New insights about Haplosporidium pinnae and the pen shell Pinna nobilis mass mortality events.

Since early autumn 2016, Mass Mortality Events (MME) have drastically impacted the population of the fan mussel Pinna nobilis in the Mediterranean Sea. Haplosporidium pinnae, a newly described Haplosporidian species, has been considered the causative agent of the mortality outbreaks in association to opportunistic bacterial pathogens. In the present study, we first reported a cytological description of H. pinnae in moribund specimens of P. nobilis which were collected in the Gulf of Taranto (Ionian Sea, Italy) during summer 2018. Different life-cycle stages of the parasite, including uni- and binucleate cells, small plasmodia, big multinucleate plasmodia and sporocysts with spores, were detected in all the examined animals and most of the parasite cells were present in gills, mantle and digestive gland, while the spores were found only in the latter organ. Histology and molecular biology were also performed, confirming the nature of the infectious agent, as already reported in the area. Additionally, molecular study revealed the presence of bacteria from the Mycobacterium ulcerans - M. marinum complex but no evident macroscopical or microscopical lesions, just as no bacteria referred to Mycobacterium were observed by histology. In conclusion, the present study aimed to provide further contributions to the understanding of the mortality of P. nobilis, pointing to the role of the cytological method of investigation both for diagnostic and epidemiological purposes, and discussing the current epidemic situation in the Adriatic sea.

New insights in the expression of stromal caveolin 1 in breast cancer spread to axillary lymph nodes.

Recent evidence suggests that a loss of expression of caveolin in the stromal compartment (sCav-1) of human invasive breast carcinoma (IBC) may be a predictor of disease recurrence, metastasis and poor outcome. At present, there is little knowledge regarding the expression of sCav-1 at the metastatic sites. We therefore studied sCav-1 expression in IBCs and in their axillary lymph nodes to seek a correlation with cancer metastasis. 189 consecutive invasive IBCs (53 with axillary lymph node metastases and 136 without) were studied by immunohistochemistry, using a rabbit polyclonal anti-Cav-1 antibody. In IBCs sCav-1 was evaluated in fibroblasts scattered in the tumor stroma whereas in lymph nodes sCav-1 was assessed in fibroblast-like stromal cells. For the first time, we observed a statistically significant progressive loss of sCav-1 from normal/reactive axillary lymph nodes of tumors limited to the breast to metastatic axillary lymph nodes, through normal/reactive axillary lymph nodes of tumors with axillary metastatic spread. These data indicate that Cav-1 expressed by the stromal compartment of lymph nodes, somehow, may possibly contribute to metastatic spread in IBC.

Bioactive fatty acids in seafood from Ionian Sea and relation to dietary recommendations.

The objective of the present study was to determine lipid content, fatty acid composition and the recommended daily portion of 13 fish species, nine bivalves, six crustacean, three echinoderm and three cephalopod species, from the Mediterranean Sea (Southern Italy). Fatty acids profile varied significantly among species (p < .05); polyunsaturated fatty acids represented an important proportion, with docosahexaenoic and eicosapentaenoic acids in the highest amount. A high n3/n6 ratio was found in all species (from 1.0 in body wall of Holothuria polii and H. tubulosa to 10.9 in Mytilus galloprovincialis). The lipid nutritional quality indices (atherogenic index, thrombogenicity index and hypocholesterolaemic/hypercholesterolaemic fatty acid ratio) showed crustaceans Parapaeneus longirostris, Plesionika martia, Melicertus kerathurus, Nephrops norvegicus, as likely to be more beneficial for the consumer health. This paper will be of practical value from a health perspective for populations who consume seafood and a powerful marketing tool for farmers.

Seasonal changes of commercial traits, proximate and fatty acid compositions of the scallop Flexopecten glaber from the Mediterranean Sea (Southern Italy).

