Biomedical subjects

Fernando U Garcia

Publications and source records attributed to Fernando U Garcia.

17 recordsLinked to original sources

PubMed2006

Heterogeneous breast tumoroids: An in vitro assay for investigating cellular heterogeneity and drug delivery.

Breast tumors are typically heterogeneous and contain diverse subpopulations of tumor cells with differing phenotypic properties. Planar cultures of cancer cell lines are not viable models of investigation of cell-cell and cell-matrix interactions during tumor development. This article presents an in vitro coculture-based 3-dimensional heterogeneous breast tumor model that can be used in drug resistance and drug delivery investigations. Breast cancer cell lines of different phenotypes (MDAMB231, MCF7, and ZR751) were cocultured in a rotating wall vessel bioreactor to form a large number of heterogeneous tumoroids in a single cell culture experiment. Cells in the rotating vessels were labeled with Cell Tracker fluorescent probes to allow for time course fluorescence microscopy to monitor cell aggregation. Histological sections of tumoroids were stained with hematoxylin and eosin, progesterone receptor, E-cadherin (E-cad), and proliferation marker ki67. In vitro tumoroids developed in this study recapture important features of the temporal-spatial organization of solid tumors, including the presence of necrotic areas at the center and higher levels of cell division at the tumor periphery. E-cad-positive MCF7 cells form larger tumoroids than E-cad-negative MDAMB231 cells. In heterogeneous tumors, the irregular surface roughness was mainly due to the presence of MDAMB231 cells, whereas MCF7 cells formed smooth surfaces. Moreover, when heterogeneous tumoroids were placed onto collagen gels, highly invasive MDAMB231 cell-rich surface regions produced extensions into the matrix, whereas poorly invasive MCF7 cells did not. The fact that one can form a large number of 1-mm tumoroids in 1 coculture attests to the potential use of this system at high-throughput investigations of cancer drug development and drug delivery into the tumor.

Breast Neoplasms↗

PubMed2006

Large-scale computations on histology images reveal grade-differentiating parameters for breast cancer.

BACKGROUND: Tumor classification is inexact and largely dependent on the qualitative pathological examination of the images of the tumor tissue slides. In this study, our aim was to develop an automated computational method to classify Hematoxylin and Eosin (H&E) stained tissue sections based on cancer tissue texture features. METHODS: Image processing of histology slide images was used to detect and identify adipose tissue, extracellular matrix, morphologically distinct cell nuclei types, and the tubular architecture. The texture parameters derived from image analysis were then applied to classify images in a supervised classification scheme using histologic grade of a testing set as guidance. RESULTS: The histologic grade assigned by pathologists to invasive breast carcinoma images strongly correlated with both the presence and extent of cell nuclei with dispersed chromatin and the architecture, specifically the extent of presence of tubular cross sections. The two parameters that differentiated tumor grade found in this study were (1) the number density of cell nuclei with dispersed chromatin and (2) the number density of tubular cross sections identified through image processing as white blobs that were surrounded by a continuous string of cell nuclei. Classification based on subdivisions of a whole slide image containing a high concentration of cancer cell nuclei consistently agreed with the grade classification of the entire slide. CONCLUSION: The automated image analysis and classification presented in this study demonstrate the feasibility of developing clinically relevant classification of histology images based on micro- texture. This method provides pathologists an invaluable quantitative tool for evaluation of the components of the Nottingham system for breast tumor grading and avoid intra-observer variability thus increasing the consistency of the decision-making process.

Journal Article↗

PubMed2006

Lipofuscin pigment can be used as a prognostic marker in prostatic adenocarcinoma.

