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BackgroundCorrectly classifying early estrogen receptor-positive and HER2-negative (ER+/HER2) breast cancer (EBC) cases allows to propose an adapted adjuvant systemic treatment strategy. We developed a new AI-based tool to assess the risk of distant relapse at 5 years for ER+/HER2-EBC patients from pathological slides.Patients and MethodsThe discovery dataset (GrandTMA) included 1429 ER+/HER2-EBC patients, with long-term follow-up and an available hematoxylin-eosin and saffron (HES) whole slide image (WSI). A Deep Learning (DL) network was trained to predict metastasis free survival (MFS) at five years, based on the HES WSI only (termed RlapsRisk). A combined score was then built using RlapsRisk and well established prognostic factors. A threshold corresponding to a probability of MFS event of 5% at 5 years was applied to dichotomize patients into low or high-risk groups. The external validation, as well as assessment of the additional prognosis value of the DL model beyond standard clinico-pathologic factors were carried out on an independent, prospective cohort (CANTO,NCT01993498) including 889 HES WSI of ER+/HER2-EBC patients.ResultsRlapsRisk was an independent prognostic factor of MFS in multivariable analysis adjusted for established clinico-pathological factors (pConclusionsOur deep learning model developed on digitized HES slides provided additional prognostic information as compared to current clinico-pathological factors and has the potential of valuably informing the decision making process in the adjuvant setting when combined with current clinico-pathological factors.

Background Pheochromocytomas and paragangliomas (PPGL) are catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla or ganglia and display the highest heritability rate among all human tumours. Genomic analyses allowed identification of molecular subgroups of PPGL which are organized into 2 main clusters. Cluster 1 contains SDHx- and VHL-mutated tumors which do not produce epinephrine while cluster 2 includes the epinephrine-secreting PPGL related to RET, NF1, TMEM127 and MAX mutations. PPGL must be early diagnosed and treated to prevent adrenergic crises which can be life-threatening. Detection of PPGL is particularly important during pregnancy since PPGL are associated with a high risk of either maternal or fetal complications in this context. Reciprocally, pregnancy can favor adrenergic crises in patients with previously undiagnosed or silent pheochromocytoma (PCC). These dangerous events can be triggered by tumor compression resulting from fetus growth, or labor and delivery. However, it is known that surges in plasma catecholamines may also occur during early gestation suggesting that pregnancy may also activate the secretory activity of PPGL through the involvement of non-mechanical factors, such as gestational hormones. Methods In the present study, we report a case of silent PCC revealed in a pregnant woman by life-threatening adrenergic myocarditis occurring at 31 weeks of gestation. Analysis of PPGL susceptibility genes showed the presence of a heterozygous germline RET variant of uncertain significance. The fact that the first symptoms of catecholamine excess had appeared during the first trimester of pregnancy led us to conduct in vitro studies to investigate the effects of estradiol and the pregnancy hormone chorionic gonadotropin (hCG) on epinephrine secretion by cultured cells derived from the resected patient's tumor. Expression of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) was searched for in the tumor and an additional series of 12 PCC by RT-qPCR and immunohistochemistry. LHCGR expression was also analyzed in silico in the PPGL cohorts of the COMETE and The Cancer Genome Atlas (TCGA) databases. Results hCG stimulated epinephrine secretion by primary cultured PCC cells. The tumor expressed the LHCG receptor, which was colocalized with catecholamine-producing enzymes. A similar expression pattern of the LHCG receptor was also observed in 5 out of a series of 12 PCCs. Moreover, in silico studies revealed that PPGL display the highest expression levels of LHCGR mRNA among the 32 solid tumor types of TCGA cohort. Interestingly, expression of LHCGR was higher in cluster 2 than in cluster 1 PPGL. Conclusion We show that PCC can express functional LHCG receptor. Consequently, pregnancy may activate catecholamine production by previously silent pheochromocytoma as early as the first trimester of gestation especially in women with gene mutations that predispose to cluster 2 epinephrine-secreting PCC. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:18 p.m. - 1:23 p.m.

