In vivo prostate cancer detection and grading using restriction spectrum imaging-MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI. METHODS: In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens. RESULTS: RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade. CONCLUSIONS: RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.

Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.

Nonepithelial tumors and tumor-like lesions of the prostate gland.

Many significant benign and malignant nonepithelial tumors and stromal tumor-like lesions arise in the prostate gland. Although such lesions are rare, their recognition by the pathologist is essential because their treatment and prognosis are quite variable. In this review, lesions of the specialized prostatic stroma, that is, lesions that can be seen in the stroma of the prostate but not in that of other organs, except for the phyllodes type of lesions, are discussed. Benign and malignant lesions of the soft tissues that occur in the stroma of other organs and are seen with some frequency in the prostate are also discussed. Few of the rarer soft tissue lesions are mentioned. Lesions and tumors with melanocytic differentiation, hematopoietic derivation, and germ cell tumors are described. It is hoped that this review will serve as a useful reference when encountering some of these lesions, all of which are referenced to their original and subsequent reports. Some non-English language references are also cited to reflect the international recognition of these lesions or to give credit to the author who first described the entity.

TNFR-associated factor family protein expression in normal tissues and lymphoid malignancies.

TNFR-associated factors (TRAFs) constitute a family of adapter proteins that associate with particular TNF family receptors. Humans and mice contain six TRAF genes, but little is known about their in vivo expression at the single cell level. The in vivo locations of TRAF1, TRAF2, TRAF5, and TRAF6 were determined in human and mouse tissues by immunohistochemistry. Striking diversity was observed in the patterns of immunostaining obtained for each TRAF family protein, suggesting their expression is independently regulated in a cell type-specific manner. Dynamic regulation of TRAFs was observed in cultured PBLs, where anti-CD3 Abs, mitogenic lectins, and ILs induced marked increases in the steady-state levels of TRAF1, TRAF2, TRAF5, and TRAF6. TRAF1 was also highly inducible by CD40 ligand in cultured germinal center B cells, whereas TRAF2, TRAF3, TRAF5, and TRAF6 were relatively unchanged. Analysis of 83 established human tumor cell lines by semiquantitative immunoblotting methods revealed tendencies of certain cancer types to express particular TRAFs. For example, expression of TRAF1 was highly restricted, with B cell lymphomas consistently expressing this TRAF family member. Consistent with results from tumor cell lines, immunohistochemical analysis of 232 non-Hodgkin lymphomas revealed TRAF1 overexpression in 112 (48%) cases. TRAF1 protein levels were also elevated in circulating B cell chronic lymphocytic leukemia specimens (n = 49) compared with normal peripheral blood B cells (p = 0.01), as determined by immunoblotting. These findings contribute to an improved understanding of the cell-specific roles of TRAFs in normal tissues and provide evidence of altered TRAF1 expression in lymphoid malignancies.

TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues.

TRAF-4 was discovered because of its expression in breast cancers and is a member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of putative signal-transducing proteins. In vitro binding assays demonstrated that TRAF-4 interacts with the cytosolic domain of the lymphotoxin-beta receptor (LT beta R) and weakly with the p75 nerve growth factor receptor (NGFR) but not with TNFR1, TNFR2, Fas, or CD40. Immunofluorescence analysis of TRAF-4 in transfected cells demonstrated localization to cytosol but not nucleus. Immunohistochemical assays of normal human adult tissues revealed prominent cytosolic immunostaining in thymic epithelial cells and lymph node dendritic cells but not in lymphocytes or thymocytes, paralleling the reported patterns of LT beta R expression. The basal cell layer of most epithelia in the body was very strongly TRAF-4 immunopositive, including epidermis, nasopharynx, respiratory tract, salivary gland, and esophagus. Similar findings were obtained in 12- to 18-week human fetal tissue, indicating a highly restricted pattern of expression even during development in the mammary gland, epithelial cells of the terminal ducts were strongly TRAF-4 immunopositive whereas myoepithelial cells and most of the mammary epithelial cells lining the extralobular ducts were TRAF-4 immunonegative. Of 84 primary breast cancers evaluated, only 7 expressed TRAF-4. Ductal carcinoma in situ (DCIS) lesions were uniformly TRAF-4 immunonegative (n = 21). In the prostate, the basal cells were strongly immunostained for TRAF-4, whereas the secretory epithelial cells were TRAF-4 negative. Basal cells in prostate hypertrophy (n = 6) and prostatic intraepithelial neoplasia (PIN; n = 6) were strongly TRAF-4 positive, but none of the 32 primary and 16 metastatic prostate cancer specimens examined contained TRAF-4-positive malignant cells. Although also expressed in some types of mesenchymal cells, these findings suggest that TRAF-4 is a marker of normal epithelial stem cells, the expression of which often ceases on differentiation and malignant transformation.

