Incidence of skin lymphoma in Germany.

PURPOSE: Population-based analyses of the incidence of skin lymphoma in Europe are very sparse. We analyzed German population-based incidence data on skin lymphoma to study the descriptive epidemiology of these tumors. METHODS: We extracted skin lymphoma cases from the registry files of the East German National Cancer Registry (1976-1989) and registries of three new federal states (1998-2002) (Sachsen, Brandenburg, Mecklenburg-Vorpommern), the Cancer Registry Schleswig-Holstein, Lübeck (1998-2002), and the Epidemiological Cancer Registry Münster (1998-2002). We calculated age-standardized incidence rates (world standard population) and compared these figures with international data. RESULTS: From 1976 through 1989, 619 cases of skin lymphoma were registered in the former German Democratic Republic. During this period, the incidence among men increased from 2.0 to 2.5 per million and decreased among women from 1.5 to 0.8 per million. Current age-standardized incidence rates of skin lymphoma (1998-2002) varied by sex and registry and were about 3.2-6.0 per million among men and 1.6-2.6 per million among women. CONCLUSIONS: The current incidence rates among the registries of Germany are fairly similar but are considerably lower than incidence rates from the United States and Israel. Several methodological issues hamper the analysis of population-based incidence data of skin lymphoma.

Population-based incidence rates of malignant melanoma of the vulva in Germany.

OBJECTIVES: Only few population-based incidence analyses of vulvar melanoma including the United States and Sweden are currently available. We studied the incidence of vulvar melanoma in a large population-based cancer registry of East Germany and compared our findings with the United States and Sweden. METHODS: We extracted vulvar melanoma registered between 1976 and 1989 in the former National Cancer Registry of the German Democratic Republic (GDR) and of three new East German cancer registries of the federal states of Sachsen, Brandenburg, and Mecklenburg-Vorpommern of the period 1998 to 2002. We calculated age-specific and age-standardized incidence rates using the World Standard Population. RESULTS: One hundred two cases (1976-1989, former GDR) and twenty-five cases of vulvar melanoma (1998-2002, three new federal states) were registered. The age-standardized incidence rate (World Standard Population) remained constant over the period from 1976 to 1989 and ranged between 0.26 and 0.52 cases per million. From 1998 to 2002, the incidence rate was 0.48 per million. The ratio of registered vulvar melanoma to skin melanoma was 1:71, and the ratio of vaginal melanoma to skin melanoma was 1:314. Age at diagnosis during the period 1976 to 1989 was lower among women with vulvar melanoma (median age 70 years) compared to women with vulvar tumors other than melanoma (median age 73 years). CONCLUSIONS: The risk of vulvar melanoma was considerably lower in East Germany than in the United States and Sweden. Due to the rarity of vulvar melanoma, population-based cancer registries are hampered to study this tumor in detail.

[The importance of the common cancer registry for the identification of cancer cases in the EPIC Potsdam-study -- results of the first record linkage]. / Die Rolle des Gemeinsamen Krebsregisters bei der Identifizierung von Krebsfällen in der EPIC-Potsdam-Studie -- Ergebnisse des ersten Datenabgleichs.

AIM: The follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study has been identifying cancer diagnoses by an active follow-up through participant's self-report which is then confirmed by pathology registries or medical doctors. To utilise another source of information, a record linkage was performed with the Common Cancer Registry (CCR) of the states of Berlin, Brandenburg, Mecklenburg-Western Pomerania, Saxony-Anhalt and of the free states Saxony and Thuringia in November 2001, using the EPIC-Potsdam database of compliant study participants at that point in time (n = 27 087). This methodological study compares data of identified cancer cases in the EPIC-Potsdam study with those generated through the record linkage. METHODS: The GKR identified 1468 study participants of the EPIC-Potsdam study. Cases (n = 108) with non-melanoma skin cancer were excluded. A separate analysis was done for prevalent (date of cancer diagnosis before baseline examination) and incident cancers (date of diagnosis after baseline examination). We examined how many subjects with at least one cancer were known to EPIC-Potsdam and the CCR, how many had been known only to the CCR and how many only to the EPIC-Potsdam study. Of incident cancer cases each diagnosis was counted. It was analyzed whether the diagnoses as they had been collected by EPIC-Potsdam were identified by the record linkage. Focus was on the diagnoses that had been unknown in EPIC-Potsdam before. The concordance of information from both sources was also considered. RESULTS: According to the record linkage, 1298 subjects with at least one prevalent cancer were identified in the EPIC-Potsdam cohort, 593 (46 %) of whom were identified in both data sources, 241 (19 %) were newly identified, and 464 (36 %) participants self-reported at least one prevalent tumour which was not identified through the record linkage. Seven tumours were diagnosed before 1961 (the CCR's computerised data are only available since 1961). Fifty-seven percent (n = 187) of all tumours which could not be identified in the cancer registry dated from 1990 - 1995. After completion of the record linkage a total of 582 medically verified incident cancer cases were identified. These comprised 397 medically verified cases that were identified in the EPIC-cohort study prior to the record linkage, 18 self-reported cases where the medical verification was pending, and 167 newly identified cases. Eighty-five of the latter cases have not been identified by other sources in the two following years after record linkage indicating that 15 % of the medically verified cases have been found solely through the linkage. CONCLUSION: The EPIC-Potsdam study had a significant benefit of the record linkage due to both the additional identification and verification of prevalent and incident cancer cases, as well as a timely advanced identification of incident diagnoses. The record linkage with the cancer registry improved the quality of the endpoint data of the EPIC-Potsdam study.