Crustal fault zones provide interesting geological targets for high-temperature geothermal energy source in naturally deep-fractured basement areas. Field and laboratory studies have shown the ability of these systems to let fluid flow down to the brittle–ductile transition. However, several key questions about exploration still exist, in particular the fundamental effect of tectonic regimes on fluid flow in fractured basement domains. Based on poro-elasticity assumption, we considered an idealized 3D geometry and realistic physical properties. We examined a model with no tectonic regime (benchmark experiment) and a model with different tectonic regimes, namely a compressional, an extensional and a strike-slip tectonic regime. Compared to the benchmark experiment, the results demonstrate that different tectonic regimes cause pressure changes in the fault/basement system. The tectonic-induced pressure changes affect convective patterns, onset of convection as well as the spatial extent of thermal plumes and the intensity of temperature anomalies. Driven by poro-elastic forces, temperature anomalies around vertical faults in a strike-slip tectonic regime have a spatial extent that should be considered in preliminary exploratory phases.

Additional file 5: Figure S1. Sample rarefaction curves of alpha diversity indices for bacterial (a) and protists (b) datasets. (PPTX 995 kb)

Nearly complete (> 97%) chloroplast-encoded rbcL gene sequences were determined for Bolidomonas mediterranea from the eastern Mediterranean Sea and two strains of B. pacifica var. eleuthera from the equatorial Pacific Ocean. The three sequences were added to an rbcL data matrix comprising 45 taxa representing 11 of the 12 recognized classes of Hetero-kontophyta. Phylogenetic analyses that used maximum parsimony (MP), maximum likelihood (ML) and neighbour-joining (NJ) algorithms supported their sister group relationship to the Bacillariophyceae. Centric and pennate diatoms and the three novel Bolidomonas rbcL sequences share a two-amino-acid insertion at position 1336, relative to the homologous position in the complete sequence for the centric diatom Odontella sinensis. This synapomorphic character state further supports a common evolutionary history of bolidophyceans and diatoms. Chloroplast- and nuclear-encoded molecular markers thus favour the idea that the ancestor of the diatoms possessed tw...

The presence of tumor cells can be identified in the lymph node when metastasis has occurred from the primary cancer site into the lymph node (1) If the sentinel lymph node ganglion is negative for the presence of tumor cells at the time of histological examination, the other lymph nodes are also negative in 99% of cases. If no tumor cells are identified in the sentinel lymph node ganglion by histological examination, the other lymph nodes are also negative for the presence of tumor cells in 99% of cases. The sentinel lymph node advantageously replaces axillary dissection as a staging method in breast cancer T1 and T2 (2). Approximately 40% of breast cancers metastasize to axillary lymph nodes and metastatic extension depends on disease stage. Sentinel lymph nodes are affected in the following stages: T1a (4.3%), T1b (19.5%), T1c (23.8%), T2 (48.9%), T3 (66.7%).

Fibro-osseous tumor of the digits is an uncommon, benign condition with an excellent prognosis after local excision. Like myositis ossificans, clinical and histological features may mimic a malignant tumour, especially an extraskeletal osteosarcoma. A correct interpretation of clinical, radiological and histological data is a prerequisite to avoid misdiagnosis and unnecessary radical surgery (for example, amputation). We report the case of a 15-year-old boy who presented with a slow-growing mass of the left thumb, which turned out to be a fibro-osseous tumor on microscopic examination. A complete excision was performed without loss of function. Fifteen months postoperatively, there was no local recurrence.

The genus Micromonas comprises distinct genetic clades that commonly dominate eukaryotic phytoplankton community from polar to tropical waters. This phytoplankter is also recurrently infected by abundant and genetically diverse prasinoviruses. Here we report on the interplay between prasinoviruses and Micromonas with regard to the genetic diversity of this host. For 1 year, we monitored the abundance of three clades of Micromonas and their viruses in the Western English Channel, both in the environment using clade-specific probes and flow cytometry, and in the laboratory using clonal strains of Micromonas clades to assay for their viruses by plaque-forming units. We showed that the seasonal fluctuations of Micromonas clades were closely mirrored by the abundance of their corresponding viruses, indicating that the members of Micromonas genus are susceptible to viral infection, regardless of their genetic affiliation. The characterization of 45 viral isolates revealed that Micromonas clades are attacked by specific virus populations, which exhibit distinctive clade specificity, life strategies and genetic diversity. However, some viruses can also cross-infect different host clades, suggesting a mechanism of horizontal gene transfer within the Micromonas genus. This study provides novel insights into the impact of viral infection for the ecology and evolution of the prominent phytoplankter Micromonas.

