Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer.Prostatic Neoplasms: Tumors or cancer of the PROSTATE.Prostate: A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.Cervical Intraepithelial Neoplasia: A malignancy arising in uterine cervical epithelium and confined thereto, representing a continuum of histological changes ranging from well-differentiated CIN 1 (formerly, mild dysplasia) to severe dysplasia/carcinoma in situ, CIN 3. The lesion arises at the squamocolumnar cell junction at the transformation zone of the endocervical canal, with a variable tendency to develop invasive epidermoid carcinoma, a tendency that is enhanced by concomitant human papillomaviral infection. (Segen, Dictionary of Modern Medicine, 1992)Prostatic Hyperplasia: Increase in constituent cells in the PROSTATE, leading to enlargement of the organ (hypertrophy) and adverse impact on the lower urinary tract function. This can be caused by increased rate of cell proliferation, reduced rate of cell death, or both.Carcinoma in Situ: A lesion with cytological characteristics associated with invasive carcinoma but the tumor cells are confined to the epithelium of origin, without invasion of the basement membrane.Uterine Cervical Neoplasms: Tumors or cancer of the UTERINE CERVIX.Adenocarcinoma: A malignant epithelial tumor with a glandular organization.Precancerous Conditions: Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)Racemases and Epimerases: Enzymes that catalyze inversion of the configuration around an asymmetric carbon in a substrate having one (racemase) or more (epimerase) center(s) of asymmetry. (Dorland, 28th ed) EC 5.1.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (TRANSURETHRAL RESECTION OF PROSTATE).Papillomavirus Infections: Neoplasms of the skin and mucous membranes caused by papillomaviruses. They are usually benign but some have a high risk for malignant progression.Vulvar Neoplasms: Tumors or cancer of the VULVA.Colposcopy: The examination, therapy or surgery of the cervix and vagina by means of a specially designed endoscope introduced vaginally.Papillomaviridae: A family of small, non-enveloped DNA viruses infecting birds and most mammals, especially humans. They are grouped into multiple genera, but the viruses are highly host-species specific and tissue-restricted. They are commonly divided into hundreds of papillomavirus "types", each with specific gene function and gene control regions, despite sequence homology. Human papillomaviruses are found in the genera ALPHAPAPILLOMAVIRUS; BETAPAPILLOMAVIRUS; GAMMAPAPILLOMAVIRUS; and MUPAPILLOMAVIRUS.Prostate-Specific Antigen: A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.Neoplasm Grading: Methods which attempt to express in replicable terms the level of CELL DIFFERENTIATION in neoplasms as increasing ANAPLASIA correlates with the aggressiveness of the neoplasm.Prostatitis: Infiltration of inflammatory cells into the parenchyma of PROSTATE. The subtypes are classified by their varied laboratory analysis, clinical presentation and response to treatment.Biopsy, Needle: Removal and examination of tissue obtained through a transdermal needle inserted into the specific region, organ, or tissue being analyzed.Vaginal Smears: Collection of pooled secretions of the posterior vaginal fornix for cytologic examination.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.PTEN Phosphohydrolase: A lipid phosphatase that acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.Cervix Uteri: The neck portion of the UTERUS between the lower isthmus and the VAGINA forming the cervical canal.Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.Prostatic Diseases: Pathological processes involving the PROSTATE or its component tissues.Vaginal Neoplasms: Tumors or cancer of the VAGINA.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Glutathione S-Transferase pi: A glutathione transferase that catalyzes the conjugation of electrophilic substrates to GLUTATHIONE. This enzyme has been shown to provide cellular protection against redox-mediated damage by FREE RADICALS.Tumor Virus Infections: Infections produced by oncogenic viruses. The infections caused by DNA viruses are less numerous but more diverse than those caused by the RNA oncogenic viruses.Uterine Cervical Dysplasia: Abnormal development of immature squamous EPITHELIAL CELLS of the UTERINE CERVIX, a term used to describe premalignant cytological changes in the cervical EPITHELIUM. These atypical cells do not penetrate the epithelial BASEMENT MEMBRANE.Anus Neoplasms: Tumors or cancer of the ANAL CANAL.