Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer.

The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor beta (ERbeta). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production.

HPV prevalence among healthy Italian male sexual partners of women with cervical HPV infection.

Genital human papillomavirus (HPV) is the causative agent of cervical cancer and is the most common sexually transmitted infection. Only limited and controversial data are available regarding HPV transmission in male sexual partners of women with cervical intraepithelial neoplasia (CIN). The aim of this study was to investigate the prevalence and the genotype distribution of HPV in penile scrapings of a series of Italian men, who had no visible penile lesions and were partners of women who were affected, or had been affected previously by cervical intraepithelial neoplasia or who were infected with HPV.

Clinical role of p16INK4a expression in liquid-based cervical cytology: correlation with HPV testing and histologic diagnosis.

p16INK4a is overexpressed in high-risk human papillomavirus (HR-HPV)-infected preneoplastic and neoplastic lesions of the uterine cervix. Our aim was to verify whether p16 is a diagnostic marker also in cervical liquid-based cytology. We performed p16 immunocytochemical analysis and the Hybrid Capture 2 (HC2) test (Digene, Gaithersburg, MD) for HR-HPV infection in 471 ThinPrep-processed (Cytyc, Boxborough, MA) cervicovaginal samples and correlated the results with histologic findings.

Expression of Fas and Fas ligand in human testicular germ cell tumours.

In the present study, we analysed the expression of Fas ligand (FasL) and its cognate receptor Fas in 14 seminomatous testicular germ cell tumours (TGCT) and six normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for immunohistochemistry (IHC) experiments. Quantitative RT-PCR experiments demonstrated in TGCT a significant (p < 0.

Non-Hodgkin lymphomas concurrent with HHV8-associated Kaposi's sarcoma in the same lymph node in AIDS and non-AIDS patients.

Background: The association between lymphomas and Kaposi's sarcoma has been described since 1920. The simultaneous presence of the 2 pathologic entities within the same lymph node is a rare and interesting occurrence. In the few cases described, the presence of human herpesvirus 8 (HHV8) and Epstein-Barr virus (EBV) in the different neoplastic areas was investigated only by immunohistochemistry and in situ hybridization studies.

HLA-A, -B, -C expression in colon carcinoma mimics that of the normal colonic mucosa and is prognostically relevant.

Whether human leukocyte antigen (HLA)-A, -B, -C expression has any predictive value on the prognosis of human malignancies remains controversial. Herein, monoclonal antibodies with preferential reactivity for HLA-A, HLA-B, and HLA-C (HCA2, HC10, and L31) were used to stain an archival collection of 291 formalin-fixed/paraffin-embedded tissues, comprising neoplastic lesions from stages II and III colon carcinoma patients (n=165), and the uninvolved, morphologically normal mucosae from a subset (n=126) of these patients. Marked staining variability was detected not only in the tumors as in previous studies, but also in the normal paired mucosae.

Chromogenic in situ hybridization to detect HER-2/neu gene amplification in histological and ThinPrep-processed breast cancer fine-needle aspirates: a sensitive and practical method in the trastuzumab era.

The increasing evidence of trastuzumab efficacy in breast cancer (BC) patients means that an accurate and reproducible evaluation of HER-2 statusis of paramount importance in histological and in cytological samples. Currently, the two main methods used to analyze HER-2 amplification or overexpression are fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Although the two methods are strongly correlated for histological tissue, the evaluation of tumor morphology through FISH may be difficult and fluorescence fades quickly.

Immunohistochemical expression of p16(INK4a) is predictive of HR-HPV infection in cervical low-grade lesions.

The p16(INK4a) is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclin-dependent kinases involved in the phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7 oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16 pathway, leads to p16 upregulation. Although it is widely reported that p16 is overexpressed in a high percentage of preneoplastic lesions and in almost all carcinomas of the uterine cervix, protein upregulation and its correlation with HPV infection in low-grade lesions is still being debated.

Simultaneous determination of 16 anti-HIV drugs in human plasma by high-performance liquid chromatography.

Therapeutic drug monitoring (TDM) is pivotal to improve the management of HIV infection. Here, a HPLC-UV method has been developed to quantify simultaneously seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir; PIs), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine; NRTIs), and two non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine; NNRTIs) in human plasma. The volume of the plasma sample was 600 microL.

Fenretinide: a p53-independent way to kill cancer cells.

The synthetic retinoid fenretinide [N-(4 hydroxyphenyl)retinamide] induces apoptosis of cancer cells and acts synergistically with chemotherapeutic drugs, thus providing opportunities for novel approaches to cancer therapy. The upstream signaling events induced by fenretinide include an increase in intracellular levels of ceramide, which is subsequently metabolized to GD3. This ganglioside triggers the activation of 12-Lox (12-lipoxygenase) leading to oxidative stress and apoptosis via the induction of the transcription factor Gadd153 and the Bcl-2-family member protein Bak.

Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma.

Background: We explored the expression of Fatty Acid Synthase (FAS) in lung carcinomas and its association with clinico-pathological features and prognosis. FAS is a recently discovered molecule involved in the energy supply of normal cells. FAS is also overexpressed in neoplastic tissues because of their increased necessity for energy.

Phenotypic changes of p53, HER2, and FAS system in multiple normal tissues surrounding breast cancer.

To determine whether phenotypic field changes occur in tissues adjacent to carcinoma, we assayed, by immunohistochemistry, the expression of HER-2, p53, Fas, and FasL in 72 breast cancers (BC) and multiple autologous peritumoral tissues (PTTs) sampled up to 5 cm distance and in 44 benign breast tumors (BBTs). About 5% and 3% of the PTTs and 4.5% and 6.