Lipofuscin, known as the "wear and tear" pigment, is seen in cells undergoing regressive changes, the seminal vesicles and the ejaculatory ducts. It is also present in prostatic adenocarcinoma. The purpose of this study is to evaluate the prognostic significance of lipofuscin in prostatic adenocarcinoma. Lipofuscin was evaluated in 736 hematoxylin-eosin-stained slides from 60 conventional and whole-mounted consecutive radical prostatectomies from December 1996 to February 2002. The adenocarcinoma cases were divided into lipofuscin-positive group and lipofuscin-negative group. The Gleason score and pathologic stage were compared between the 2 groups. Percentage of cells positive for p53 and MIB-1 was also compared. Lipofuscin pigment was found in 17 (31%) of 60 prostatic adenocarcinomas as random, sparse, fine, yellow-brown intracytoplasmic granules staining positive for cathepsin D and negative for S-100 protein. Using logistic regression to exclude age as a confounding factor, lower Gleason scores and pathologic stages were demonstrated in the lipofuscin-positive group. There was also a significant difference between the 2 groups in tumor volume, degree of capsular invasion, and positive margins. The difference in seminal vesicle invasion and vascular invasion between the 2 groups was not statistically significant. Lipofuscin in prostatic adenocarcinoma correlates with both lower Gleason score and pathologic stage. Lipofuscin probably indicates slow cellular turnover as suggested by the low proliferation rate and p53 expression. The value of lipofuscin in biopsy as a predictor separating aggressive from indolent disease needs further investigation.

Adenocarcinoma↗

PubMed2006

Intraprostatic spermatozoa: zonal distribution and association with atrophy.

Intraprostatic spermatozoa (IS) have been demonstrated in only 2 articles in the literature reporting on postmortem prostates. Intraprostatic spermatozoa have not been previously described in radical prostatectomies. This is the first study that describes the presence of IS in radical prostatectomies with prostatic carcinoma (PC) and its association with atrophy. We examined whole mount sagittal sections from 69 consecutive radical prostatectomy cases for PC. A central section including the seminal vesicle ejaculatory duct urethra complex (SVEDU) from each case was stained with Berg's stain to identify spermatozoa and their location. The extent and the type of atrophy were assessed on the entire prostate by using a grid method. Eighteen cases (26.1%) revealed spermatozoa both in the SVEDU and in the prostate (IS) (group 1). Twenty-two cases (31.9%) showed spermatozoa exclusively in the SVEDU but not in the prostate (group 2). The remaining 29 cases (42.0%) had no spermatozoa in either site. Location of IS was 72.2% peripheral zone, 22.2% central zone, and 5.6% transitional zone. Intraprostatic spermatozoa were frequently seen accompanied by inflammatory infiltrate in the periglandular stroma. The extent of atrophy was greater in group 1 than in group 2 (25.7% versus 15.3%; P = .006). Postatrophic hyperplasia was seen more frequently in group 1 than in group 2 (72.2% versus 40.9%; P = .025). In conclusion, the frequency of IS is 26.1% when including all prostates and 45.0% when including prostates with evidence of residual ejaculate (spermatozoa in the SVEDU), more than previously reported. Intraprostatic spermatozoa are predominantly located in the peripheral zone similar to atrophy and PC. Prostates with IS have larger atrophic areas and increased frequency of postatrophic hyperplasia. The role of IS in the pathogenesis of prostate inflammation and atrophy should be investigated.

Adenocarcinoma↗

PubMed2006

Use of a new method in reaching consensus on the cause of cytologic-histologic correlation discrepancy.

Pathologists exhibit very poor agreement in adjudicating the cause of cytologic-histologic correlation discrepancies, which contributes to problems in designing interventions to reduce discrepancy frequency. In this observational study, we developed a visual method of adjudicating discrepancy cause, termed the No-Blame Box method, which consisted of initially assessing specimen interpretability by separately evaluating specimen quality and the presence of tumor. Five pathologists blindly adjudicated the cause of discrepancy in pulmonary specimens from 40 patients. The kappa statistic of all pathologist pairs in adjudicating discrepancy cause using the No-Blame Box method ranged from 0.400 to 0.796, indicating acceptable to excellent agreement. Pathologists ranged in their assessment of specimen interpretability from 13% to 20%, and in no case did all 5 pathologists concur that a specimen was interpretable. Most discrepancies resulted from pathologists diagnosing noninterpretable samples. Pathologists who used the No-Blame Box showed significant agreement in the adjudication of discrepancy cause.

Consensus↗

PubMed2005

Impaired homologous recombination DNA repair and enhanced sensitivity to DNA damage in prostate cancer cells exposed to anchorage-independence.