Wir berichten uber 2 primare synoviale Sarkome der Niere. Die Existenz dieses Tumortyps in der Niere wurde erst vor kurzem erkannt. Bisher wurden 20 Falle publiziert. Wegen der primitiven „embryonalen“ Zellen und der auffalligen zystischen Strukturen wurden diese Tumoren ursprunglich als embryonale zystische Sarkome der Niere bezeichnet. Synoviale Sarkome der Niere treten meist bei 20- bis 50-jahrigen Patienten auf. Eine Zusammenstellung aller publizierten Falle lasst vermuten, dass das Auftreten von Lokalrezidiven nach Nephrektomie haufig ist. Makroskopisch handelt es sich bei den Primartumoren meist um grose (5–15 cm), teilweise nekrotische und haufig zystische Tumoren. Mikroskopisch sind synoviale Sarkome der Niere durch monomorphe, plumpe Spindelzellen charakterisiert. Die Zysten werden durch polygonale eosinophile Zellen ausgekleidet, die keine wesentlichen Zellatypien aufweisen. Die Spindelzellen exprimieren immunhistochemisch Vimentin, CD56, teilweise auch CD99 und EMA, sind aber negativ fur Desmin, Aktin, S 100 und in unseren Fallen fur Zytokeratin. Das Zystenepithel ist Zytokeratin-positiv. In beiden Fallen konnte die fur synoviale Sarkome charakteristische SYT-SSX-Genfusion nachgewiesen werden. Primare synoviale Nierensarkome stellen somit eine neue Tumorentitat der Niere dar, die bei der Differenzialdiagnose von spindelzelligen Tumoren der Nieren berucksichtigt werden muss.

Objective: In this article, we present two case reports. The first case was a malignant germ cell tumor of the right ovary in a 23 year old female and a case of a bilateral undifferentiated granulosa cell tumor in a 71 year old female. The aim of these reports is to illustrate the interest of the immuno-histochemical analysis to define the correct diagnosis, to better classify these ovarian tumours and improve their management. Methods: This study we report two cases. The first case concern a 23 years old woman (A) with a mixed germ cell tumour of the right ovary (dysgerminoma (75%), yolk sac tumour (20%), and a mature teratoma (5%), and the second case (B) a bilateral non differentiated and necrotic granulosa cell tumour of both ovaries concerning a 71 year old patient. The staging system used was according to both classifications, the one of International Federation of Gynaecology and Obstetrics (FIGO) 1987 for ovarian cancer, and the one of TNM code 2009. Results: The immunostaining establish the malignancy and the immunochemistry contribute to confirm effectively the right diagnosis (Table 2 and 3). Conclusion: An immuno-histochemical analysis is mandatory for the choice of chemotherapy to obtain the better response of the disease and improve the survival prognosis. The efficiency of the chemotherapy authorizes a conservative surgery including a unilateral salpingo-oophorectomy preserving fertility (A). Concerning the non-dysgerminoma tumour (B), and after a surgical staging and debulking, chemotherapy was recommended. The type of tumour and its histological feature conditioned the choice of treatment. The benefit of the immunohistological analysis in this case allowed the right adjuvant treatment. Key words: germ cell tumours, dysgerminoma, teratoma, yolk sac, ovarian cell tumour, and immunohistochemistry.

