of serum samples within the blinded validation set with 96 % sensitivity and specificity. Increased serum levels detected also 86 % of an independent sera (n = 36) set from patients with colorectal adenomas. Conclusions: Increased serum levels of C3a-desArg allowed correct group classification of patients with colorectal adenomas and carcinomas with high sensitivity and specificity (both 96 %, p < 0.0001). C3a-desArg serum level assessment could thus ameliorate existing screening tests for colorectal cancer.