Significance of apoptosis in the process of tumorigenesis in colorectal mucosa and adenomas in FAP patients.

The relation between proliferation and apoptosis was studied in colorectal mucosal biopsies (N = 41), tubular adenomas (TA) (N = 104) and tubulovillous adenomas (TVA) (N = 34) from 37 FAP patients. Proliferative activity was determined by cell cycle distribution analysis. In addition, transcriptional capacity was determined by chromatin in situ testing. For both, DNA flow cytometry was used. Cycling cells were identified by immunohistochemical staining with monoclonal antibody Ki67. The existence of subdiploid apoptotic cells was derived from DNA and/or DNA/protein patterns. In a follow-up group, the mucosa is characterised by a balance between proliferation (S % + G2M % = 19) and apoptotic cells (% = 17). The percentage of Ki67 positive cells (16%) corresponds to the percentages mentioned above. In TA, the amount of apoptotic cells remains unaltered, in TVA it decreases to 8%. At the same time, the percentage of Ki67 positive cells increases significantly in both TA and TVA (39%, 42%). With patients who underwent surgery due to clinical signs without histological evidence for malignancy, apoptotic cells in TA continue to decrease significantly (9%), without any changes in cycling cells. Only in the carcinoma-bearing bowel, cycling cells increase to 52%. Here, the percentage of apoptotic cells in TVA reaches the lowest level (5%). A connection between proliferation and apoptosis was observed in mucosa and TVA. The process of tumorigenesis is characterised by a stepwise increase in resistance to apoptosis followed by an increase in cycling cells.

Cytokinetic investigations in human breast cancer by flow cytometrically recorded DNA/protein distributions.

This prospective study characterizes T1-T2 breast carcinomas (N = 114) and fibroadenomas (N = 16) by cell kinetic parameters derived from flow cytometrically recorded DNA/protein histograms. Ploidy level, cell cycle distribution and the number of cell subpopulations (SP) characterized by correlating DNA and protein values were assessed. The subpopulations were derived from the three-dimensional plot. The estrogen receptor (ER) status was determined biochemically (N = 61). Within the G1/0 cell peak 1-6 SP were evident in principle. Depending on the number of SP, two subsets were established: subset 1 with < or = 2 SP, subset 2 with > or = 3 SP. They differed significantly in proliferative activity expressed in the percentage of cells in the G2M phase. Subset 2 showed the higher activity. Analysis of subset distributions revealed that subset 1 prevails in favourable prognostic cases as ER positive cases (P < 0.03), lobular carcinomas (P < 0.01) and LN- cases (P < 0.03), whereas subset 2 prevails in the unfavourable counterparts. Analysis of variance showed that the main effect on proliferative activity indicated by G2M% is due to subpopulation composition rather than histologic type, nodal status or ER status (P < 0.01, P < 0.002, P < 0.05), not even due to ploidy level (P < 0.0001). The rationale for subset stratification may be cytogenetic variability connected with protein content heterogeneity accounting for kinetic SP.

DNA distributions in human normal, precancerous and cancerous breast tissue. II. Differences in heparin mediated changes in DNA distributions.