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Electrosurgery: Division of tissues by a high-frequency current applied locally with a metal instrument or needle. (Stedman, 25th ed)Receptors, Androgen: Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Epithelium: One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Papanicolaou Test: Cytological preparation of cells collected from a mucosal surface and stained with Papanicolaou stain.Tissue Array Analysis: The simultaneous analysis of multiple samples of TISSUES or CELLS from BIOPSY or in vitro culture that have been arranged in an array format on slides or microchips.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Human papillomavirus 16: A type of ALPHAPAPILLOMAVIRUS especially associated with malignant tumors of the CERVIX and the RESPIRATORY MUCOSA.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Conization: The excision of a cone of tissue, especially of the CERVIX UTERI.Keratins: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Human papillomavirus 18: A type of human papillomavirus especially associated with malignant tumors of the genital and RESPIRATORY MUCOSA.Neoplasm Staging: Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.Alphapapillomavirus: A genus of DNA viruses in the family PAPILLOMAVIRIDAE. They preferentially infect the anogenital and ORAL MUCOSA in humans and primates, causing both malignant and benign neoplasms. Cutaneous lesions are also seen.Carcinoma: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)Transgenes: Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Carcinoma, Pancreatic Ductal: Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS.Neoplasms, Squamous Cell: Neoplasms of the SQUAMOUS EPITHELIAL CELLS. The concept does not refer to neoplasms located in tissue composed of squamous elements.Condylomata Acuminata: Sexually transmitted form of anogenital warty growth caused by the human papillomaviruses.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Cell Line, Tumor: A cell line derived from cultured tumor cells.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Carcinoma, Squamous Cell: A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Mice, Inbred C57BLTranscription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Neoplasm Regression, Spontaneous: Disappearance of a neoplasm or neoplastic state without the intervention of therapy.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Atypical small acinar proliferation: In urologic pathology, atypical small acinar proliferation, abbreviated ASAP, is a collection of small prostatic glands, on prostate biopsy, whose significance is uncertain and cannot be determined to be benign or malignant.CabazitaxelProstate saturation biopsy: Prostate saturation biopsy typically entails 40-80 core samples taken from the prostate under general anesthesia.Centers for Medicare and Medicaid Services]: Summary of Fee Schedule Policies, 2009]Squamous intraepithelial lesion: A squamous intraepithelial lesion (SIL) is an abnormal growth of epithelial cells on the surface of the cervix, commonly called squamous cells. This condition can lead to cervical cancer, but can be diagnosed using a Pap smear or a colposcopy.Alpha-1 blocker: Alpha-1 blockers (also called alpha-adrenergic blocking agents) constitute a variety of drugs that block α1-adrenergic receptors in arteries, smooth muscles, and central nervous system tissues.Cervical screening: Cervical screening is the process of detecting abnormal changes in the cervix before they can develop into cervical cancer. If the abnormal tissue or cells can be removed, then the disease can be prevented from developing.Adenocarcinoma of the lung: Adenocarcinoma of the lung (pulmonary adenocarcinoma) is a common histological form of lung cancer that contains certain distinct malignant tissue architectural, cytological, or molecular features, including gland and/or duct formation and/or production of significant amounts of mucus.Epithelial dysplasia: Epithelial dysplasia, a term becoming increasingly referred to as intraepithelial neoplasia, is the sum of various disturbances of epithelial proliferation and differentiation as seen microscopically. Individual cellular features of dysplasia are called epithelial atypia.ProstatectomyVulvar intraepithelial neoplasia: (ILDS D07.120) |ColposcopyProstatitisBreast biopsyPap testTumor progression: Tumor progression is the third and last phase in tumor development. This phase is characterised by increased growth speed and invasiveness of the tumor cells.Brain biopsyVaginal