During metastases, cancer cells are temporarily exposed to the condition in which interactions with extracellular environment can be restricted (anchorage-independence). We demonstrate that the sensitivity of prostate cancer cell lines, DU145 and PC-3, to genotoxic treatment (cisplatin and gamma-irradiation) increased several folds when cells were forced to grow in anchorage-independence. This enhanced drug sensitivity was associated with a severe impairment of homologous recombination-directed DNA repair (HRR). The mechanism involves Rad51, which is the major enzymatic component of HRR. The protein level of Rad51 and its recruitment to DNA double-strand breaks (DSBs) were both attenuated. Rad51 deficiency in anchorage-independence was not associated with Rad51 promoter activity, and was not compensated by a constitutive overexpression of Rad51 cDNA. Instead, Rad51 protein level and its ability to colocalize with DSBs were restored in the presence of proteosome inhibitors, or when cells from the suspension cultures were allowed reattachment. Presented results indicate that anchorage-independence sensitizes prostate cancer cells to genotoxic agents; however, it also attenuates faithful component of DNA repair by targeting stability of Rad51. This temporal attenuation of HRR may contribute to the accumulation mutations after DNA damage, and possibly the selection of new adaptations in cells, which survived genotoxic treatment.

Cell Line, Tumor↗

PubMed2005

Diagnostic utility of p75 neurotrophin receptor (p75NTR) as a marker of breast myoepithelial cells.

We evaluated the low affinity neurotrophin receptor (p75NTR) as a marker of breast myoepithelial cells. Immunohistochemical staining for p75NTR was performed on paraffin sections of 122 malignant breast lesions, 28 benign lesions and the adjacent normal breast tissue. The staining pattern was compared to those of myosin heavy chain and p63. p75NTR immunostain was consistently positive and compatible with p63 and myosin immunoreactivity in the myoepithelial cells of the normal mammary gland, benign breast lesions (six usual ductal hyperplasias, six specimens with sclerosing adenosis, eight intraductal papillomas, six fibroadenomas), and carcinoma in situ (18 ductal carcinomas in situ, two noninvasive papillary carcinomas, two lobular carcinomas in situ). The luminal cells were negative for p75NTR, but rare positive cells were noticed in the solid areas of some of the usual ductal hyperplasias. Four of 64 invasive ductal carcinomas (6%) and all metaplastic carcinomas (n = 3, 100%) showed a variable degree of p75(NTR) positivity. No p75NTR expression was found in the malignant cells in all in situ carcinomas, invasive lobular carcinomas (n = 11), tubular carcinomas (n = 10), invasive papillary carcinomas (n = 6), mucinous carcinomas (n = 4), and medullary carcinomas (n = 2). No myosin immunoreactivity was seen in the luminal/tumor cells, but p63 pattern of staining in the luminal/tumor cells was quite similar to that of p75NTR. Although significant p75NTR immunoreactivity was noticed in the vessels, nerves, and stromal component of fibroadenomas, no difficulties in the evaluation of the immunostain of myoepithelial cells were encountered. Our study shows that p75NTR is a useful marker for breast myoepithelial cells and can be used to rule out invasive disease as well as to evaluate difficult for diagnosis sclerosing lesions. Our data suggest a role of neurotrophins in the development of fibroepithelial breast tumors and some of the breast carcinomas.

Adenocarcinoma↗

PubMed2005

Gastrointestinal neurofibromatosis: an unusual cause of gastric outlet obstruction.

Neurofibromatosis type-1 (NF-1), also known as von Recklinghausen disease, is a common autosomal dominant condition occurring in approximately 1/3000 births. NF-1 is known to be associated with gastrointestinal neoplasms in 2-25 per cent of patients. We report the first case of gastric outlet obstruction with perforation caused by neurofibroma in a patient with NF-1. The literature is reviewed, examining 61 previously reported cases of noncarcinoid gastrointestinal (GI) neoplasms in patients with NF-1 for symptoms, location, and types of neoplasms. Neoplasms were located most often in the small intestine (72%). Neurofibromas, found in 52 per cent of patients, were the most frequently diagnosed benign neoplasms followed by leiomyomas (13%), ganglioneurofibromas (9.8%), and gastrointestinal stomal tumor (GIST) (6.5%). Adenocarcinoma was present in 23 per cent of patients. Patients with NF-1 and GI symptoms are at risk for gastrointestinal neoplasms from which symptomatic patients are likely to experience significant morbidity.

