Bone marrow angiogenesis and its correlation with other disease characteristics in multiple myeloma in stage I versus stage II-III.

PURPOSE: We studied bone marrow angiogenesis in different stages of multiple myeloma according to the Durie and Salmon classification and its correlations with other disease characteristics. METHODS: Sixty-five immunohistochemical CD34-stained, paraffin-embedded bone marrow biopsies of multiple myeloma patients and 12 controls were studied. The mean number of microvessels per area in each sample was determined as the microvessel density (MVD). In addition, plasma cell infiltration of the bone marrow, serum beta2-microglobulin, immunoglobulin levels, C-reactive protein, and serum calcium concentration were measured in 22 patients with stage I multiple myeloma and in 43 patients in stage II-III. RESULTS: In myeloma patients, the bone marrow MVD was significantly higher than in controls (P<0.001). In 43 patients with stage II-III multiple myeloma, MVD was significantly higher than in 22 patients with stage I (median MVD 46 and 21 vessels/mm(2), respectively, P=0.005). Additionally, in stage II-III the bone marrow MVD correlated positively with the bone marrow plasma cell infiltration (r=0.55, P<0.001) and the serum beta2-microglobulin level (r=0.53, P<0.001), while in stage I patients no correlation could be found. CONCLUSIONS: Angiogenesis is significantly increased in stage II-III myeloma in comparison to stage I. In stages II-III, bone marrow angiogenesis is correlated with plasma cell infiltration and serum beta2-microglobulin levels.

Lack of HER-2/neu overexpression in non-Hodgkin's lymphoma.

OBJECTIVES: The HER-2/neu oncogene is overexpressed in many types of cancer and especially in 25% to 30% of breast cancers. Single reports mention HER-2/neu positivity in hematological malignancies like Hodgkins's disease and even diffuse large-cell lymphoma. OBJECTIVE: To test for HER-2/neu overexpression in patients with non-Hodgkin's lymphoma and the possible role of the recombinant monoclonal anti-HER-2/neu antibody trastuzumab (Herceptin) in the treatment of non-Hodgkin's lymphoma. MATERIALS AND METHODS: Serum samples from 87 consecutive unselected patients with non-Hodgkin's lymphoma were retrospectively retrieved from a serum bank and tested for the shed antigen of HER-2/neu using the Oncogene Sciences ELISA assay (Cambridge, MA, USA). From those lymphoma patients, the paraffin-embedded lymph-node specimens of 25 cases with diffuse large-cell lymphoma were stained with the HER-2/neu DAKO HercepTest. RESULTS: In 87 lymphoma patients, the serum level of HER-2/neu ranged from 3.6 to 244.1 ng/ml (median 8.0 ng/ml). Only 2 patients showed a marginal or increased HER-2/neu level with 15 ng/ml (which is the upper limit of normal) and 244.1 ng/ml, respectively. No patient with diffuse large-cell lymphoma showed HER-2/neu overexpression by immunhistochemistry of the lymph node. The paraffin block of the one patient with a very high HER-2/neu serum level was also stained for HER-2/neu overexpression. In this patient, suffering from a high-grade T-cell non-Hodgkin's lymphoma, no staining could be found. CONCLUSION: HER-2/neu is not overexpressed in non-Hodgkin's lymphoma and especially not in diffuse large-cell lymphoma, using a standardized immunochemistry technique with complementary serum testing. Thus, specific anti-HER-2/neu-targeted therapy should play no role in the treatment of non-Hodgkin's lymphoma.

Expression of bFGF, VEGF and c-met and their correlation with microvessel density and progression in prostate carcinoma.

