Pleuramesotheliom: Zytologie und molekulare Diagnostik

Zusammenfassung: Die definitive Diagnose eines malignen Mesothelioms (MM) in der Ergusszytologie wird oft nicht oder nur sehr zurückhaltend gestellt. Dieser Skeptizismus dürfte v.a. auf die mangelnde zytologische Expertise vieler Pathologen und Kliniker zurückzuführen sein. Bei eindeutigen Malignitätszeichen und immunzytochemisch gesichertem mesothelialem Immunphänotyp ist die Diagnose eines MM in der Ergusszytologie durchaus möglich. Im Falle unklarer, atypischer mesothelialer Zellen kann eine definitive morphologische Diagnose allerdings schwierig und eine weitere Abklärung mit Zusatzmethoden nötig sein. MM weisen im Gegensatz zu reaktiven Mesothelien häufig chromosomale Aberrationen auf, am häufigsten eine Kombination aus Polysomie und 9p21-Deletion. Diese lassen sich gleichzeitig mittels Mehrfach-Fluoreszenz-in-situ-Hybridisierung (FISH) nachweisen. Bei der Abgrenzung eines MM von einem Adenokarzinom hat sich ein immunzytochemisches Panel aus mesothelialen und epithelialen Markern bewährt. In den meisten Fällen mit unklaren atypischen Mesothelien ist somit unter Berücksichtigung der Morphologie, Immunzytochemie und FISH eine zuverlässige Unterscheidung zwischen reaktiven Mesothelien und MM an der Ergusszytologie möglich

Incidental prostate cancer prevalence at radical cystoprostatectomy—importance of the histopathological work-up

The reported incidental prostate cancer prevalence rates at radical cystoprostatectomy cover a range from 4 to 60%. We investigated the influence of the histopathological work-up on prostate cancer prevalence rates. We identified 114 patients who had undergone cystoprostatectomy for bladder cancer between 2000 and 2012. Complete histopathological assessment was defined as follows: (i) complete embedding of the prostate gland, (ii) sectioning of 15 or more prostate sections, and (iii) processing as whole mount slides. Prostate cancer prevalence rates derived from complete and incomplete histopathological assessments were compared. The overall prostate cancer prevalence rate was 59.6%. A mean of 14.4 macroscopic tissue sections (thickness 3-5mm) were sectioned. Sectioning ≥15 sections resulted in a prostate cancer detection rate of 75%, compared to 42.6% when sectioning <15 sections (p < 0.001). Complete embedding yielded a prostate cancer detection rate of 72.3 and of 23.1% for partly embedded prostates (p < 0.0001). Prostate cancer was detected in 68.8% of the whole mounted samples and in 38.2% of the samples sectioned as standard slides (p < 0.01); according to the criteria described by Epstein and Ohori, 44.1% of the detected prostate cancers were clinically significant. The quality of the histopathological work-up significantly influences prostate cancer detection rates and might at least partially explain the highly variable reported incidental prostate cancer prevalence rates at cystoprostatectomy (CP). The high proportion of significant prostate cancer found in our series calls for a careful surgical approach to the prostate during CP

Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients

In colorectal cancer, tumor budding at the invasive front (peritumoral budding) is an established prognostic parameter and decreased in mismatch repair-deficient tumors. In contrast, the clinical relevance of tumor budding within the tumor center (intratumoral budding) is not yet known. The aim of the study was to determine the correlation of intratumoral budding with peritumoral budding and mismatch repair status and the prognostic impact of intratumoral budding using 2 independent patient cohorts. Following pancytokeratin staining of whole-tissue sections and multiple-punch tissue microarrays, 2 independent cohorts (group 1: n = 289; group 2: n = 222) with known mismatch repair status were investigated for intratumoral budding and peritumoral budding. In group 1, intratumoral budding was strongly correlated to peritumoral budding (r = 0.64; P &lt;.001) and less frequent in mismatch repair-deficient versus mismatch repair-proficient cases (P =.177). Sensitivity and specificity for lymph node positivity were 72.7% and 72.1%. In mismatch repair-proficient cancers, high-grade intratumoral budding was associated with right-sided location (P =.024), advanced T stage (P =.001) and N stage pN (P &lt;.001), vascular invasion (P =.041), infiltrating tumor margin (P =.003), and shorter survival time (P =.014). In mismatch repair-deficient cancers, high intratumoral budding was linked to higher tumor grade (P =.004), vascular invasion (P =.009), infiltrating tumor margin (P =.005), and more unfavorable survival time (P =.09). These associations were confirmed in group 2. High-grade intratumoral budding was a poor prognostic factor in univariate (P &lt;.001) and multivariable analyses (P =.019) adjusting for T stage, N stage distant metastasis, and adjuvant therapy. These preliminary results on 511 patients show that intratumoral budding is an independent prognostic factor, supporting the future investigation of intratumoral budding in larger series of both preoperative and postoperative rectal and colon cancer specimens. © 2011 Elsevier Inc. All rights reserved

VEGFA gene locus (6p12) amplification identifies a small but highly aggressive subgroup of colorectal patients

The aim of this study was to determine: (1) the frequency of VEGFA gene locus (6p12) amplification in colorectal cancers, (2) the effect of gene amplification on clinical outcome using two independent colorectal cancer patient cohorts and (3) the relationship between amplification and KRAS or BRAF gene mutation as well as with other RAS/MAPK signalling proteins. Single-punch (n1280; cohort 1) and multiple-punch (n195; cohort 2) tissue microarrays were used for dual-labelling fluorescence in situ hybridization (FISH). Amplification was defined as a ratio 2 times for 6p12/centromere 6 signals. Mutation analysis of KRAS (codons 12 and 13) and BRAF (codon V600E) and immunohistochemistry for p-MAPK3/MAPK1, PEBP1, HMMR, p-AKT, PLAU, PLAUR, TP53 and VEGFA were performed on cohort 1. In cohort 1, VEGFA amplification was found in 39/1280 (3%) cases and linked to higher pT stage (P0.022), higher tumor grade (P0.024) and vascular invasion (P0.003). The 5-year disease-specific survival rates were 31% (95% CI 17-46) and 57% (95% CI 54-60) for amplified and nonamplified cases, respectively (P0.001). Results were confirmed in cohort 2. In multivariable analysis, the relative risk for amplification was 2.09 (95% CI 1.4-3.1; P0.001) and linked to more frequent BRAF mutation (P0.015), overexpression of p-MAPK3/MAPK1 (P0.012) and PLAU (P0.048) and loss of metastasis suppressor protein PEBP1 (P0.047). VEGFA gene locus amplification highlights a small but remarkably aggressive subgroup of colorectal cancers. Further studies are needed to elucidate the potential role of amplification as a prognostic or predictive biomarker in both metastatic and nonmetastatic patients. © 2011 USCAP, Inc. All rights reserved

Note: Determination of effective gas diffusion coefficients of stainless steel films with differently shaped holes using a Loschmidt diffusion cell

In this work, an in-house made Loschmidt diffusion cell is used to measure the effective O\u2082\u2013N\u2082 diffusion coefficients through four porous samples of different simple pore structures. One-dimensional through-plane mas diffusion theory is applied to process the experimental data. It is found that both bulk diffusion coefficient and the effective gas diffusion coefficients of the samples can then be precisely determined, and the measured bulk one is in good agreement with the literature value. Numerical computation of three-dimensional mass diffusion through the samples is performed to calculate the effective gas diffusion coefficients. The comparison between the measured and calculated coefficient values shows that if the gas diffusion through a sample is dominated by one-dimensional diffusion, which is determined by the pore structure of the sample, these two values are consistent, and the sample can be used as a standard sample to test a gas diffusion measurement system.Peer reviewed: YesNRC publication: Ye