This study provides information on biological (gonadosomatic index), commercial quality (condition index and meat yield) and biochemical aspects (proximate composition, fatty acids) of the soft tissues of Flexopecten glaber reared in suspended cages in the Ionian Sea. The results showed that condition index (CI) and meat yield (MY) peaked in December (60 and 30%, respectively) and in April, May and June (from 53 to 60% for CI and from 34 to 36% for MY). Gonadosomatic index showed three main peaks in winter, spring and summer months. Contents of protein 8.18-11.9 g/100 g), lipid (0,.78-1.18 g/100 g) and carbohydrate (1.19-3.30 g/100 g) varied significantly during the study period. Saturated fatty acids was the dominant group, except in December when polyunsaturated fatty acids showed the highest proportion (43% of total FAs). Fatty acids of the n3 group were dominant with docosahexaenoic and eicosapentaenoic acids. Highest n3/n6 ratios were recorded in spring-summer specimens, with values > of 5. The results showed a better nutritional quality of scallops in May, July and December.

Doxycycline, an Inhibitor of Mitochondrial Biogenesis, Effectively Reduces Cancer Stem Cells (CSCs) in Early Breast Cancer Patients: A Clinical Pilot Study.

Background and objectives: Cancer stem cells (CSCs) have been implicated in tumor initiation, recurrence, metastatic spread and poor survival in multiple tumor types, breast cancers included. CSCs selectively overexpress key mitochondrial-related proteins and inhibition of mitochondrial function may represent a new potential approach for the eradication of CSCs. Because mitochondria evolved from bacteria, many classes of FDA-approved antibiotics, including doxycycline, actually target mitochondria. Our clinical pilot study aimed to determine whether short-term pre-operative treatment with oral doxycycline results in reduction of CSCs in early breast cancer patients. Methods: Doxycycline was administered orally for 14 days before surgery for a daily dose of 200 mg. Immuno-histochemical analysis of formalin-fixed paraffin-embedded (FFPE) samples from 15 patients, of which 9 were treated with doxycycline and 6 were controls (no treatment), was performed with known biomarkers of "stemness" (CD44, ALDH1), mitochondria (TOMM20), cell proliferation (Ki67, p27), apoptosis (cleaved caspase-3), and neo-angiogenesis (CD31). For each patient, the analysis was performed both on pre-operative specimens (core-biopsies) and surgical specimens. Changes from baseline to post-treatment were assessed with MedCalc 12 (unpaired t-test) and ANOVA. Results: Post-doxycycline tumor samples demonstrated a statistically significant decrease in the stemness marker CD44 (p-value < 0.005), when compared to pre-doxycycline tumor samples. More specifically, CD44 levels were reduced between 17.65 and 66.67%, in 8 out of 9 patients treated with doxycycline. In contrast, only one patient showed a rise in CD44, by 15%. Overall, this represents a positive response rate of nearly 90%. Similar results were also obtained with ALDH1, another marker of stemness. In contrast, markers of mitochondria, proliferation, apoptosis, and neo-angiogenesis, were all similar between the two groups. Conclusions: Quantitative decreases in CD44 and ALDH1 expression are consistent with pre-clinical experiments and suggest that doxycycline can selectively eradicate CSCs in breast cancer patients in vivo. Future studies (with larger numbers of patients) will be conducted to validate these promising pilot studies.

Human saliva as route of inter-human infection for mouse mammary tumor virus.