Gangliosides link the acidic sphingomyelinase-mediated induction of ceramide to 12-lipoxygenase-dependent apoptosis of neuroblastoma in response to fenretinide.

Background: The lipid second messenger ceramide, which is generated by acidic and neutral sphingomyelinases or ceramide synthases, is a common intermediate of many apoptotic pathways. Metabolism of ceramide involves several enzymes, including glucosylceramide synthase and GD3 synthase, and results in the formation of gangliosides (GM3, GD3, and GT3), which in turn promote the generation of reactive oxygen species (ROS) and apoptosis. Fenretinide, a retinoic acid derivative, is thought to induce apoptosis via increases in ceramide levels, but the link between ceramide and subsequent apoptosis in neuroblastoma cells is unclear.

DNA demethylation is directly related to tumour progression: evidence in normal, pre-malignant and malignant cells from uterine cervix samples.

A computer-assisted assay based on the quantitative analysis of DNA methylation in individual interphase nuclei by indirect immunolabelling with anti-5-methylcytosine antibodies was recently developed in our laboratory. In situ analyses were performed on individual nuclei from normal and experimentally hypo- or hypermethylated cultured cells as well as on human peripheral blood B-lymphocytes from normal and chronic lymphoid leukemia (CLL) samples. We present the results obtained on cells from patients affected by different degrees of preneoplastic or neoplastic changes of the uterine cervix as compared to normal controls.

Role and prognostic significance of CD44s expression in colorectal cancer.

Unlabelled: The purpose of this study was to clarify the role and the predictive strength of the adhesion molecule CD44s (standard isoform) in colorectal carcinogenesis.

Materials And Methods: CD44s immunohistochemical expression was evaluated in 100 patients with colon adenoma and 100 patients with colon adenocarcinoma and adjacent non-neoplastic mucosa (ANNM). The patients were followed-up for five years.

Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent nonneoplastic mucosa.

The normal mucosa-adenoma-carcinoma sequence in colon pathology provides an attractive model of tumor progression. The role of tumor suppressor genes, oncogenes, and proliferative markers in tumorogenesis has evolved considerably in the last decade. By immunohistochemistry means, we have studied p53, bcl-2, c-myc, p21-ras, ki67, and fatty acid synthase (a fatty-acid-synthesizing enzyme) in normal, dysplastic, and neoplastic mucosa.

Urothelial toxicity following conditioning therapy in bone marrow transplantation and bladder cancer: morphologic and morphometric comparison by exfoliative urinary cytology.

Since cyclophosphamide and busulphan used for therapy of bone marrow transplantation (BMT) can cause urothelial cell changes similar to those found in bladder cancer, comparative morphologic and morphometric urinary cytologic research was carried out, examining 812 urine samples taken from 121 patients undergoing BMT and 60 urine samples from 20 patients with bladder cancer. The morphological results showed some differences in the characteristics of the urinary sediment in urothelial toxicity caused by conditioning therapy in BMT and in bladder cancer; among these were background, cellularity, leukocytes, urothelial cell arrangement, cell shape and size, vacuolization, mitosis, and nucleoli. A comparative morphometric study was also carried out, showing differences regarding cell area, nuclear area and perimeter, and N/C ratio, especially between well-differentiated bladder cancer and urothelial toxicity.

Use of monoclonal antibodies to human breast-tumor-associated antigens in the diagnosis of fine-needle aspirates of breast nodules: results of a multicenter study.

Fine-needle aspiration (FNA) cytology is being increasingly employed in conjunction with physical examination and mammography in the pre-surgical diagnosis of breast nodules. In the present study, we have submitted to multicenter validation an immunocytochemical test which employs monoclonal antibodies (MAbs) to breast-tumor-associated antigens (BTAA) for the diagnosis of breast cancer. The results of this analysis, which has evaluated 846 FNAs, show that the immunological test has a sensitivity of 88.

Combinations of monoclonal antibodies can distinguish primary lung tumors from metastatic lung tumors sampled by fine needle aspiration biopsy.

Transthoracic fine needle aspiration (FNA) biopsies performed under computed tomography (CT) scan (CT-FNA) have greatly improved the cytodiagnosis of lung tumors. However, the distinction between a primary lesion and a metastatic lesion still may be difficult on the basis of morphologic criteria. To evaluate whether a selected panel of monoclonal antibodies (MoAb) to tumor-associated antigens (TAA) can improve the diagnostic potential of FNA, we have immunocytochemically analyzed 122 pulmonary CT-FNA.

Use of selected combinations of monoclonal antibodies to tumor associated antigens in the diagnosis of neoplastic effusions of unknown origin.

While conventional cytodiagnosis can, in most instances, recognize cancer cells in metastatic effusions from solid tumors, the cellular type or the organ of origin of the primary neoplasia can rarely be determined only on the basis of their morphology. In the present study we have evaluated whether immunocytochemical techniques can be used to overcome this limitation by employing a panel of monoclonal antibodies (MoAbs) to tumor associated antigens (TAA) which lack detectable reactivity with mesothelial cells. To this end we have analyzed, by indirect immunofluorescence, cytospins of 60 malignant effusions of unknown origin.

Use of monoclonal antibodies to human breast-tumor-associated antigens in fine-needle aspirate cytology.

Fine-needle aspiration cytology (FNAC) is currently used in evaluating the nature of breast nodules. In the present study we have examined whether monoclonal antibodies (MAbs) to breast-tumor-associated antigens (BTAA) can be employed in FNAC for the diagnosis of breast cancer. For this purpose we have used 2 murine MAbs recognizing 2 distinct BTAA expressed by breast tumors, irrespective of their histotype, in an indirect avidin-biotin immunohistochemical technique on aspirate smears.