intraepithelial neoplasiaCancer biomarkers: A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer.Anal dysplasia: Anal dysplasia is a pre-cancerous condition which occurs when the lining of the anal canal undergoes abnormal changes. It can be classified as low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL)Hyfrecator: A hyfrecator is a low-powered medical apparatus used in electrosurgery on conscious patients, usually in an office setting. It is used to destroy tissue directly, and to stop bleeding during minor surgery.Androgen receptor: The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding either of the androgenic hormones, testosterone, or dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.Immunoperoxidase: Immunoperoxidase is a type of immunostain used in molecular biology, medical research, and clinical diagnostics. In particular, immunoperoxidase reactions refer to a sub-class of immunohistochemical or immunocytochemical procedures in which the antibodies are visualized via a peroxidase-catalyzed reaction.Stratified squamous epithelium: A stratified squamous epithelium consists of squamous (flattened) epithelial cells arranged in layers upon a basal membrane. Only one layer is in contact with the basement membrane; the other layers adhere to one another to maintain structural integrity.Squamous epithelial cell: In anatomy, squamous epithelium (squama- + -ous) is that whose outermost (apical) layer consists of thin, flat cells called squamous epithelial cells. The epithelium may be composed of one layer of these cells, in which case it is referred to as simple squamous epithelium, or it may possess multiple layers, referred to then as stratified squamous epithelium.Testicular atrophy: Testicular atrophy is a medical condition in which the male reproductive organs (the testes, which in humans are located in the scrotum) diminish in size and may be accompanied by loss of function. This does not refer to temporary changes, such as those brought on by cold.Tissue microarray: 215px|thumb|right|A Tissue MicroArray BlockGross pathology: Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.Keratin 6A: Keratin 6A is one of the 27 different type II keratins expressed in humans. Keratin 6A was the first type II keratin sequence determined.ABCD rating: ABCD rating, also called the Jewett staging system or the Whitmore-Jewett staging system, is a staging system for prostate cancer that uses the letters A, B, C, and D.Anaplastic carcinoma: Anaplastic carcinoma is a general term for a malignant neoplasm arising from the uncontrolled proliferation of transformed cells of epithelial origin, or showing some epithelial characteristics, but that reveal no cytological or architectural features of associated with more differentiated tumors, such as the glandular formation or special cellular junctions that typical of adenocarcinoma and squamous cell carcinoma, respectively.Ductal carcinoma: Ductal carcinoma is a type of tumor that primarily presents in the ducts of a gland.Bacterial glutathione transferase: Bacterial glutathione transferases (GSTs; EC 2.5.Squamous-cell carcinomaPituitary-specific positive transcription factor 1: POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1), also known as POU1F1, is a transcription factor for growth hormone.Mature messenger RNA: Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription known as precursor messenger RNA, it consists exclusively of exons, with all introns removed.Iroquois homeobox factor: Iroquois homeobox factors are a family of homeodomain transcription factors that play a role in many developmental processes.Jim Sinclair (activist): Jim Sinclair is an autism rights activist who, together with fellow autistics Kathy Lissner Grant and Donna Williams, formed Autism Network International (ANI) in 1992. Being the only one of the three with an internet connection, Sinclair became the original coordinator of ANI.MinC: The MinC protein is one of three proteins encoded by the minB operon and which is required to generate pole to pole oscillations prior to bacterial cell division as a means of specifying the midzone of the cell. This function is achieved by preventing the formation of the divisome Z-ring around the poles.Gene signature: A gene signature is a group of genes in a cell whose combined expression patternItadani H, Mizuarai S, Kotani H. Can systems biology understand pathway activation?
(1/308) Malignant transformation of human prostatic epithelium is associated with the loss of androgen receptor immunoreactivity in the surrounding stroma.