Expression and location of pro-apoptotic Bcl-2 family protein BAD in normal human tissues and tumor cell lines.

The BAD protein is a pro-apoptotic member of the Bcl-2 family whose ability to heterodimerize with survival proteins such as Bcl-X(L) and to promote cell death is inhibited by phosphorylation. Monoclonal antibodies were generated against the human BAD protein and used to evaluate its expression by immunoblotting and immunohistochemistry in normal human tissues and by immunoblot analysis of the National Cancer Institute anti-cancer drug screening panel of 60 human tumor cell lines. BAD protein was detectable by immunoblotting in many normal tissues, with testis, breast, colon, and spleen being among those with the highest steady-state levels. Immunostaining of tissues revealed many examples of cell-type-specific expression of BAD, suggesting dynamic regulation of BAD protein levels in vivo. In many types of normal cells, BAD immunoreactivity was associated with cytosolic organelles resembling mitochondria, suggesting that BAD is often heterodimerized with other Bcl-2 family proteins in vivo. The relative levels of BAD protein varied widely among established human tumor cell lines, with colon, lung, and melanomas generally having the highest expression. As a group, hematopoietic and lymphoid lines contained the least BAD protein. The BAD protein derived from 11 of 41 tumor lines that expressed this pro-apoptotic protein migrated in gels as a clear doublet, consistent with the presence of hyperphosphorylated BAD protein. Taken together, these findings define for the first time the normal cell-type-specific patterns of expression and intracellular locations of the BAD protein in vivo and provide insights into the regulation of this pro-apoptotic Bcl-2 family protein in human tumors.

Immunohistochemical analysis of in vivo patterns of expression of CPP32 (Caspase-3), a cell death protease.

The in vivo patterns of CPP32 (Caspase-3) gene expression were determined using an immunohistochemical approach and paraffin-embedded normal human tissues. A rabbit polyclonal antiserum was generated against recombinant human CPP32 protein and shown to be specific by immunoblot analysis of various human tissues and cell lines. CPP32 immunoreactivity was selectively found in certain cell types and was typically present within the cytosol, although occasional cells also contained nuclear immunostaining. CPP32 immunostaining was easily detected, for example, in epidermal keratinocyes, cartilage chondrocytes, bone osteocytes, heart myocardiocytes, vascular smooth muscle cells, bronchial epithelium, hepatocytes, thymocytes, plasma cells, renal tubule epithelium, spermatogonia, prostatic secretory epithelial cells, uterine endometrium and myometrium, mammary ductal epithelial cells, and the gastrointestinal epithelium of the stomach, intestine, and colon. In contrast, little or no CPP32 immunoreactivity was observed in endothelial cells, alveolar pneumocytes, kidney glomeruli, mammary myoepithelial cells, Schwann cells, and most types of brain and spinal cord neurons. Consistent with a role for CPP32 in apoptotic cell death, clear differences in the relative intensity of CPP32 immunostaining were noted in some shorter-lived types of cells compared to longer-lived, including (a) germinal center (high) versus mantle zone (low) B lymphocytes within the secondary follicles of lymph nodes, spleen, and tonsils; (b) mature neutrophils (high) versus myeloid progenitor cells (low) in bone marrow; (c) corpus luteal cells (high) versus follicular granulosa cells (low) in the ovary; and (d) prostate secretory epithelial cells (high) versus basal cells (low). These findings establish for the first time the cell type- and differentiation-specific patterns of expression of an interleukin-1beta converting enzyme/CED-3 (Caspase) family protease.

Lymphoid cell aggregates: a useful clue in the fine-needle aspiration diagnosis of follicular lymphomas.