Adult↗

PubMed2004

Evidence for prostate cancer-associated diagnostic marker-1: immunohistochemistry and in situ hybridization studies.

PURPOSE: The purpose of this study was to characterize a novel gene/protein associated with prostate cancer, termed prostate cancer-associated diagnostic marker-1 [PCADM-1 (Hu Y, Wang M, Garcia FU, Aoyaki K, Stearns ME. Identification of PCADM-1 as a novel diagnostic marker for prostate cancer, submitted for publication)]. EXPERIMENTAL DESIGN AND RESULTS: Immunological studies revealed that rabbit polyclonal antibodies generated against recombinant PCADM-1 specifically recognize the protein in crude protein extracts from a variety of prostate cancer cell lines (i.e., PC-3 ML, LNCaP, DU145, and CPTX-1532) and prostate cancer tissue. Combined immunolabeling and in situ hybridization studies demonstrated that PCADM-1 mRNA was expressed by the luminal epithelial cells of prostate cancer glands and was not expressed by high-grade prostatic intraepithelial neoplasia or HPV-MLC7 cells. Immunolabeling studies of tissue arrays from biopsies of archival material (n = 200 samples) confirmed that PCADM-1 was expressed by the luminal epithelial cells of prostate cancer. CONCLUSIONS: Taken together, the data suggest that PCADM-1 is a specific marker for human prostate cancer.

Antigens, Neoplasm↗

PubMed2004

Fine-needle aspiration of adult small-round-cell tumors studied with flow cytometry.

Immunophenotypic study is critical for the diagnosis of adult small-round-cell tumors (SRCTs). We describe three patients with Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) and one patient with neuroblastoma in which flow cytometry immunophenotyping (FCI) on the fine-needle aspirate (FNA) and bone marrow aspirate (BMA) demonstrated an abnormal population of cells that were CD45(-) and CD16/CD56(+). Four patients with mean age of 30 years, three male and one female, clinically suspicious for a lymphoma or SRCT are described. FNA, BMA, and biopsy specimens were obtained for routine cytologic and histologic evaluation. Fresh tissue was studied by FCI. In all cases, the cytology smears showed small cells with round nuclei, slightly irregular nuclear membranes, fine chromatin, and scant cytoplasm. FCI showed CD16/56(+) and CD45(-) neoplastic cells in all cases. In one case, 76% of these cells were CD99(+). The diagnoses of ES/PNET were confirmed by immunohistochemical, ultrastructural, and cytogenetic studies. ES/PNET in FNA and BMA can be efficiently and rapidly diagnosed by combining cytologic examination with FCI using a panel including CD45, CD16/56, and CD99.

12E7 Antigen↗

PubMed2004

Expression of a flt-4 (VEGFR3) splicing variant in primary human prostate tumors. VEGF D and flt-4t(Delta773-1081) overexpression is diagnostic for sentinel lymph node metastasis.

Utilizing a cDNA expression library established from human prostate PC-3ML tumor cells, we have cloned a truncated flt-4 gene, termed flt-4t(Delta773-1081). We have then utilized RNase protection and ELISA to measure the relative levels of VEGF B, C, D and flt-1, KDR, flt-4 and flt-4t(Delta773-1081) expression in freshly isolated benign prostatic hyperplasia or BPH tissue (n=21), primary prostate cancers (n=82) and matching sentinel lymph node metastases from stage T2a-T2b/T3 tumors (n=52). Comparisons of the primary tumors with BPH showed that there was a significant upregulation of VEGF-B (P=0.003), VEGF D (P=0.005), flt-1 (P=0.003), KDR (P=0.002), flt-4 (P=0.007), and flt-4t(Delta773-1081) (P=0.001), but not VEGF-C (P=0.543). There was no correlation between VEGF-B and its receptor flt-1 (P=0.545), or VEGF-C and flt-4 (P=0.16) and KDR (P=0.23) receptor expression in tumor specimens. Conversely, there was no significant relationship between VEGF-D and the flt-4t(Delta773-1081) receptor (P=0.516) expression. Statistical analysis further showed that there was no significant correlation between VEGF-B, VEGF-C, VEGF-D, flt-1, KDR, flt-4 and flt-4t(Delta773-1081) with patient age (P>0.10), stage (P>0.10), PSA value (P>0.15) or tumor size (P>0.15). Likewise, there was no significant correlation between VEGF-B, VEGF-C, flt-1, KDR, and flt-4 with Gleason score (P>0.15). In comparison, flt-4t(Delta773-1081) levels clearly increased significantly in Gleason score 7 and Gleason score 8-10 tumors as well as in stage T2a-T2b/T3 tumors. The studies were extended to compare gene expression profiles in T2a-T2b and T3 tumors with (n=26) and without (n=26) matching sentinel lymph node metastases. The data showed that VEGF D and flt-4t(Delta773-1081) expression levels were significantly elevated in primary tumors with sentinel lymph node involvement compared to those lacking lymph node involvement (P>0.0022 and 0.006, respectively). These data suggest that targeting VEGF D and flt-4t(Delta773-1081) receptors may be particularly effective in the prevention of lymph node metastases.