The cellular pathways involved in the pathogenesis of hormone resistance remain unclear. Studies evaluating the role of changes in human androgen receptor (hAR) expression in the progression of prostatic tumors have been inconclusive. Androgenic influence over prostatic growth is mediated via the regulation of interactions between stromal and epithelial cells. We hypothesized that neoplastic transformation of the prostate would be associated with alterations in hAR expression in the adjacent stroma. Using immunohistochemical techniques, we determined hAR positivity in the epithelium and adjacent stroma of sections from 17 benign and 39 malignant prostatic glands. We found that whereas the expression of the receptor decreased in both cellular compartments as the tissues dedifferentiated, the depletion was more pronounced in the stromal nuclei (P<0.0001). However, in sections from both untreated and hormone-resistant prostate cancer tissues, although heterogeneity of hAR expression in malignant epithelia was increased, there appeared to be a unique field effect around the cancerous prostate glands that resulted in a decreased expression of the receptor in the adjacent benign glands and its total loss in the surrounding stroma. The loss of hAR in the stroma adjacent to malignant prostatic epithelium may play an important role in prostate cancer progression. Furthermore, the similarity of the lack of stromal hAR expression in newly diagnosed and hormone-resistant prostate cancer (P = 0.85) may be an indication that the mechanisms responsible for the acquisition of hormone independence are established early in the malignant transformation process. (+info)
(2/308) De novo expression of CD44 in prostate carcinoma is correlated with systemic dissemination of prostate cancer.
AIMS: To evaluate the role of CD44 in early steps in the development of prostate cancer, and to assess the biological significance of preneoplastic lesions in prostate cancer. METHODS: 38 patients with clinically localised prostate cancer were studied. The standard form of CD44 (CD44H) and v6 isoform expressions were semiquantitatively evaluated on paraffin embedded tumour tissue by immunohistochemistry. Disseminated prostatic cells were detected by prostate specific membrane antigen reverse transcriptase polymerase chain reaction in the blood of each patient before radical prostatectomy. RESULTS: In normal or benign prostate glands, only basal cells showed CD44H and v6 labelling. Fourteen of the 38 prostate cancers (37%) had CD44H membranous staining of prostatic tumour cells. In 18 patients (47%), circulating prostatic cells were detected in blood before surgery. Although no correlation between the expression of CD44 and the Gleason score or staging was observed, a significant correlation was found between the expression of CD44H by tumour cells and prostatic cell blood dissemination (p = 0.04). In 28 cases, foci of prostatic intraepithelial neoplasia were observed, and nine had CD44H immunostaining. CONCLUSIONS: De novo expression of CD44 by prostatic tumour cells is associated with systemic dissemination of prostate cells independently of pathological criteria. (+info)
(3/308) Does screening for prostate cancer identify clinically important disease?
In this study the combination of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) is shown to be effective for detecting early prostate cancer in a urological out-patient setting. PSA provides the means to detect cancer in men with normal DRE that may otherwise present as so-called incidental cancer at transurethral resection of the prostate (TURP) for apparently benign disease or later in the course of its natural history as locally advanced or metastatic disease. PSA progression in men with incidental cancer has been previously demonstrated to be predicted more reliably by residual cancer on needle biopsy after TURP than by tumour in the resected specimen and, therefore re-staging such patients is worthwhile when further treatment would be considered. Among men selected for radical prostatectomy, non-palpable tumours detected with PSA more predictable in pathological extent than incidental cancer and their particular pathological characteristics suggest they include clinically significant tumours that would progress if untreated to palpable and eventually metastatic disease. In view of this progressive behaviour, cancer detected by PSA should be considered clinically significant particularly in men with a life expectancy of at least 10 years. Therefore screening should be offered for such individuals, to detect and treat tumours at a curable stage and thereby eliminate the high mortality and often protracted morbidity commonly associated with metastatic disease. (+info)
(4/308) Membrane type 1-matrix metalloproteinase (MT1-MMP) and MMP-2 immunolocalization in human prostate: change in cellular localization associated with high-grade prostatic intraepithelial neoplasia.