Among the various types of lymphoma, follicular lymphoma (FL) is known to have significant limitations in cytologic diagnosis by the fine-needle aspiration (FNA) method. The diagnostic accuracy (DA) for non-Hodgkin's lymphoma (NHL) by FNA was evaluated by review of 82 cases of histologically proved NHL after prior FNA. The DA for all NHLs was 66% (54/82), and that for low-grade lymphomas, including small lymphocytic lymphoma, follicular small-cleaved cell lymphoma, and follicular mixed cell lymphoma, was 71% (12/17). The DA for FL was 69% (11/16). Review of individual surgical and cytologic materials from FLs revealed a tendency to show fibrosis in the cytologically false-negative group and diffuse areas of lymphoma in the true-positive group. The presence of "aggregation" of uniform lymphoid cells, probably due to cell adhesions with the support of dendritic reticulum cells, was seen in 55% of true-positive FL (6/11). In contrast, only 28% of true-positive diffuse large cell lymphomas (5/18) showed a mild degree of aggregation, and none of 7 cases of true-positive diffuse small-cleaved cell lymphoma showed this feature. The aggregation of cells was not pathognomonic of FL, but its presence with a homogeneous cellular constituent and the paucity of tingible-body macrophages helped us to predict FL. Also, it was a feature distinguishing FL from diffuse small-cleaved cell lymphoma (P = 0.025).

Immunohistochemical analysis of in vivo patterns of TRAF-3 expression, a member of the TNF receptor-associated factor family.

An immunohistochemical approach was used to explore the in vivo expression of TNF receptor-associated factor 3 (TRAF-3), a putative signaling protein that binds to the cytosolic domains of CD30, CD40, and lymphotoxin-beta receptors. TRAF-3 immunostaining was detected in many types of cells throughout the human body. TRAF-3 immunostaining was only rarely present in thymocytes but was found in the thymic epithelioreticular cells. Lymphocytes in the bone marrow were also typically TRAF-3 immunonegative, whereas myeloid progenitor cells and megakaryocytes were often TRAF-3 positive. Peripheral blood lymphocytes were mostly TRAF-3 immunonegative, while granulocytes were TRAF-3 immunopositive. Monocytes were strongly immunostained for TRAF-3, but macrophages in nodes typically contained little or no TRAF-3 immunoreactivity. Some lymphocytes within the germinal centers of secondary lymphoid follicles in normal and reactive nodes were TRAF-3 immunopositive, as were occasional interfollicular lymphocytes in the T cell regions of these organs, but most lymphocytes appeared to be TRAF-3 immunonegative or stained only weakly. Plasma cells, however, were strongly TRAF-3 positive. Stimulation of PBLs with anti-CD3 Ab induced marked increases in the steady state levels of TRAF-3 protein in vitro as determined by immunoblotting, while levels of TRAF-2 were unchanged, implying a dynamic regulation of TRAF-3 expression. The findings establish for the first time the cell type- and differentiation-specific patterns of expression of a member of the TRAF family of proteins.

Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers.

Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodies specific for the Bcl-2, Bax, Bcl-X, and Mcl-1 proteins in combination with immunohistochemical methods, we examined for the first time the expression of these bcl-2 family genes in 64 cases of adenocarcinoma of the prostate, including 10 Gleason grade 2 to 4 tumors, 21 grade 5 to 7 tumors, 17 grade 8 to 10 tumors, 8 lymph node metastases, and 8 bone metastases. In addition, 24 cases of prostatic intraepithelial neoplasia (PIN) or PIN coexisting with carcinoma were also evaluated. All immunostaining results were scored with regard to approximate percentage of positive tumor cells and relative immunostaining intensity. Expression of the anti-apoptotic protein Bcl-2 was present in 16 of 64 (25%) adenocarcinomas and tended to be more frequent in high grade tumors (Gleason grade 8 to 10; 41%) and nodal metastases (38%) than in lower grade (Gleason 2 to 7) primary tumors (16%; P < 0.05). Bcl-X was expressed in all 64 (100%) tumors evaluated. Bcl-X immunointensity was generally stronger in high grade primary tumors (grade 8 to 10) and metastases compared with PIN and low grade neoplasms (P < 0.0001). In addition, the proportion of specimens with > 50% Bcl-X-immunopositive tumor cells also was higher in advanced grade primary tumors (Gleason 8 to 10) and metastases than in PIN and low grade tumors (Gleason 2 to 7; P < 0.005). The anti-apoptotic protein Mcl-1 was expressed in 52 of 64 (81%) tumors, compared with only 9 of 24 (38%) cases of PIN (P < 0.001). In addition, the percentage of Mcl-1-positive cells was typically higher in Gleason grade 8 to 10 tumors and metastases than in PIN or lower grade tumors (P = 0.025). In contrast, the pro-apoptotic protein Bax was expressed in all prostate cancers evaluated, with high percentages of immunopositive cells and strong immunointensity typically occurring regardless of tumor grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate.