Alternative Splicing↗

PubMed2003

Interleukin 10 blocks matrix metalloproteinase-2 and membrane type 1-matrix metalloproteinase synthesis in primary human prostate tumor lines.

Insulin-like growth factor (IGF) I has been shown previously to up-regulate matrix metalloproteinase-2 (MMP-2) production, whereas the interleukin (IL) 10/IL-10 receptor axis has been found to down-regulate MMP-2 synthesis in tumor cells. In this paper, we showed that IL-10 activation of the IL-10 receptor blocked MMP-2 and membrane type 1 (MT1) -MMP transcription and protein synthesis in nonimmortalized primary human prostate cell strains (i.e., HPCA-10a and HPCA-10c) derived from high-grade cancer. Northern blots, Western blots, and ELISAs showed that IL-10 suppressed IGF-I induction of MMP-2 and MT1-MMP mRNA synthesis in these cell strains (P < 0.001). Inhibition studies with IL-10 and IGF-I receptor antibodies plus transfections experiments with IL-10 sense, and IGF-I receptor antisense constructs confirmed these results. Finally, transient transfection experiments and chloramphenicol acetyltransferase assays with different regions of the 5' promoter region of the MMP-2 gene (-1659 to -555 bp) additionally showed that IGF-I stimulated p53-dependent plasmid catecholamine acetyltransferase activity and that IL-10 blocked IGF-I-induced plasmid catecholamine acetyltransferase activity. Electrophoretic mobility shift assays revealed that IL-10 induced protein(s) binding to a putative "silencer element" (-1309 to -555 fragment) downstream of the p53 binding site (-1649 to -1640). The data show that IL-10 blocks IGF-I activation of MMP-2 and MT1-MMP mRNA expression and protein synthesis in primary prostate cell strains.

Binding Sites↗

PubMed2002

Prostate cryoablation: a scientific rationale for future modifications.

This investigation was designed to identify potential directions for future modification of the percutaneous prostate cryoablation procedure. An analysis of prostate cancer location and volume in radical prostatectomy specimens was performed to evaluate the potential clinical consequences of these proposed modifications. A list of recommendations for improvements in the prostate cryoablation procedure was compiled from informal discussions held with participants in 9 training courses and conferences on prostate cryoablation over 18 months. Subsequently, a population of 112 consecutive, sagittally sectioned whole-mount radical prostatectomy samples was evaluated for prostate cancer volume, number of individual foci, and location to examine the disease-specific outcomes of these proposed modifications. The most common areas for potential alterations in the current cryoablation technique include modifications that would further simplify the procedure, continue to reduce real and perceived toxicity, and augment efficacy. Importantly, modifications designed to reduce treatment side effects could conflict with efforts designed to improve eradication of prostate cancer. Pathologic analysis revealed multifocal cancer in 79.5% of the samples, with 66% of cases exhibiting cancer within 5 mm of the urethra. The median volume of the index cancer was 1.6 cm3, whereas the median volume of the smaller ancillary lesions was 0.3 cm3. Prostate parenchymal-sparing alterations, proposed to reduce incontinence and erectile dysfunction by targeting the index cancer, would likely eradicate clinically significant cancer in 79% of men. The recent enthusiasm for prostate cryoablation as a reasonable minimally invasive treatment option for men with clinically localized cancer is likely to result in modifications of the established surgical technique. Knowledge of the anatomic location and cancer volume within the prostate gland is an important adjunct to planning such alterations. It is possible that parenchymal-sparing modifications to total gland prostate cryoablation can eradicate clinically significant cancer in most men, with a reduction in toxicity and cost.

