Heike Zettl

Incidence, therapy and prognosis of colorectal cancer in different age groups. A population-based cohort study of the Rostock Cancer Registry.

Purpose:Determination of frequency, treatment modalities used and prognoses of colorectal cancer in a population-specific analysis in relation to age.Material and Methods:In 1999 and 2000, 644/6,016 patients were documented as having colorectal carcinomas in the Cancer Registry of Rostock. 39 patients were excluded (16 cases: “in situ” carcinomas; 23 cases: insufficient data). Three age groups were formed: < 60 years, 60–74 years; ≥ 75 years.Results:The relative percentage of colorectal cancer increases with advanced age (< 60 years 7%; 60–74 years 12%, ≥ 75 years 15%; p < 0.001).In older patients with stage III carcinomas, adjuvant treatment was done less frequently in accordance with the treatment recommendations (< 60 years 83–89%; 60–74 years 67–77%; ≥ 75 years 29–36% according to stage and tumor localization); in stage IV, the use of chemotherapy was reduced (< 60 years 87.5–100%; 60–74 years 38–47%; ≥ 75 years 33–37%).In the univariate analysis, age ≥ 75 years (4-year survival rates: < 60 years 68 ± 4.1%; 60–74 years 58 ± 2.8%; ≥ 75 years 38 ± 3.7%), UICC stage and surgical treatment had a significant effect on prognosis. Adjuvant treatment had no significant effect on the whole population but on patients with UICC stage III and IV.In the multivariate analysis, however, the only independent prognostic parameters were age ≥ 75 years (p = 0.001), performance of chemotherapy (colon cancer) or radiochemotherapy (rectal cancer; p = 0.004–0.001), and tumor stage (p = 0.045–0.001). Sex (p = 0.063) and age between 60 and 74 years (p = 0.067) had a borderline influence.Conclusion:With increasing age, there is a departure in daily practice from the treatment recommendations. The patient’s prognosis is dependent upon age (especially ≥ 75 years), tumor stage, and therapy.Ziel:Bestimmung der Häufigkeit, der Therapiemodalitäten und der Prognose von Patienten mit kolorektalen Tumoren in einer bevölkerungsspezifischen Analyse in Bezug auf das Alter.Material und Methodik:Zwischen 1999 und 2000 wurden im Krebsregister Rostock 644/6 016 Patienten mit kolorektalen Karzinomen dokumentiert. 39 Patienten wurden ausgeschlossen (16 Fälle: In-situ-Karzinome; 23 Fälle: Insuffiziente Daten). Drei Altersgruppen wurden gebildet: < 60 Jahre, 60–74 Jahre, ≥ 75 Jahre.Ergebnisse:Der relative Anteil kolorektaler Karzinome steigt mit zunehmendem Alter (< 60 Jahre 7%; 60–74 Jahre 12%; ≥ 75 Jahre 15%; p = 0,001).Mit zunehmendem Alter wurden im Stadium III die Behandlungen weniger häufig in Übereinstimmung mit den Therapieempfehlungen durchgeführt (< 60 Jahre 83–89%; 60–74 Jahre 67–77%; ≥ 75 Jahre 29–36% gemäß Stadium und Tumorlokalisation); im Stadium IV nahm der Anteil der Patienten, die eine Chemotherapie erhielten, mit zunehmendem Alter ab (< 60 Jahre 87,5–100%; 60–74 Jahre 38–47%; ≥ 75 Jahre 33–37%).In der univariaten Analyse hatten das Alter ≥ 75 Jahre (4-Jahres-Überlebensraten: < 60 Jahre 68 ± 4,1%; 60–74 Jahre 58 ± 2,8%; ≥ 75 Jahre 38 ± 3,7%), das UICC-Stadium und die chirurgische Therapie einen signifikanten Effekt auf die Prognose. Eine adjuvante Behandlung zeigte für das gesamte Kollektiv mit Ausnahme von Patienten im UICC-Stadium III und IV keine signifikante Wirkung. In der multivariaten Analyse sind dagegen nur das Alter ≥ 75 Jahre (p = 0,001); die Durchführung einer Chemotherapie (Kolonkarzinom) oder Radiochemotherapie (Rektumkarzinom; p = 0,004–0,001) und das Tumorstadium (p = 0,045–0,001) unabhängige prognostische Parameter. Ein Alter zwischen 60 und 74 Jahren (p = 0,067) sowie das Geschlecht (p = 0,063) hatten nur einen grenzwertigen Einfluss.Schlussfolgerung:Mit zunehmendem Alter ist in der täglichen Praxis ein Abweichen von den Therapieempfehlungen festzustellen. Die Prognose der Patienten mit kolorektalen Karzinomen ist abhängig vom Alter (insbesondere ≥ 75 Jahre), vom Tumorstadium und von der Therapie.