Keratinocyte growth factor causes proliferation of urothelium in vivo.

PURPOSE: To determine the effect of keratinocyte growth factor (KGF), a mesenchymally derived epithelial growth factor that can cause proliferation of pulmonary, gastrointestinal and mammary epithelia, on urothelium. MATERIALS AND METHODS: Recombinant human KGF was systemically administered to rats and Rhesus monkeys, and the proliferative effects on the bladder were evaluated. RESULTS: Keratinocyte growth factor causes proliferation of transitional epithelial cells. Proliferating cell nuclear antigen (PCNA) expression in rat bladder is dramatically increased along the basal layer of urothelium 1, 3, 7 and 14 days after daily injections of KGF. Incorporation of 5-bromodeoxyuridine (BrdU) at 7 and 14 days in the urothelium of KGF-treated rats parallels PCNA immunoreactivity and confirms that KGF increases DNA synthesis in urothelial cells. Urothelial cell proliferation is accompanied histologically by an increase in mitotic activity. Keratinocyte growth factor-induced PCNA expression is reversible upon cessation of KGF administration. Keratinocyte growth factor mRNA and receptor mRNA are detected by whole organ RNAase protection assays of the urinary bladder and the kidney of normal rats. Rhesus monkeys receiving KGF for 7 days demonstrate a dramatic incorporation of BrdU in the urothelium of the bladder and renal pelvis as well as in the collecting ducts of the kidney. CONCLUSION: Systemic administration of KGF causes rapid and striking proliferation of urothelium.

Immunohistochemical analysis of Mcl-1 protein in human tissues. Differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo.

The mcl-1 gene encodes an approximately 37-kd protein that has significant homology with Bcl-2, an inhibitor of programmed cell death that is expressed in many types of long-lived cells. In this study we determined the in vivo patterns of Mcl-1 protein production in normal human tissues by immunohistochemical means, using specific polyclonal antisera, and made comparisons with Bcl-2. Like Bcl-2, Mcl-1 immunostaining was observed in epithelial cells in a variety of tissues, including prostate, breast, endometrium, epidermis, stomach, intestine, colon, and respiratory tract. However, often the expression of mcl-1 and bcl-2 in complex epithelia occurred in gradients with opposing directions, such that Bcl-2 immunostaining tended to be higher in the less differentiated cells lining the basement membrane, whereas Mcl-1 immunostaining was more intense in the differentiated cells located in the upper layers of these epithelia. The in vivo patterns of mcl-1 and bcl-2 expression were also strikingly different in several other tissues as well. Within the secondary follicles of lymph nodes and tonsils, for example, germinal center lymphocytes were Mcl-1 positive but mostly lacked Bcl-2; whereas mantle zone lymphocytes expressed bcl-2 but not mcl-1. Intense Mcl-1 immunoreactivity was also detected in several types of neuroendocrine cells, including the adrenal cortical cells that are Bcl-2 negative, sympathetic neurons that also contain Bcl-2, a subpopulation of cells in the pancreatic islets, Leydig cells of the testis, and granulosa lutein cells of the ovarian corpus luteum but not in thyroid epithelium, which is strongly Bcl-2 positive. Little or no Mcl-1 was detected in neurons in the brain and spinal cord, in contrast to Bcl-2, which is present in several types of central nervous system neurons. Conversely, strong Mcl-1 immunostaining was found in cardiac and skeletal muscle, which contain comparatively less Bcl-2. Additional types of cells that are Bcl-2-negative but that expressed mcl-1 include chondrocytes and hepatocytes. These findings demonstrate that mcl-1 expression is widespread in vivo and imply that the Mcl-1 and Bcl-2 proteins fulfill different roles in the overall physiology of cell death regulation.