Summary This report describes a case of unusual intraductal “clear cell” changes of male breast that mimicked pagetoid ductal spread of lobular neoplasia. The lesion developed inside a nodule of gynecomastia of the left breast in a 56 year-old man. Immunohistochemically, the enlarged clear cells reacted positively with epithelial membrane antigen, low molecular weight cytokeratin and three breast markers (i.e.: gross cystic disease fluidprotein-15 and -44 and estrogen receptors). They were negative for high molecular weigh cytokeratin, muscle-specific actin, desmin and vimentin. Differential diagnoses included pagetoid ductal involvement by lobular neoplasia (i.e.: lobular carcinoma in situ and/or atypical lobular hyperplasia), pagetoid growth of intraductal carcinoma, atypical intraductal hyperplasia, and unusual intraductal myoepithelial proliferative lesion.

The toxicity of an organic titanium salt, titanium diisopropoxide bis (2–4 pentanedionate) was tested in rats and mice. After acute oral intoxication this compound is poorly absorbed and titanium is slowly eliminated in the faeces. After acute inhalation of an oily aerosol of the compound, faecal excretion is more important than urinary elimination but the latter is significantly higher than after oral administration. Irritation of mucous membranes and pulmonary difficulties are the major clinical signs of the intoxication. Repeated inhalation (6 hours per day, 5 days per week) over 4 weeks leads to an important pulmonary deposit. Later on, because of its ability to combine with tissue proteins, the titanium accumulated in the lungs slowly diffuses and remains for a long time in the body. Titanium toxicity was also demonstrated in primary rat hepatocyte cultures. IC50 values for the four tests used were closed to 65 μg ml−1. Therefore comparison of these in vitro results with the in vivo data appears diff...

Blastodinium are chloroplast-containing dinoflagellates which infect a wide range of copepods. They develop inside the gut of their host, where they produce successive generations of sporocytes that are eventually expelled through the anus of the copepod. Here, we report on copepod infections in the oligotrophic to ultra-oligotrophic waters of the Mediterranean Sea sampled during the BOUM cruise. Based on a DNA-stain screening of gut contents, 16% of copepods were possibly infected in samples from the Eastern Mediterranean, with up to 51% of Corycaeidae, 33% of Calanoida, but less than 2% of Oithonidae and Oncaeidae. Parasites were classified into distinct morphotypes, with some tentatively assigned to species B. mangini, B. contortum, and B. cf. spinulosum. Based upon the SSU rDNA gene sequence analyses of 15 individuals, the genus Blastodinium was found to be polyphyletic, containing at least three independent clusters. The first cluster grouped all sequences retrieved from parasites of Corycaeidae and Oncaeidae during this study, and included sequences of Blastodinium mangini (the "mangini" cluster). Sequences from cells infecting Calanoida belonged to two different clusters, one including B. contortum (the "contortum" cluster), and the other uniting all B. spinulosum-like morphotypes (the "spinulosum" cluster). Cluster-specific oligonucleotidic probes were designed and tested by FISH in order to assess the distribution of dinospores, the Blastodinium dispersal and infecting stage. Probe-positive cells were all small thecate dinoflagellates, with lengths ranging from 7 to 18 μm. Maximal abundances of Blastodinium dinospores were detected at the Deep Chlorophyll Maximum (DCM) or slightly below. This was in contrast to distributions of autotrophic pico- and nanoplankton, microplanktonic dinoflagellates, and nauplii which showed maximal concentrations above the DCM. The distinct distributions of dinospores and nauplii argues against infection during the naupliar stage. Blastodinium, described as autotrophic in the literature, may escape the severe nutrient limitation of ultra-oligotrophic ecosystems by living inside copepods.