Etiology of human breast cancer is unknown, whereas the Mouse Mammary Tumor Virus (MMTV) is recognized as the etiologic agent of mouse mammary carcinoma. Moreover, this experimental model contributed substantially to our understanding of many biological aspects of the human disease. Several data strongly suggest a causative role of MMTV in humans, such as the presence of viral sequences in a high percentage of infiltrating breast carcinoma and in its preinvasive lesions, the production of viral particles in primary cultures of breast cancer, the ability of the virus to infect cells in culture. This paper demonstrates that MMTV is present in human saliva and salivary glands. MMTV presence was investigated by fluorescent PCR, RT-PCR, FISH, immunohistochemistry, and whole transcriptome analysis. Saliva was obtained from newborns, children, adults, and breast cancer patients. The saliva of newborns is MMTV-free, whereas MMTV is present in saliva of children (26.66%), healthy adults (10.60%), and breast cancer patients (57.14% as DNA and 33.9% as RNA). MMTV is also present in 8.10% of salivary glands. RNA-seq analysis performed on saliva of a breast cancer patient demonstrates a high expression of MMTV RNA in comparison to negative controls. The possibility of a contamination by murine DNA was excluded by murine mtDNA and IAP LTR PCR. These findings confirm the presence of MMTV in humans, strongly suggest saliva as route in inter-human infection, and support the hypothesis of a viral origin for human breast carcinoma.

Investigating molecular alterations to profile short- and long-term recurrence-free survival in patients with primary glioblastoma.

Glioblastoma (GB) is the most aggressive type of primary brain tumor. Despite the progress in recent years regarding the diagnosis and treatment of GB, the recurrence rate remains high, due to the infiltrative and dispersive nature of the tumor, which typically results in poor patient prognosis. In the present study, 19 formalin-fixed, paraffin-embedded GB samples were selected from patients with GB tumors. The samples were classified into a short or long recurrence-free survival (RFS) group, based on the time of first recurrence of the disease in the patients. The 19 samples were molecularly characterized for mutations in the isocitrate dehydrogenase 1 (IDH1) gene, amplification of the epidermal growth factor receptor (EGFR) gene, presence of the EGFR variant III, and methylation of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene. Then, the expression of 84 genes involved in cell-cell and cell-matrix interactions, and that of 84 microRNAs (miRNAs) associated with brain cancer, was profiled. In addition, a copy number variation analysis of 23 genes reported to undergo frequent genomic alterations in human glioma was also performed. Differences in the expression levels of a number of genes were detected across the short and long RFS groups. Among these genes, 5 in particular were selected, and a 5-genes combination approach was developed, which was able to differentiate between patients with short and long RFS outcome. The high levels of sensitivity and precision displayed by this 5-genes combination approach, which were confirmed with a cross-validation method, provide a strong foundation for further validation of the involvement of the aforementioned genes in GB in a larger patient population. In conclusion, the present study has demonstrated how the expression pattern of miRNAs and mRNAs in patients with GB defines a particular molecular hallmark that may increase or reduce the aggressive behavior of GB tumors, thus influencing the survival rates of patients with GB, their response to therapy and their tendency to suffer a relapse.

Lipolysis using a new 1540-nm diode laser: a retrospective analysis of 230 consecutive procedures.

BACKGROUND: Although traditional liposuction still remains the most required body sculpting procedure, laser lipolysis systems are becoming increasingly popular. The feasibility and efficacy of a new 1540-nm diode laser for suction-assisted laser lipolysis were evaluated. METHODS: Two hundred-thirty patients underwent a new 1540-nm diode laser lipolysis. Outcomes were determined by case notes, clinical review of side effects, and a questionnaire through which patient satisfaction was assessed. Macroscopic and histologic effects on subcutaneous fat and collagen deposition were evaluated. Moreover thermal effects were studied through thermography. RESULTS: The treated regions were abdomen in 56 cases, thighs in 54, trochanteric area in 27, flanks in 17, neck in 14, arms in 12, breast in 11, hips in 7, knees in 3; 29 cases were revisions of previous lipoplasties. No adverse effect as scarring, infection, burns, hypopigmentation, bruising, or swelling was observed. The required effects of laser lipolysis such as contour reshaping and skin tightening were achieved in almost all patients with high levels of satisfaction after treatment. CONCLUSION: Our investigation highlighted the safety and efficacy of the new 1540-nm diode laser assisted liposuction device for removal of small volumes of fat deposits associated with concurrent subdermal tissue contraction, tolerance and quick recovery time.