DNA distributions were recorded flow cytometrically (FCM) in human normal, precancerous (P1 characterized by ductal hyperplasia and/or lobular hyperplasia, and P2 characterized by carcinomata lobularia in situ and intraductal carcinoma) and malignant breast tissues. Heparin, a polyanion, mediated two changes: (a) a time-dependent increase in fluorescence intensity (IFI) considered to be inversely proportional to the proliferative activity. IFI was significantly lower in carcinomas than in P2, in normal and in P1 tissues; it identified a highly and a poorly heparin-sensitive subgroup of carcinomas, which differed in respect to histological type and tumor stage distribution; (b) a time-dependent increase in the percentage of recorded DNA aneuploid cells (IAC) at the expense of DNA diploid cells in mixed cell population. IAC is considered to correspond to cell membrane permeability. DNA aneuploid cell populations homogeneous in respect to DNA - index (DI) seem to be heterogeneous in respect to cell membrane function. Duct carcinomas showed significantly higher IAC than lobular carcinomas.

DNA ploidy and proliferation characteristics of bowel polyps analysed by flow cytometry compared with cytology and histology.

56 human adenomatous bowel polyps and 44 samples of macroscopically unchanged bowel mucosa taken at a distance of 2-10 cm from the polyp were investigated by histology, cytology, and flow cytometry in respect to their dysplasia grade and DNA distributions. 30 human adenomatous polyps of the same localization were investigated by histology and flow cytometry; in 14 cases in addition to the DNA-patterns per se their changes mediated by heparin, a polyanion, were recorded. Histological and cytological investigations revealed mild dysplasia in 25 cases, moderate dysplasia in 43 cases and severe dysplasia in 18 cases. DNA aneuploidy was correlated with the histological finding of mild dysplasia three times, of moderate dysplasia twice and severe dysplasia five times. All other cases, also macroscopically unchanged bowel mucosa revealed DNA diploidy. In these diploid cases, cell cycle stage analysis yielded a higher proportion of cells in S-phase and G2M phase in adenomas with severe dysplasia in comparison to adenomas with moderate and mild dysplasia (P less than 0.05). Macroscopically unchanged bowel mucosa showed about the same values as adenomas with mild dysplasia. The heparin mediated increase in fluorescence intensity is different for adenomas with mild and moderate dysplasia, and attributed to the latter a higher proliferative activity (P less than 0.05).

DNA distributions in human normal, precancerous and cancerous breast tissue. I. Ploidy and cell cycle distribution.

DNA distributions were recorded flow cytometrically in 19 normal, 23 precancerous tissues with epithelial proliferation and cell atypia (P1), 7 carcinomata lobularia in situ and intraductale carcinomas (P2) and in 44 invasive carcinomas of the human breast. The results were compared to histological findings, tumor staging and grading, lymph node involvement and age of the patients. DNA diploidy was found in all normal, 21 P1 tissues, 6 P2 tissues and 12 carcinomas; DNA aneuploidy in 2 P1 tissues, 1 P2 tissue and 32 carcinomas. Lobular carcinomas were preferentially involved in the DNA diploid group, duct carcinomas in the DNA aneuploid group. Cell cycle distribution analysis resulted in significantly higher percentages of cells in S- and G2M phase in DNA aneuploid carcinomas compared to normal and precancerous (P1, P2) tissues. The percentage of cells in G2M phase was significantly higher in DNA aneuploid carcinomas originating from patients younger than 50 years compared to patients older than 50 years. Correlations between the DNA-index, cell cycle distribution, lymph node involvement, tumour staging or histological type were not evident.

[The determination of the oncolytic effect of clostridia with the hamster amelanotic Melanoma no.3--a quantitative study utilizing defined criteria of evaluation (author's transl)]. / Bestimmung der onkolysierenden Wirkung von Klostridien am Hamster-A Mel 3-Modell--eine quantitative Studie mit definierten Bewertungskriterien.

With a view of satisfying the practical demands on a diagnostic tumour clostridium assay the development of a biological tumour test model is of prime importance. We are interested in a safe method for differentiating between oncolytic clostridia and clostridial strains exerting no oncolytic capacity. It was therefore attempted to develop a reproducible assay system using hamster A-Mel-3 as a reference tumour. This was finally attained by quantifying oncolysis taking into account the criterium of spontaneous onconecrosis of this tumour. The proposed oncolytic assay system was submitted to a mathematical regression analysis using different strains of clostridia as well as different batches of cultivated spores of one and the same strain. The results are critically compared with the current literature.