BACKGROUND: Previously, we found angiogenesis measured as microvessel density (MVD) to be associated with both pathological stage and clinical outcome after radical prostatectomy (RP). In addition, we have shown that Vascular Endothelial Growth Factor (VEGF) is one of the important inducers of angiogenesis in prostate cancer (PC). The aim of this study was to investigate the expression of additional angiogenic factors, namely basic Fibroblast Growth Factor (hFGF) and the c-met receptor of Hepatocyte Growth Factor/Scatter Factor (HGF/SF) in PC. MATERIALS AND METHODS: Ninety-eight paraffin-embedded RP specimens and 20 adjacent normal prostatic tissues were evaluated for factor VIII staining and microvessel counting. Expression of VEGF (n=55), bFGF (n=65) and c-met (n=66) was studied by immunohistochemistry. Results were correlated with pathological grade and stage, MVD and clinical outcome. RESULTS: While adjacent benign tissue in RP specimens generally showed low MVD, VEGF-, bFGF- and c-met-expression, this was different in PC. All angiogenesis inducers were associated with stage while c-met as well as VEGF expression were associated with grade. Tumor progression was associated with grade and MVD. There was a clear correlation between VEGF and c-met expression and MVD. CONCLUSION: VEGF and c-met expression increase with tumor stage and grade, while bFGF expression increases only with tumor stage. In addition to VEGF, c-met seems to be important and clinically relevant to the induction of angiogenesis in PC. Both VEGF and c-met appear to influence tumor progression, mainly through their effect on MVD.

FISH--a new noninvasive method for the diagnosis of urinary bladder carcinomas.

Urinary bladder carcinoma is one of the most frequent malignant tumour diseases. The frequency increases with advancing age. The knowledge increase about genetic changes in tumour cells opens the possibility of a new noninvasive diagnosis with the help of fluorescence in situ hybridization (FISH). Comparable data are obtained by application of different diagnostic methods (fluorescence in situ hybridization, urinary bladder cancer ELISA, urinary cytology, histopathology) at different times from 6 coincidentally selected patients (preoperation, biopsy material and postoperation). The FISH test proved to be a sensitive method and correlated with the histopathological data.

Prognostic accuracy of individual uropathologists in noninvasive urinary bladder carcinoma: a multicentre study comparing the 1973 and 2004 World Health Organisation classifications.

BACKGROUND: Grading of noninvasive papillary urinary bladder carcinoma (PUC) is routinely performed in clinical oncologic practice; however, reports regarding diagnostic and prognostic accuracy are contradictory. OBJECTIVE: To compare the 1973 and 2004 World Health Organisation (WHO) classifications in terms of interobserver variability and prognostic implications. DESIGN, SETTING, AND PARTICIPANTS: Two hundred PUC were retrospectively reviewed by four independent expert genitourinary pathologists blinded with respect to patient identity and clinical outcome. Tumour grading was assigned according to the 1973 and 2004 WHO classifications. Surveying a mean postsurgical follow-up of 71.8 mo (range: 18-163 mo), clinical outcome in terms of recurrence-free and progression-free survival was recorded for all patients. INTERVENTION: All of the patients underwent transurethral resection of the bladder. MEASUREMENTS: The generalised κ (kappa statistic) for interobserver variability was calculated, and Kaplan-Meier analysis as well as univariate regression analysis were performed to evaluate prognostic implications in terms of recurrence and progression rates. RESULTS AND LIMITATIONS: During the follow-up, a total of 84 (42%) patients experienced recurrence, whereas another 18 (9%) patients featured disease progression. Owing to the rare presence of papillary urothelial neoplasms of low malignant potential (PUNLMP) in our cohort (0-3.5%), the 2004 WHO classification approached a two-tier system (low and high grade), which showed less interobserver variability than the 1973 classification (κ: 0.30-0.52 vs 0-0.37, respectively). In comparing the power of both classifications to separate indolent from aggressive PUC, striking pathologist-dependent differences became apparent. CONCLUSIONS: Both WHO classifications for grading of PUC suffer from substantial interobserver variability, with the 2004 WHO classification showing less interobserver variability. Stark differences in the prognostic power of the individual grading approaches were also found. These significant differences in the individual interpretation of the WHO grading schemes for noninvasive PUC highlight the necessity of better-defined criteria for conventional tumour grading; otherwise, the subdivision into prognostically different groups by conventional histomorphology might remain of limited value.

Prognostic impact of lymphovascular invasion in radical prostatectomy specimens.