Hydrodynamism and its influence on the reproductive condition of the edible sea urchin Paracentrotus lividus.

Despite the large body of work published in the last two decades on the reproduction of the sea urchin Paracentrotus lividus, the reproductive aspects linked to hydrodynamic conditions and their influence on gonad production remain poorly understood. The present paper aims to evaluate the effect of hydrodynamism on the reproductive cycle of P. lividus. Variability in the gonadosomatic index (GSI) of P. lividus was estimated seasonally from 2007 to 2008 at two shallow sub-littoral flat basaltic areas at Ustica Island (Western Mediterranean). GSI was higher in the sites characterized by low hydrodynamism than in those with high hydrodynamism. Results also suggest a possible role for hydrodynamism in triggering processes of resource limitation (food shortage), probably by interfering with P. lividus feeding activity.

Metronomic ceramide analogs inhibit angiogenesis in pancreatic cancer through up-regulation of caveolin-1 and thrombospondin-1 and down-regulation of cyclin D1.

AIMS: To evaluate the antitumor and antiangiogenic activity of metronomic ceramide analogs and their relevant molecular mechanisms. METHODS: Human endothelial cells [human dermal microvascular endothelial cells and human umbilical vascular endothelial cell (HUVEC)] and pancreatic cancer cells (Capan-1 and MIA PaCa-2) were treated with the ceramide analogs (C2, AL6, C6, and C8), at low concentrations for 144 hours to evaluate any antiproliferative and proapoptotic effects and inhibition of migration and to measure the expression of caveolin-1 (CAV-1) and thrombospondin-1 (TSP-1) mRNAs by real-time reverse transcription-polymerase chain reaction. Assessment of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Akt phosphorylation and of CAV-1 and cyclin D1 protein expression was performed by ELISA. Maximum tolerated dose (MTD) gemcitabine was compared against metronomic doses of the ceramide analogs by evaluating the inhibition of MIA PaCa-2 subcutaneous tumor growth in nude mice. RESULTS: Metronomic ceramide analogs preferentially inhibited cell proliferation and enhanced apoptosis in endothelial cells. Low concentrations of AL6 and C2 caused a significant inhibition of HUVEC migration. ERK1/2 and Akt phosphorylation were significantly decreased after metronomic ceramide analog treatment. Such treatment caused the overexpression of CAV-1 and TSP-1 mRNAs and proteins in endothelial cells, whereas cyclin D1 protein levels were reduced. The antiangiogenic and antitumor impact in vivo of metronomic C2 and AL6 regimens was similar to that caused by MTD gemcitabine. CONCLUSIONS: Metronomic C2 and AL6 analogs have antitumor and antiangiogenic activity, determining the up-regulation of CAV-1 and TSP-1 and the suppression of cyclin D1.

A mouse mammary tumor virus env-like exogenous sequence is strictly related to progression of human sporadic breast carcinoma.

A viral etiology of human breast cancer (HBC) has been postulated for decades since the identification of mouse mammary tumor virus (MMTV). The detection of MMTV env-like exogenous sequences (MMTVels) in 30% to 40% of invasive HBCs increased attention to this hypothesis. Looking for MMTVels during cancer progression may contribute to a better understanding of their role in HBC. Herein, we analyzed HBC preinvasive lesions for the presence of MMTVels. Samples were obtained by laser microdissection of FFPE tissues: 20 usual-type ductal hyperplasias, 22 atypical ductal hyperplasias (ADHs), 49 ductal carcinomas in situ (DCISs), 20 infiltrating ductal carcinomas (IDCs), and 26 normal epithelial cells collateral to a DCIS or an IDC. Controls included reductive mammoplastic tissue, thyroid and colon carcinoma, and blood samples from healthy donors. MMTVels were detected by fluorescence-nested PCR. DNA samples from the tissues of nine patients were analyzed by real-time quantitative PCR, revealing a different viral load correlated with stage of progression. Furthermore, as never previously described, the presence of MMTVels was investigated by chromogenic in situ hybridization. MMTVels were found in 19% of normal epithelial cells collateral to a DCIS or an IDC, 27% of ADHs, 82% of DCISs, and 35% of IDCs. No MMTVels were found in the control samples. Quantitative PCR and chromogenic in situ hybridization confirmed these results. These data could contribute to our understanding of the role of MMTVels in HBC.