Membrane type 1-matrix metalloproteinase (MT1-MMP) is a known activator of latent MMP-2 (pro-MMP-2), and increased MMP-2 expression has been associated with tumor aggressiveness in prostate cancer. However, expression of MT1-MMP in human prostate tissue has not been described. We investigated the expression and immunolocalization of MT1-MMP and MMP-2 in the epithelial components of benign prostate epithelium, high-grade prostatic intraepithelial neoplasia (HGPIN), and prostate cancer. Tissue sections from the peripheral zone of 50 prostates (radical prostatectomy specimens) were chosen based on their containing benign glands, HGPIN, and prostate cancer glands. All 50 sections were immunostained for MT1-MMP and MMP-2 and were evaluated for staining pattern, uniformity, and intensity. Western blotting and gelatin zymography were done to confirm expression of MT1-MMP and activity of MMP-2, respectively. Comparisons were made between benign epithelium, HGPIN, and cancer. In benign glands, basal cells (BCs) uniformly stained intensely for MT1-MMP, whereas secretory cells (SCs) were rarely positive (P < 0.0001). Conversely in HGPIN, SCs showed consistent cytoplasmic staining (P < 0.0001). In cancer cells, staining was heterogeneous and varied from no staining to very intense staining in select glands. MMP-2 in normal tissue stained both BCs and the apical region of SCs, whereas in HGPIN, staining was observed in the SC in a predominantly cytoplasmic pattern. Similar to MT1-MMP, staining in cancer tissue for MMP-2 was heterogeneous; however, there was a significant association between the pattern of MMP-2 and MT1-MMP staining within the epithelial components of the cancer glands in individual specimens (P < 0.001). Finally, MMP-2 and MT1-MMP were confirmed to be expressed in the prostate tissues by gelatin zymography and Western blotting. In conclusion, we found that consistent changes in localization and intracellular distribution of MMP-2 and MT1-MMP were associated with the transition from benign prostate epithelium to HGPIN, suggesting that regulation of these enzymes is altered during the earliest stages of prostate cancer. (+info)
(5/308) Expression of pi-class glutathione S-transferase: two populations of high grade prostatic intraepithelial neoplasia with different relations to carcinoma.
BACKGROUND/AIMS: Patients with high grade prostatic intraepithelial neoplasia of the transition zone appear to be at increased risk of developing prostatic carcinoma, although not to the same degree as patients with high grade prostatic intraepithelial neoplasia of the peripheral/central zone. Previous investigations have shown loss of expression of pi-class glutathione S-transferase (GST-pi; an enzyme that protects against electrophilic carcinogens) in prostatic carcinoma and in high grade prostatic intraepithelial neoplasia. The aim of this study was to compare the expression of GST-pi in high grade prostatic intraepithelial neoplasia of the transition zone with that in high grade prostatic intraepithelial neoplasia of the peripheral/central zone (that is, non-transition zone). METHODS: Immunostaining with the anti-GST-pi antibody was performed on 20 high grade prostatic intraepithelial neoplasia samples of the transition zone, either isolated or associated with prostatic carcinoma (groups 1 and 2, respectively; 10 cases each) and on 20 high grade prostatic intraepithelial neoplasia samples of the non-transition zone, either isolated or associated with prostatic carcinoma (groups 3 and 4, respectively; 10 cases each). This study also included six samples of high grade prostatic intraepithelial neoplasia simultaneously present in the transition and non-transition zones and not associated with prostatic carcinoma (group 5). The presence of immunostaining, staining intensity, and the distribution of immunostaining were evaluated in the high grade prostatic intraepithelial neoplasia lesions and in the normal tissue and cancer areas. RESULTS: The GST-pi antibody stained the cytoplasm of the cells lining the ducts and acini of normal prostate tissue. Staining was stronger and more diffuse in the basal cell layer than in the luminal (or secretory) cell layer. Immunohistochemical staining with anti-GST-pi antibodies failed to detect the enzyme in all prostatic carcinoma foci but one. Two patterns were detected in high grade prostatic intraepithelial neoplasia. One was represented by GST-pi staining similar to that of the normal tissue (pattern A). The other deviated from it and was characterised by absence of GST-pi expression in the secretory cells and abundant expression in scattered basal cells (pattern B). Pattern A staining was seen more frequently in the transition than in the non-transition zone. Pattern B staining was seen mainly in high grade prostatic intraepithelial neoplasia of non-transition zone associated with cancer. CONCLUSIONS: The differential expression of GST-pi in the transition and non-transition zones indicates the existence of two populations with the morphological appearance of high grade prostatic intraepithelial neoplasia that might have different associations with carcinoma. (+info)
(6/308) Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.
Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized. (+info)
(7/308) Efficacious chemoprevention of primary prostate cancer by flutamide in an autochthonous transgenic model.
Although the etiology of prostate cancer is still not clear, family history, hormones, and age are thought to play a role in its initiation and progression. There is no cure for the advanced disease. Because prostate cancer initially develops as an androgen-dependent tumor, agents with antiandrogen activity have become the focus for chemoprevention of this disease. A pilot study was undertaken to test the efficacy of flutamide (an antiandrogen) in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer. Three groups of mice received s.c. implantation of slow-release flutamide pellets: (a) low-dose flutamide group (6.6 mg/kg); (b) high-dose flutamide group (33 mg/kg); and (c) control placebo group. Efficacy was measured by the absence of palpable tumor formation. Prostate tissues/tumors were harvested for evaluation by molecular and histology techniques. The low-dose flutamide group did not differ significantly from the placebo group, in which palpable tumors initially presented at 17 weeks of age, and by 33 weeks, all of the animals developed palpable tumors. In the high-dose flutamide group, however, tumors did not appear until 24 weeks, a lag of 7 weeks, and by 34 weeks, 42% of the animals were still tumor free. The period of time at which 50% of the animals had tumors was 33 weeks in the high-dose flutamide group, 24.5 weeks in the low-dose flutamide group, and 24.5 weeks in the placebo group. The difference between the placebo and high-dose flutamide groups was statistically significant (log rank, P = 0.0036; Wilcoxon's statistical analysis, P = 0.0060). Tumors from high-dose flutamide-treated animals were more differentiated and retained much of the normal glandular architecture compared with those of the placebo group, whose tumors consisted of sheets of poorly differentiated cells. The expression of T antigen in the prostate tissues of flutamide-treated animals (at 10 weeks age) was lower than that in the comparable placebo-treated group. Flutamide had the ability to suppress T antigen-driven carcinogenesis, resulting in a significant decrease in the incidence of prostate cancer and an increase in the latency period of prostate cancer in TRAMP mice. (+info)
(8/308) Increased expression of fibroblast growth factor 6 in human prostatic intraepithelial neoplasia and prostate cancer.
Fibroblast growth factors (FGFs) are known to play an important role in the growth of normal prostatic epithelial cells. In addition to their effects on proliferation, FGFs can promote cell motility, increase tumor angiogenesis, and inhibit apoptosis, all of which play an important role in tumor progression. To determine whether FGFs are overexpressed in human prostate cancers, we analyzed 26 prostate cancer RNAs by reverse transcription-PCR for expression of FGF3, FGF4, and FGF6, which cannot be detected in normal prostate tissue by this technique. Fourteen of 26 prostate cancers expressed FGF6 mRNA. No expression of FGF3 or FGF4 was detected. An ELISA of tissue extracts of normal prostate, high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer for FGF6 showed that this growth factor was undetectable in normal prostate but was present at elevated levels in 4 of 9 PIN lesions and in 15 of 24 prostate cancers. Immunohistochemical analysis with anti-FGF6 antibody revealed weak staining of prostatic basal cells in normal prostate that was markedly elevated in PIN. In the prostate cancers, the majority of cases revealed expression of FGF6 by the prostate cancer cells themselves. In two cases, expression was present in prostatic stromal cells. Exogenous FGF6 was able to stimulate proliferation of primary prostatic epithelial and stromal cells, immortalized prostatic epithelial cells, and prostate cancer cell lines in tissue culture. FGF receptor 4, which is the most potent FGF receptor for FGF6, is expressed in the human prostate in vivo and in all of the cultured cell lines. Thus, FGF6 is increased in PIN and prostate cancer and can promote the proliferation of the transformed prostatic epithelial cells via paracrine and autocrine mechanisms. (+info)