Differences Between Clinical Trial Participants and Patients in a Population-Based Registry : the German Rectal Cancer Study vs. the Rostock Cancer Registry

PURPOSE: There are few data on whether the samples of randomized phase III studies are representative for cancer patients in general populations. METHODS: We compared patient and disease characteristics of patients with stage II or III rectal cancer from the German Rectal Cancer Study (657 patients, 1995-2002) or the Rostock Cancer Registry (371 patients, 1997-2003). Differences between the Study and the Registry were analyzed for subgroups who received neoadjuvant chemoradiotherapy before resection or primary resection with or without postoperative chemoradiotherapy. RESULTS: Study and Registry patients differed in age (median, 61.7 vs. 65.0 years, P < 0.001) and proportion of women (31.3 percent vs. 38.4 percent, P < 0.004). Significant age and gender differences were seen in primary resection but not in neoadjuvant subgroups. In neoadjuvant and in primary resection subgroups, Study participants were more likely than Registry patients to have tumor location in the lower third of the rectum, a higher rate of R0 resection, a greater number of lymph nodes assessed, and fewer T4 tumors. In the primary resection subgroups, Study participants were more likely to have received postoperative chemoradiotherapy. Multivariate analyses showed no effect of population type (Study vs. Registry) on disease-free or overall survival in neoadjuvant subgroups, but increased risk for Registry patients in primary resection subgroups. CONCLUSIONS: Participants in clinical trials such as the German Rectal Cancer Study are not representative of all cancer patients of a general population. To enable wider extrapolation of results, future studies should include elderly and high-risk patients.

Prognostic and diagnostic implications of epithelial cell adhesion/activating molecule (EpCAM) expression in renal tumours: a retrospective clinicopathological study of 948 cases using tissue microarrays.

To evaluate the expression and prognostic value of epithelial cell adhesion/activating molecule (EpCAM) in a large set of renal cell carcinomas (RCCs) using a tissue microarray (TMA) approach.

Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair‐deficiency and Lynch syndrome

Mismatch‐repair deficient (MMR‐D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood‐form of constitutional mismatch repair‐deficiency (CMMR‐D); caused by bi‐allelic MMR gene mutations. A hallmark of LS‐associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR‐D patients are thought to display a somatic mutation pattern differing from LS. This study has the main goal to identify cFSM in MSI target genes relevant in CMMR‐D and to compare the spectrum of common somatic mutations, including alterations in DNA polymerases POLE and D1 between LS and CMMR‐D. CMMR‐D‐associated tumors harbored more somatic mutations compared to LS cases, especially in the TP53 gene and in POLE and POLD1, where novel mutations were additionally identified. Strikingly, MSI in classical mononucleotide markers BAT40 and CAT25 was frequent in CMMR‐D cases. MSI‐target gene analysis revealed mutations in CMMR‐D‐associated tumors, some of them known to be frequently hit in LS, such as RNaseT2, HT001, and TGFβR2. Our results imply a general role for these cFSM as potential new drivers of MMR‐D tumorigenesis.