ALK-1-negative anaplastic large cell lymphoma associated with breast implants: a new clinical entity.

Concerns have been raised recently regarding the increasing number of reports of non-Hodgkin lymphoma (NHL) that developed in close proximity to silicone or saline breast implants. In particular, an increased risk of anaplastic large cell lymphoma (ALCL) in patients with breast prostheses has been proposed. We reviewed clinical and pathologic findings in 40 women who received a diagnosis of breast NHL arising in association with breast implants and of 27 patients who had a diagnosis of ALCL with breast involvement reported in the published literature. Among the 40 reported cases of prosthesis-associated breast lymphomas, 28 were anaplastic lymphoma kinase-1-negative (ALK-1(-)) ALCLs, whereas of 27 ALCLs in patients without implants found in the literature, only 10 were ALK-1(-). The finding of 28 cases of breast ALK-1(-) ALCL occurring in patients with implants compared with 10 cases in women without implants is in favor of an association between silicone breast prostheses and ALK-1(-) ALCL. Although the incidence of this type of lymphoma remains remarkably low given that breast prostheses have been widely used for decades, clinical and pathologic evidence for a causative role is becoming dramatically strong. The histologic, phenomenologic, and clinical similarities of the majority of implant-related ALK-1(-) ALCLs suggest a common mechanism, especially when compared with the counterpart of patients without implants in which very few and highly dishomogeneous cases of the same malignancy were detected. There is convincing evidence that primary implant-related ALK-1(-) ALCL represents a distinct clinicopathologic entity that has been inappropriately fitted into the category of systemic ALK-1(-) ALCL. Thus it should be recognized as a separate category and classified on its own.

Merkel cell carcinoma of the lower extremity: report of four cases and new considerations.

Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous malignancy that predominantly arises in the head and neck region. We describe clinical features, diagnosis, and treatment in 4 cases of MCC, presenting an uncommon female predominant occurrence and an unusual primary site: the lower limb. In all cases diagnosis was established by histopathologic examination. Primary MCC and locally recurrence disease were treated in all patients with a wide surgical excision (3-cm margin) including fascia. Lymphadenectomy was reserved for a patient with clinical evidence of nodal involvement. Both chemotherapy administered in 2 cases and radiotherapy in 1 case produced limited responses. Early diagnosis is critical because this tumor is aggressive and has a high rate of local recurrence and metastatic spread. However, its nondistinctive appearance frequently delays diagnosis and its rarity avoids an optimal treatment guideline setting.

Cardiac expression of adenine nucleotide translocase-1 in transgenic mice overexpressing bovine GH.