Sequences affiliated to Syndiniales (Marine alveolate, MALV) regularly dominate 18S rDNA genetic libraries of nearly all marine ecosystems investigated so far. Among them, Amoebophryidae (MALV group II) is composed of numerous and genetically distant environmental sequences, where Amoebophrya is the only known and formally described genus. Amoebophrya species include virulent pathogens for a wide range of dinoflagellate species. Beside their regular occurrence in marine ecosystems, their quantitative distribution and the environmental factors triggering host infection have barely been studied in open oligotrophic waters. In order to understand the functional role of these parasites in natural environments, we studied the distribution and contribution to the eukaryotic community of the small free-living stage of Amoebophryidae (the dinospores) along a transect in the Mediterranean Sea, as well as their host diversity at three oligotrophic stations. Dinospores were more abundant at a coastal station (max. 1.5 × 103 cells ml−1) than in oligotrophic waters (max. 51 ± 16.3 cells ml−1), where they represented 10.3 to 34.9% of the total eukaryotic community at 40 and 30 m depth, respectively and 21.2% on average along the water column. Positive correlation was found between dinospore occurrence and higher concentration of NO3 + NO2 at the coastal station. At selected stations, out of 38 different dinoflagellates taxa identified, 15 were infected, among which a majority were not recognized as Amoebophryidae host so far. Prevalences (percentage of infected cells) generally varied between 2% and 10%, with a notable exception for Blepharocysta paulsenii for which 25% of cells were infected at the station C. The present study shows that dinospores are able to thrive, infects and most probably exert a control on host populations both in coastal and ultra-oligotrophic open waters. Our results emphasize the role of parasitism in microbial food web dynamics and ultimately on biogeochemical cycles.

Resume Introduction Les auteurs rapportent le cas d'un patient souffrant de fessalgies invalidantes survenant en plongee. Synthese des faits Le diagnostic de pneumatokyste osseux de l'aile iliaque est realise par tomodensitometrie. La lesion est traitee par ponction et comblement par une substance inerte sous controle radioscopique. Levolution est favorable. Conclusion Il s'agit a notre connaissance de la deuxieme observation revelee par une symptomatologie douloureuse chez un plongeur et du premier cas traite par radiologie interventionnelle.

We report a case of renal metastases from prostate cancer to show that the possibility of tumor metastasis, although rare, should always be considered in the differential diagnosis of renal mass.

Fibro-osseous tumor of the digits is an uncommon, benign condition with an excellent prognosis after local excision. Like myositis ossificans, clinical and histological features may mimic a malignant tumour, especially an extraskeletal osteosarcoma. A correct interpretation of clinical, radiological and histological data is a prerequisite to avoid misdiagnosis and unnecessary radical surgery (for example, amputation). We report the case of a 15-year-old boy who presented with a slow-growing mass of the left thumb, which turned out to be a fibro-osseous tumor on microscopic examination. A complete excision was performed without loss of function. Fifteen months postoperatively, there was no local recurrence.

Smart cards are introduced through chip design, card interface, and card security. Applications are divided in three classes : log books, certified records, key carriers.Conditional acces is analyzed with a clear distinction between entitlement checking and entitlement management. The key carrier CP8 card is then described. Smart card cryptology is examined, and also the probable evolution towards digital signatures.

Summary This case report concerns a 64 year-old woman who presented a pathologic fracture of the femur neck. Histologic examination of the performed bone biopsy disclosed the presence of a carcinomatous metastasis with unusual microscopic features. The site of the primary tumor could be unequivocally determined as being the thyroid gland, as immunostaining of the tumor cells showed positivity with anti-thyroglobulin. The thyroidectomy specimen weighed 149 g, was nodular and partially calcified. Exhaustive microscopic examination finally revealed the presence of a minute columnar cell carcinoma, 0.6 em in diameter, with obvious vascular invasion. This case illustrates well 1) the usefulness of immunostaining with anti-thyroglobulin in cases of bone metastasis with unusual microscopic features and unknown primary, as well as 2) the aggressiveness of this rare type of carcinoma of the thyroid.

Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

This article reviews the clinicopathologic features and differential diagnoses of 7 newly described adipocytic lesions: chondroid lipoma, myolipoma, lipomatous hemangiopericytoma, sclerotic lipoma, fibrohistiocytic lipoma, hemosiderotic fibrohistiocytic lipomatous lesion, and spindle cell liposarcoma. Two recently described variants of spindle cell/pleomorphic lipoma are also presented: the pseudoangiomatous variant and the dendritic fibromyxolipoma, which corresponds in all likelihood to a peculiar myxoid variant of spindle cell lipoma.