Fine Needle Aspiration Biopsy Cytology of Argyrophilic Carcinoma (Carcinoid Tumor) of the Breast.

Argyrophilic carcinoma of the breast, previously referred to as carcinoid tumor, is a rare form of ductal carcinoma that can be diagnosed by fine needle aspiration biopsy. This tumor is characterized by widespread cytoplasmic granules with affinity for reduced silver stains or argyrophilia. The tumor tends to occur in older women and behaves in a fashion similar to classic ductal carcinoma. The argyrophilia may reflect stored neurosecretory granules or, less frequently, mucinous or lactational changes. Carcinoid or other neuroendocrine syndromes are not observed.

Primary yolk sac tumor of the prostate in a patient with Klinefelter's syndrome.

Primary yolk sac (endodermal sinus) tumor of the prostate is extremely rare with only 2 cases reported in the literature. We describe a case of primary yolk sac tumor of the prostate in a man with Klinefelter's syndrome. Treatment included 4 courses of combination chemotherapy followed by retroperitoneal lymph node dissection, cystoprostatectomy and ileal conduit urinary diversion. We review the association of Klinefelter's syndrome with extragonadal germ cell tumor along with the management of this rare disease.

Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2.

The protein encoded by the bcl-2 gene is a regulator of programmed cell death and apoptosis. The cell survival-promoting activity of this protein is opposed by Bax, a homologous protein that forms heterodimers with Bcl-2 and accelerates rates of cell death. In this report, the in vivo patterns of bax gene expression were immunohistochemically assessed in the mouse, with a polyclonal antibody raised against a synthetic peptide corresponding to a unique region in the murine Bax protein. Direct comparisons were made with Bcl-2 by using anti-peptide antisera specific for the mouse Bcl-2 protein. The expression of bax was more widespread than bcl-2. For example, Bax immunoreactivity was present in the hepatocytes of the liver, the exocrine pancreas, and the renal tubule epithelial cells whereas Bcl-2 was absent from these tissues. Both the Bax and Bcl-2 proteins were present in several epithelia examined, including the small intestines, colon, breast, prostate, respiratory tract, and skin. The most intense Bax immunostaining was seen in cells located in the base of the crypts of the small intestinal mucosa, consistent with reports of high rates of spontaneous and inducible apoptosis in this region. Bcl-2 immunostaining was completely absent from these cells but was present in the absorptive epithelial cells of the small intestine. In contrast, Bax immunostaining in the colon tended to be stronger in the surface epithelial cells that had advanced up the crypts towards the lumen and that are destined for programmed cell death, whereas Bcl-2 immunoreactivity generally was stronger in the base of the colonic crypts. Similarly, bax expression in the gastric pits of the stomach occurred in a gradient such that higher levels of Bax immunostaining were found in the upper layers of gastric glands than in the lower regions. In addition, strong Bax immunostaining was detected in the androgen-dependent secretory epithelial cells of the prostate, whereas Bcl-2 was limited to the androgen-independent basal cells. Like Bcl-2, Bax was found in the thymic medulla but not the cortex, despite the propensity for immature cortical thymocytes to undergo apoptosis. Unlike Bcl-2, however, Bax immunostaining tended to be more intense in the germinal center lymphocytes of lymph nodes than in the interfollicular lymphocytes, consistent with the high rate of apoptotic cell death in the former.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunohistochemical analysis of in vivo patterns of Bcl-X expression.

The in vivo patterns of bcl-X gene expression were assessed in human and mouse tissues using an immunohistochemical approach. Polyclonal antisera were raised against synthetic peptides corresponding to amino acids 46-66 and 61-79 of the human Bcl-X protein and were shown to be specific for detection of human and mouse Bcl-X-L and Bcl-X-S proteins by immunoblotting. Bcl-X immunoreactivity was detected in a wide variety of cell types and was typically present in the cytosol in a punctate pattern suggestive of association with intracellular organelles. Among the cell types with prominent Bcl-X immunostaining were: (a) a variety of neuronal populations in the brain as well as sensory neurons in dorsal root ganglia; (b) cortical (but not medullary) thymocytes and activated lymphocytes and plasma cells in lymph nodes; (c) several types of cells in the bone marrow, including megakaryocytes, red cell precursors, and some types of differentiating myeloid cells; (d) reproductive tissues, including the spermatocytes and spermatids in the testes and germinal epithelium of the ovary; and (e) a variety of epithelial cells including mammary epithelium, the secretory epithelial and basal cells of the prostate, uterine endometrium, gastric and intestinal epithelial cells, renal tubule epithelium, and differentiated keratinocytes in the upper layers of the epidermis but not in the basal cells. In many cases, these patterns of Bcl-X expression were strikingly different from those reported previously for Bcl-2, suggesting that Bcl-X and Bcl-2 regulate cell life and death at different stages of cell differentiation through tissue-specific control of their expression.