Heart hypertrophy is a common finding of acromegaly, a syndrome due to GH excess. Impairment of adenine nucleotide translocase-1 (ANT-1) gene, the main mitochondrial ADP/ATP exchanger, leads to cardiac hypertrophy. The aim of the study was to evaluate cardiac expression and the functional role of ANT-1 in 1- to 12-month-old transgenic mice overexpressing bovine GH (acromegalic mice, Acro) and littermate controls (wild-type mice, Wt). GH specificity of protein degree variation was assessed treating Acro with pegvisomant, a GH receptor competitor. Tissue levels of ANT-1, NF-kappaB, ATP, and lactic acid were evaluated by western blot, bioluminescence, and Fourier transform infrared spectroscopy respectively. The degree of ANT-1 expression was higher in 1-month-old Acro than in Wt (47+/-5% OD vs 33+/-4% OD, P<0 01). On the contrary, ANT-1 expression was lower in 3- to 12-month-old Acro than in Wt (P<0 03). Changes in ANT-1 expression were associated with consistent changes of cellular ATP content, increasing at 1 month (P<0 05) and reducing thereafter in Acro when compared with Wt (P<0 04). Treatment with pegvisomant abolished ANT-1 and ATP changes observed in 1- and 3-month-old Acro, thus supporting a GH-dependent mechanism. Reduced ATP generation in hypertrophied hearts of older Acro was associated with increased lactic acid levels suggesting that part of energy was due to glycolysis. Variations in ANT-1 expression were linked to GH through changes in NF-kappaB, the levels of which changed accordingly. In conclusion, 1-month-old acromegalic mice had increased ANT-1 expression and higher degree of ATP production. Long-standing disease was associated with a consistent reduction of ANT-1 and ATP tissue levels, which became GH-independent in older animals. This study demonstrated a direct effect of GH on key proteins involved in energy metabolism of acromegalic hearts.

Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma?

OBJECTIVE: HRPT2 gene mutations are associated with parathyroid carcinomas, and absence of parafibromin immunoreactivity has been suggested as a diagnostic marker of malignancy. The aim of our study was to extend parafibromin studies in a series of benign and malignant parathyroid tumors and cross-validate the results of immunohistochemistry with those of HRPT2 analysis. DESIGN AND PATIENTS: We performed parafibromin and cyclin D1 immunostaining and HRPT2 gene analysis using loss of heterozygosity studies and sequencing analysis in parathyroid specimens from 11 patients with carcinoma (eleven primary tumors, one skin, and four lung metastases), 22 with sporadic adenomas, and 4 with atypical adenomas. RESULTS: Ten out of eleven parathyroid cancers were negative for parafibromin staining and showed HRPT2 gene abnormalities. The remaining sample was negative for immunostaining and genetic analyses. All but one sporadic adenomas showed parafibromin immunoreactivity and no HRPT2 gene abnormalities. The sample with negative immunostaining carried an HRPT2 mutation. Two atypical adenomas were positive and two negative with parafibromin staining. No HRPT2 abnormalities were found in these samples. Cyclin D1 expression was heterogeneous and there was no relationship between expression/expression level of cyclin D1 and parafibromin expression. CONCLUSIONS: We have shown that negative parafibromin staining is almost invariably associated with HRPT2 mutations and confirm that loss of parafibromin staining strongly predicts parathyroid malignancy. In clinical practice, these tests could be particularly useful in the subset of parathyroid tumors with equivocal histological examination. However, their diagnostic value in this setting remains to be proven.

Markers of cell proliferation, apoptosis, and angiogenesis in thyroid adenomas: a comparative immunohistochemical and genetic investigation of functioning and nonfunctioning nodules.

OBJECTIVE: To perform (i) an immunohistochemical investigation of cell proliferation, apoptosis, angiogenesis, and malignancy markers in 15 functioning and 15 nonfunctioning thyroid adenomas, and in normal adjacent tissue, and (ii) a genetic analysis of thyroid-stimulating hormone receptor (TSH-r), Gsalpha, and RAS mutations in the same group of adenomas, in order to describe their expression within tissues and to correlate them with the hormonal functioning. DESIGN: Thirty patients who underwent surgery for a solitary thyroid nodule were included in the study. Adenomas and normal adjacent tissues were evaluated by immunohistochemistry using the following antibodies: MIB-1 for proliferative activity, bcl-2 and mutant p53 for apoptosis control, vascular endothelial growth factor-A (VEGF-A) for angiogenic activity, and galectin-3 as a marker for malignancy. To calculate microvascular density, "hot spots" were selected and defined by cells positive for CD34 staining. Genetic analysis for TSH-r, Gsalpha, and H-, K-, and N-RAS mutations was performed on adenoma specimens. MAIN OUTCOMES: Our results evidenced that a proportion of both functioning and nonfunctioning adenomas showed immunohistochemical phenotypes similar to normal adjacent tissue. No differences were found between functioning and nonfunctioning thyroid adenomas with regard to the expression of markers associated to angiogenesis (VEGF-A, microvascular density) and apoptosis control (mutant p53, bcl-2). All adenomas resulted negative for galectin-3 immunostaining. MIB-1 was the only marker showing a substantial difference of expression between the two groups of adenomas. TSH-r mutations were found in 12 out of 15 functioning adenomas, whereas the absence of Gsalpha and H-, K-, and N-RAS mutations was demonstrated in all adenomas. CONCLUSIONS: Our data suggest that the differences between functioning and nonfunctioning thyroid adenomas are restricted to the genetic mutations of the TSH-r, to the hormonal status of tumors, and to the proliferative activity, not involving markers of apoptosis control and angiogenesis.