Previous studies showed that injections of somatostatin (SS-14) into the hippocampus facilitate the acquisition of spatial tasks in mice. The present study was aimed at better understanding the learning and memory processes that could be affected by hippocampal SS-14 stimulation. Balb/c mice were submitted to a two-stage learning paradigm. In stage 1, they were trained for acquisition of a spatial discrimination task in a radial maze and, in stage 2, were submitted to a probe test aiming at evaluating their ability to use flexibly their previously acquired knowledge. Injections of vehicle or SS-14 were given during the acquisition phase and/or before the probe test using a 2 x 2 factorial design. Mice receiving SS-14 during acquisition failed to succeed in the probe test despite showing a trend to faster acquisition of the initial spatial discrimination task. By contrast, when given only prior to probe trials, SS-14 did not yield any behavioural effects. Thus, SS-14 interfered with the establishment of a flexible form of memory, not with its expression per se, and therefore dissociated the acquisition of place responses from their flexible use. The theoretical issues raised by the present findings are discussed.

We report a rare case of benign granular cell tumor of the breast associated with multiple similar lesions of the scalp, the right shoulder, the right flank, the abdominal wall and the vulva, treated with wide excisions.

Synovial sarcoma (SS) is a relatively rare sarcoma, which may be confused with several other mesenchymal and nonmesenchymal lesions. It bears the t(X;18) (SYT;SSX) translocation, which seems to be specific for this tumor type and can be detected in paraffin-embedded tissue, using reverse transcriptase-polymerase chain reaction (RT-PCR). However, the specificity and sensitivity of this detection method have rarely been examined in a large series. Using RT-PCR, we examined 250 mesenchymal and nonmesenchymal, benign and malignant, paraffin-embedded lesions for the SS t(X;18) (SYT-SSX) translocation. PCR products were obtained from 221 tumors (88.5%). There were 135 non-SS tumors, 22 biphasic, and 64 monophasic spindle/round cell SS, of which 10 were cytogenetically confirmed as t(X;18)-positive. SYT-SSX gene fusion transcripts were detected in the SS tumor category only (100% specificity), including 100% of the biphasic SS and 86% of monophasic spindle/round cell SS. Nine tumors originally diagnosed as SS were t(X;18) (SYT-SSX)-negative. Following reassessment, only 3 of these tumors showed clinicopathologic, immunohistochemical, and/or ultrastructural features consistent with that diagnosis, thus raising the overall detection sensitivity to 96%. With regard to the potential adverse effect of the fixatives used, PCR products were obtained in 100%, 91.5%, 90.5%, and 0% of tumors fixed with AFA, buffered formalin, Holland Bouin, and conventional Bouin's fluid, respectively. This study shows that the detection of the SS t(X;18) (SYT-SSX) in paraffin-embedded tissue is feasible with a 100% specificity and an overall 96% sensitivity, provided non-Bouin's fluid fixation is used.

The effects of continents on mantle heat flow are explored through a synthesis of heat flow data analysis and theoretical modeling. The data employed are from the Canadian Shield and the Canadian Appalachians and consist of both surface heat flow measurements and measurements of crustal heat production. The combined data sets, together with gravity and seismic information, which is used to help constrain crustal structure and composition, suggest that the mantle component of surface heat flow is low, between 10 and 15 mW/m 2 , and relatively uniform across a large portion of central to eastern Canada. Surface heat flow variations across the region covered can be well accounted for by observed variations in crustal heat production, i.e., no mantle heat flow variations need to be invoked. Laboratory experiments and numerical simulations, that explore the coupling between continents and the convecting mantle from a modeling based point of view, show how large, buoyant continents can locally constrain heat flux variations in the mantle below. Relative to what occurs in model oceanic regions, the equilibrium thermal condition imposed on the mantle by model continents is one of low and nearly uniform heat flux. Such a condition is consistent with the inferences drawn from the Canadian heat flow data. Theoretical models also imply that the local thermal constraint imposed on the mantle by continents can cause mantle heat flow to be relatively weakly correlated with tectonic age variations, lithospheric thickness variations, and local mantle flow patterns below tectonothermally stable continental regions.