C-kit overexpression is not associated with KIT gene mutations in chromophobe renal cell carcinoma or renal oncocytoma

INTRODUCTION C-kit overexpression has previously been described in chromophobe renal cell carcinoma (cpRCC) and renal oncocytoma (RO). However, so far no KIT mutations have been found. The objective of our study was to analyse c-kit in a large cohort of renal tumors and to perform KIT mutation analysis in a subset cpRCC and RO cases with overexpression of c-kit. MATERIALS AND METHODS We studied the immunohistochemical expression of c-kit on tissue microarrays containing formalin-fixed, paraffin-embedded samples of 948 patients with renal tumors. CpRCC and RO cases with c-kit overexpression (n=23) were analyzed for KIT mutations in exons 9, 11, 13, 14, 15, and 17. RESULTS Expression of c-kit was found in 6/642 (0.9%) clear cell RCC, 3/154 (1.9%) papillary RCC, 54/69 (78.3%) cpRCC, 37/45 (82.2%) RO and 2/30 (6.7%) of other unclassified tumor types. In none of the RO and cpRCC cases analyzed, a KIT gene mutation was found. CONCLUSION C-kit expression is found in the majority of cpRCC and RO, but these tumors do not harbor the usual c-kit activating mutations. This may have implications for the use of tyrosine kinase inhibitors in patients with advanced cpRCC and c-kit expression.

Frequent and Yet Unreported GNAQ and GNA11 Mutations are Found in Uveal Melanomas

Malignant melanoma of the uvea is the most common primary malignant tumor in the eye. We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using formalin-fixed, paraffin-embedded material and correlate the results with clinicopathological parameters. Tumor tissue was microdissected followed by amplification of GNAQ exon 4 and 5, GNA11 exon 4 and 5, and finally analyzed by Sanger sequencing. A total of 64.4 GNA11/GNAQ mutations, including ten yet unreported, were found. Two cases showed multiple mutations. Overall survival was significantly shorter in the uveal melanoma cohort with GNAQ exon 5 mutation. In concordance with previous studies, high frequencies of mutations in GNAQ or GNA11 were detected. Interestingly, in about 20% of UM, not yet reported mutations in GNAQ or GNA11 were seen. Rarely, uveal melanoma may harbor double mutations in GNAQ and/or GNA11. Recent data imply, that implementation of GNAQ/GNA11 mutation analysis in routine diagnostic procedures might be helpful for future therapeutic decisions.

Expression and clinicopathological correlations of retinoid acid receptor responder protein 1 in renal cell carcinomas

AIM To evaluate the expression and prognostic value of RARRES1 at protein level in renal cell carcinoma (RCC). MATERIALS & METHODS Expression profile of RARRES1 was analyzed in 903 documented RCC followed by clinicopathological correlations and survival analysis. RESULTS RARRES1 expression was seen in 72.5% of RCC. A stronger RARRES1 expression was seen in high grade compared with low grade RCC (p < 0.001). Logrank tests revealed shorter overall survival in RARRES1 positive RCC (p = 0.006) and in pT1/2 tumors with RARRES1 expression (p = 0.002). CONCLUSION The variable expression profile in low and high grade RCC may reflect and confirm the differences of previous gene expression analysis. There was a significant prognostic value of RARRES1 expression in patients with RCC, especially in pT1/2 tumors.

Inzidenz, Therapie und Prognose kolorektaler Tumoren in verschiedenen Altersgruppen. Eine bevölkerungsbasierte Kohortenstudie des Krebsregisters Rostock