Microvessel density in human normal and neoplastic parathyroids.

Objective. Information on angiogenesis in parathyroid pathology is scanty and in particular no data are available in parathyroid carcinomas. The aim of this study was to analyze angiogenesis as microvascular density (MVD) in parathyroid neoplastic progression from normal gland to adenoma and carcinoma. Methods. Sections from formalin-fixed, paraffin-embedded specimens of 33 normal parathyroids, 43 sporadic parathyroid adenomas, and 6 parathyroid carcinomas were cut for immunohistochemistry using anti-endothelial marker CD34. MVD was evaluated in each specimen as number microvessels per mm2. MVD data were compared with some anatomoclinical parameters as tumor size, serum calcium, and parathyroid hormone (PTH) level. Results. All normal parathyroid glands, all carcinomas, and 8 adenomas out of 43 (18%) showed MVD less than 100 microvessels/mm2 (median 70.8; 95%CI 66.9-88.5); in the majority of parathyroid adenomas (n = 35; 82%) the number of microvessels/mm2 was higher than 100 (median 188.3; 95%CI 174.9-210.1). In adenomas both preoperative serum intact PTH concentration and the diameters were significantly and inversely related to the microvessel density (r = 0.320, p < 0.05 and r = 0.334, p < 0.05, respectively). Conclusions. This study shows that in parathyroid adenomas MVD is heterogeneous and negatively related to the endocrine activity (secretory status and tumor size). Therefore, angiogenesis in parathyroid adenomas and carcinomas appears to be an early event, which does not follow a parallel increase in size.

Intratumoral microvessel density in advanced epithelial ovarian cancer and its use as a prognostic variable.

BACKGROUND: The aim of this retrospective study was to assess whether the intratumoral microvessel density (IMD) in primary tumour specimens had any impact on the clinical outcome of patients with advanced epithelial ovarian cancer treated in two Italian departments of gynaecological oncology. MATERIALS AND METHODS: The study was conducted on 101 patients who underwent initial surgery followed by platinum-based chemotherapy (37) or paclitaxel/platinum-based chemotherapy (64) for International Federation of Gynecology and Obstetrics (FIGO) stage III-IV epithelial ovarian cancer. The median follow-up of survivors from initial surgery was 65 months (range, 27 to 132 months). Paraffin-embedded sections of primary tumour specimens were analysed for IMD by immunohistochemistry using anti-CD34 antibodies. RESULTS: Progression-free survival and overall survival were significantly better in patients with IMD > or =40 microvessels/field compared with those with lower IMD (p = 0.0105 and p = 0.0065, respectively). Cox model showed that IMD was the strongest independent prognostic variable for both progression-free survival (p = 0.0267) and overall survival (p = 0.0189). CONCLUSION: An elevated IMD was associated with a significantly better progression-free survival and overall survival in patients with stage III-IV epithelial ovarian cancer who underwent initial surgery followed by chemotherapy, mainly consisting of a paclitaxel/platinum-based regimen.