Telomerase activity (TA) is detected in most human cancers but, with few exceptions, not in normal somatic cells. Little is known about TA in soft tissue tumors. We have examined a series of benign and malignant soft tissue tumors for TA using the telomerase repeat amplification protocol assay. Analysis of the expression of the human telomerase reverse transcriptase was also carried out using RT-PCR. TA was undetectable in benign lesions (15 of 15) and low-grade sarcomas (6 of 6) and was detectable in 50% (19 of 38) of intermediate-/high-grade sarcomas. Although the presence of TA in soft tissue tumors is synonymous with malignancy, it is neither a reliable method in making the distinction between reactive/benign and malignant (especially low-grade) lesions nor a reliable marker of tumor aggressiveness. Leiomyosarcomas and storiform/pleomorphic malignant fibrous histiocytomas rarely showed TA, irrespective of their grade. A strong correlation between human telomerase reverse transcriptase mRNA expression and TA was observed, supporting the close relationship between both parameters. No significant relationship was observed between proliferative activity (as assessed by MIB-1 immunolabeling) and TA. We verified that the absence of telomerase expression was not due to the presence of telomerase inhibitors and therefore alternative mechanism(s) for cell immortalization, yet to be determined, seem to be involved in the development and/or maintenance of some soft tissue sarcomas.

Sporadic renal cell carcinomas (RCCs) display different chromosomal abnormalities according to their morphology; gains of chromosomes 7 and 17 and loss of Y are commonly observed in papillary lesions, whereas loss of 3p sequences and multiple losses of specific chromosomes are found in non-papillary and chromophobe cell carcinomas, respectively. Acquired renal cystic disease (ARCD) is associated with an increased incidence of renal cell tumours, especially papillary lesions. The aim of this study was to examine a series of ARCD-related tumours for chromosomal abnormalities and to compare the findings with those abnormalities commonly observed in sporadic RCCs. Nine tumours from four patients with ARCD were examined using comparative genomic hybridization (CGH) and interphase cytogenetics. Gain of chromosomes 7 and 17 was observed in all four papillary lesions and loss of Y in three. In addition, gain of chromosome 16 was observed in three papillary tumours. Three chromophobe RCCs originating from the same kidney showed different genomic profiles; two had no abnormalities, whereas one showed loss of chromosome 17p. Two non-papillary RCCs failed to show chromosome 3p alterations. In conclusion, renal cell tumours developing in ARCD may show chromosomal abnormalities both similar to and different from those seen in sporadic tumours.

CD95/APO-1 ligand (FasL) is implicated in the maintenance of immune privileged sites by inducing apoptosis of activated infiltrating T lymphocytes. Therefore, progressive tumors might express high levels of FasL and develop as immune privileged sites. In this study, we investigated the expression of FasL and CD95/APO-1 (Fas, the FasL-receptor) in vitro in rat adenocarcinoma cell lines and the localization in situ in normal human kidney and colon and in their adenocarcinomas. The rat cell line PROb (a progressive tumor in vivo) expressed a higher level of FasL than the sister cell line REGb (a regressive tumor in vivo), as detected by flow cytometry. The 2 cell lines expressed the same level of Fas, but were resistant to FasL-induced apoptosis. In human tissue, both kidney and colon extracts expressed FasL by Western blot. Further investigations, using immunohistochemical staining of paraffin sections, showed that normal colon mucosa expressed Fas and FasL in crypt epithelial cells in the subnuclear compartment. Normal kidney showed Fas and FasL labeling mostly restricted to epithelial cells of proximal tubules and Henlé's loop, showing that this expression is not uniform throughout the organ. Smooth-muscle cells of muscularis propria and blood vessels in and around the tumors were also intensely but more uniformly labeled. In colon-cancer cells, FasL expression remained strong, whereas Fas expression was significantly reduced. A similar reduction in Fas expression was noted in renal-cancer cells. Tumor-infiltrating immune cells of the macrophage lineage do not express FasL. Our results show that smooth-muscle cells of muscularis propria and blood vessels are able to express FasL and to a slight extent Fas. In normal epithelial cells of colon and kidney, Fas and FasL are often co-expressed. The reduced expression of Fas in corresponding cancer cells in combination with the ability to express FasL might facilitate immune escape.