OBJECTIVE: To estimate the prognostic value of lymphovascular invasion (LVI) in patients with node-negative prostate cancer treated by radical prostatectomy (RP). PATIENTS AND METHODS: In all, 412 patients with prostatic adenocarcinoma who had RP and pN0 status were analysed for all established standard pathological factors and LVI. The influence of these pathological findings on biochemical failure was evaluated by multivariate analysis with the Cox model. The mean (range) follow-up was 52.5 (10-116) months. RESULTS: LVI was identified in 42 patients (10.2%) and significantly associated with a high preoperative prostate-specific antigen (PSA) level, a high PSA density, high percentage of positive biopsy cores, high Gleason score, and seminal vesicle invasion. Of the 42 patients with LVI, 33 (79%) had a Gleason score of > or = 7 and 27 (64%) had pathological stage pT3. The 5-year biochemical-free survival was 87.3% for patients with no LVI and 38.3% with LVI on the RP specimen (P < 0.001). By multivariate analysis, LVI and Gleason score were independent predictors of biochemical failure. CONCLUSION: These results show that in addition to the Gleason score, only LVI is strongly correlated with biochemical failure after RP. These findings support the routine evaluation of LVI status in RP specimens and provide the option for its incorporation into nomograms predictive of oncological outcome.

Comparison of the ovine and porcine animal models for biocompatibility testing of vascular prostheses.

OBJECTIVE: Evaluation of the pig and sheep models for biocompatibility investigations of vascular prostheses (VP). DESIGN: Comparative analysis of animal experimental investigations involving two different animal models. MATERIALS AND METHODS: Commercially available polyester vascular prostheses (PET-VP) were implanted into two different animal models (infrarenal porcine aorta and ovine carotid artery). The costs, surgical handling, patency rate, and healing on the basis of macroscopic, microscopic, and immunohistochemical criteria were analyzed over a period of 3 months. RESULTS: Handling and operating times (63 +/- 10 versus 76 +/- 16 min; P = 0.125) did not differ significantly. The cost of the two animal models was comparable. Integration of the VP was complete in the sheep model, but varied in the pig model (two complete, four incomplete). Complete endothelialization of all VPs was observed in the pig, which contrasted with the sheep with complete (circular) endothelialization only in the region of the anastomosis. The thickness of neointima in the region of the anastomosis differed insignificantly; immunohistochemically, only periprosthetic Ki67 was significantly reduced (28.7 +/- 9.9 versus 6 +/- 0.9%; P = 0.002) in the sheep. CONCLUSIONS: In the porcine model, extremely good endothelialization of the VP was observed, with formation of a rapid neointimal hyperplasia. The ovine model was characterized by the fact that postoperative follow-up investigations were easy to perform. Complete endothelialization was not observed.

Perivascular epithelioid cell tumor (PEComa) with perirenal manifestation.

We present the first case report documenting an 8-month post-surgical follow-up of an exceedingly rare perivascular epithelioid cell tumor (PEComa) with a perirenal location. Furthermore, prognostic parameters discussed in the literature are summarized and concise information regarding imaging characteristics on magnetic resonance imaging is provided. In conclusion, our report points toward PEComa as a family of very rare mesenchymal neoplasms that should be included into deliberations concerning the differential diagnosis of perirenal mass lesions.

Analysis of immunoglobulin light chain rearrangements in the salivary gland and blood of a patient with Sjögren's syndrome.

Patients with Sjögren's syndrome (SS) have characteristic lymphocytic infiltrates of the salivary glands. To determine whether the B cells accumulating in the salivary glands of SS patients represent a distinct population and to delineate their potential immunopathologic impact, individual B cells obtained from the parotid gland and from the peripheral blood were analyzed for immunoglobulin light chain gene rearrangements by PCR amplification of genomic DNA. The productive immunoglobulin light chain repertoire in the parotid gland of the SS patient was found to be restricted, showing a preferential usage of particular variable lambda chain genes (V lambda 2E) and variable kappa chain genes (V kappa A27). Moreover, clonally related V(L) chain rearrangements were identified; namely, V kappa A27-J kappa 5 and V kappa A19-J kappa 2 in the parotid gland, and V lambda 1C-J lambda 3 in the parotid gland and the peripheral blood. V kappa and V lambda rearrangements from the parotid gland exhibited a significantly elevated mutational frequency compared with those from the peripheral blood (P < 0.001). Mutational analysis revealed a pattern of somatic hypermutation similar to that found in normal donors, and a comparable impact of selection of mutated rearrangements in both the peripheral blood and the parotid gland. These data indicate that there is biased usage of V(L) chain genes caused by selection and clonal expansion of B cells expressing particular V(L) genes. In addition, the data document an accumulation of B cells bearing mutated V(L) gene rearrangements within the parotid gland of the SS patient. These results suggest a role of antigen-activated and selected B cells in the local autoimmune process in SS.