Mucinous adenocarcinoma of the prostate and hormone sensitivity.

We report a case of mucinous adenocarcinoma of the prostate treated successfully with androgen ablation followed by laparoscopic lymphadenectomy and total perineal prostatectomy. This case demonstrates that mucinous adenocarcinoma of the prostate may be hormonally sensitive.

Role of DNA image cytometry in the follow-up of patients with urinary tract transitional cell carcinoma.

Detection of recurrent urinary tract transitional cell carcinoma (TCC) is a frequent diagnostic challenge in exfoliative cytology because of the difficulty in distinguishing reactive changes from low grade tumors. This study evaluated the role of DNA analysis by image cytometry (ICM) as a diagnostic aid to cytology. Eighty-seven urine samples from patients with a known history of transitional cell carcinoma were examined by both cytology and ICM, and the results were compared with concurrent surgical biopsy specimens and patients' follow-up data. Twenty-seven patients were also examined by cystoscopy, and the results were compared to those of DNA analysis, cytology and biopsy. Urine samples were cytocentrifuged and stained with Papanicolaou stain for general cytology and Feulgen stain for ICM. DNA ploidy and the proliferating cell fraction (SG2M) were measured using the CAS 200 image analyzer. Among the 87 specimens included in the study, 59 were from patients considered to have recurrent disease when urine was obtained. Of the 59 recurrences, 33 were detected by cytology, 50 by ICM and 50 by biopsy, resulting in 55%, 85% and 85% sensitivity, respectively. When combined, cytology and ICM detected 53 recurrences and achieved 90% sensitivity. Nine cases originally undetected by biopsy had abnormal DNA histograms and were found to have TCC on follow-up examination. All cases undetected by ICM were low grade lesions with DNA diploidy and low proliferation. Among the 27 patients examined by cystoscopy, 14 had recurrent disease; 5, 13 and 6 of those cases were detected by cystoscopy, DNA analysis and cytology, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Fine needle aspiration biopsy of palpable breast lesions. Review and statistical analysis of 1875 cases.

Fine needle aspiration biopsy (FNAB) is an increasingly accepted method for investigating palpable breast nodules. We reviewed our experience with a consecutive series of 1875 FNABs performed using 21 or 23 gauge butterfly needles. Correlation was made with histology (524 cases) or clinical follow-up (2-70 months). Cytological diagnoses utilized histopathological terminology and were categorized as: unsatisfactory (93 or 4.96%); no evidence of malignancy (1295 or 69.07%); atypical (183 or 9.76%); suspicious (42 or 2.24%); malignant (262 or 13.97%). Of the 1571 benign aspirates, 220 or 14% were followed by excisional biopsy because of clinical suspicion, atypia or hypocellularity. Of these aspirates, 198 were benign while 22 proved to be malignant (one in situ ductal, one intracystic papillary, two tubular, one cribriform, seven ductal nos, three in situ and five infiltrating lobular carcinomas, two large cell lymphomas). Malignancy was detected histologically in 12.9% of unsatisfactory, 3.06% of benign but often hypocellular, 8.16% of atypical, 97.62% of suspicious and 100% of malignant aspirates. Considering only histologically verified breast aspirates and including suspicious cytodiagnoses, FNAB had a sensitivity of 93.23%, a specificity of 99.50%, positive and negative predictive values of 99.62% and 90%, and an overall diagnostic accuracy of 95.61%. This series clearly shows that FNAB effectively evaluates palpable breast lesions when careful consideration is given to clinical judgement, specimen procurement, diagnostic criteria and a clinically relevant reporting style.