Purpose:Determination of frequency, treatment modalities used and prognoses of colorectal cancer in a population-specific analysis in relation to age.Material and Methods:In 1999 and 2000, 644/6,016 patients were documented as having colorectal carcinomas in the Cancer Registry of Rostock. 39 patients were excluded (16 cases: “in situ” carcinomas; 23 cases: insufficient data). Three age groups were formed: < 60 years, 60–74 years; ≥ 75 years.Results:The relative percentage of colorectal cancer increases with advanced age (< 60 years 7%; 60–74 years 12%, ≥ 75 years 15%; p < 0.001).In older patients with stage III carcinomas, adjuvant treatment was done less frequently in accordance with the treatment recommendations (< 60 years 83–89%; 60–74 years 67–77%; ≥ 75 years 29–36% according to stage and tumor localization); in stage IV, the use of chemotherapy was reduced (< 60 years 87.5–100%; 60–74 years 38–47%; ≥ 75 years 33–37%).In the univariate analysis, age ≥ 75 years (4-year survival rates: < 60 years 68 ± 4.1%; 60–74 years 58 ± 2.8%; ≥ 75 years 38 ± 3.7%), UICC stage and surgical treatment had a significant effect on prognosis. Adjuvant treatment had no significant effect on the whole population but on patients with UICC stage III and IV.In the multivariate analysis, however, the only independent prognostic parameters were age ≥ 75 years (p = 0.001), performance of chemotherapy (colon cancer) or radiochemotherapy (rectal cancer; p = 0.004–0.001), and tumor stage (p = 0.045–0.001). Sex (p = 0.063) and age between 60 and 74 years (p = 0.067) had a borderline influence.Conclusion:With increasing age, there is a departure in daily practice from the treatment recommendations. The patient’s prognosis is dependent upon age (especially ≥ 75 years), tumor stage, and therapy.ZusammenfassungZiel:Bestimmung der Häufigkeit, der Therapiemodalitäten und der Prognose von Patienten mit kolorektalen Tumoren in einer bevölkerungsspezifischen Analyse in Bezug auf das Alter.Material und Methodik:Zwischen 1999 und 2000 wurden im Krebsregister Rostock 644/6 016 Patienten mit kolorektalen Karzinomen dokumentiert. 39 Patienten wurden ausgeschlossen (16 Fälle: In-situ-Karzinome; 23 Fälle: Insuffiziente Daten). Drei Altersgruppen wurden gebildet: < 60 Jahre, 60–74 Jahre, ≥ 75 Jahre.Ergebnisse:Der relative Anteil kolorektaler Karzinome steigt mit zunehmendem Alter (< 60 Jahre 7%; 60–74 Jahre 12%; ≥ 75 Jahre 15%; p = 0,001).Mit zunehmendem Alter wurden im Stadium III die Behandlungen weniger häufig in Übereinstimmung mit den Therapieempfehlungen durchgeführt (< 60 Jahre 83–89%; 60–74 Jahre 67–77%; ≥ 75 Jahre 29–36% gemäß Stadium und Tumorlokalisation); im Stadium IV nahm der Anteil der Patienten, die eine Chemotherapie erhielten, mit zunehmendem Alter ab (< 60 Jahre 87,5–100%; 60–74 Jahre 38–47%; ≥ 75 Jahre 33–37%).In der univariaten Analyse hatten das Alter ≥ 75 Jahre (4-Jahres-Überlebensraten: < 60 Jahre 68 ± 4,1%; 60–74 Jahre 58 ± 2,8%; ≥ 75 Jahre 38 ± 3,7%), das UICC-Stadium und die chirurgische Therapie einen signifikanten Effekt auf die Prognose. Eine adjuvante Behandlung zeigte für das gesamte Kollektiv mit Ausnahme von Patienten im UICC-Stadium III und IV keine signifikante Wirkung.In der multivariaten Analyse sind dagegen nur das Alter ≥ 75 Jahre (p = 0,001); die Durchführung einer Chemotherapie (Kolonkarzinom) oder Radiochemotherapie (Rektumkarzinom; p = 0,004–0,001) und das Tumorstadium (p = 0,045–0,001) unabhängige prognostische Parameter. Ein Alter zwischen 60 und 74 Jahren (p = 0,067) sowie das Geschlecht (p = 0,063) hatten nur einen grenzwertigen Einfluss.Schlussfolgerung:Mit zunehmendem Alter ist in der täglichen Praxis ein Abweichen von den Therapieempfehlungen festzustellen. Die Prognose der Patienten mit kolorektalen Karzinomen ist abhängig vom Alter (insbesondere ≥ 75 Jahre), vom Tumorstadium und von der Therapie.