Adenocarcinoma↗

PubMed2002

Use of MIB-1 in the assessment of esophageal biopsy specimens from patients with gastroesophageal reflux disease in well- and poorly oriented areas.

MIB-1, a proliferation marker may be useful in the assessment of esophageal biopsy specimens for gastroesophageal reflux disease (GERD). Forty-five hematoxylin and eosin-stained esophageal biopsy specimens were histologically assessed for basal zone height, papillary length, and inflammatory cell infiltrate and classified as 10 normal and 35 esophagitis. The percentage of MIB-1-positive area (MIB-1% area) was measured on immunostained sections using image analysis (CAS 200) in the basal half of well-oriented areas and adjacent to five cross-sectioned papillae (c-pap) in poorly oriented areas. The cell layer of the MIB-1-positive cell furthest from the basal layer of the c-pap was also noted. MIB-1% area was significantly greater in both well- and poorly oriented areas of esophagitis biopsy specimens compared with normal biopsy specimens. MIB-1 positivity in the basal half and c-pap were correlated (r = 0.43, p = 0.017). MIB-1 expression correlated with basal zone height and eosinophil infiltrate (r = 0.61, p < 0.001; r = 0.32, p = 0.03, respectively). The cell layer with positive cells furthest from c-pap in normal and esophagitis biopsy specimens was two and six layers, respectively. Using 31% as a threshold to detect abnormal findings, the MIB-1 sensitivity/specificity and positive predictive value in the basal half and c-pap were 86, 70, 91% and 80, 80, 94%, respectively. In summary, MIB-1 staining correlates with basal zone hyperplasia and eosinophil infiltrate seen in GERD. MIB-1 staining can be assessed both in well- and poorly oriented areas as MIB-1% areas. Alternatively simply finding MIB-1 positive cells more than three cell layers from the basal layer is abnormal and consistent with GERD.

Biopsy↗

PubMed2002

Cholesterol granuloma of the maxillary sinus.

Cholesterol granuloma is usually associated with chronic middle ear disease and is common in the mastoid antrum and air cells of the temporal bone. It has also been reported in other parts of the skull, such as the frontal and maxillary sinuses and orbit. Cholesterol granuloma is rare in the paranasal sinuses. We report a new case of cholesterol granuloma in the maxillary sinus of a 38-year-old man who underwent surgical excision. We also review the literature and discuss the mechanism of development for this lesion. The resected specimen showed fragments of respiratory mucosa with cholesterol clefts surrounded by multinucleated foreign-body giant cells. Some multinucleated foreign-body giant cells showed asteroid bodies. Hemorrhagic areas, hemosiderin-laden macrophages, chronic inflammatory cells, and dilated lymphatics vessels were seen as well. Increased intrasinus pressure due to drainage obstruction may affect venous and lymphatic drainage from the sinus cavity, leading to venule microhemorrhages while still allowing arterial blood into the sinus mucosa and further contributing to a large localized hemorrhage. Lymphatic drainage may be insufficient to completely remove the lipid components of the red blood cells, and the lipid accumulation may contribute to the formation of cholesterol crystals and their esters.

Adult↗

PubMed2002

Expression of cell-cycle-regulated proteins pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) in prostatic gland adenocarcinoma.

PURPOSE: The quest for prognostic molecular markers in prostatic carcinoma is still in progress. Many proteins have already been screened by immunohistochemistry with the aim to find the most reliable indicator of progressive disease. In this study, we evaluated the expression of pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) by immunohistochemistry in 24 prostate carcinomas compared with the paired expression of normal prostates. EXPERIMENTAL DESIGN: Expression of the different proteins in normal and pathological specimens was evaluated by the Wilcoxon test. A matrix of correlation (Spearman coefficient) was used to evaluate the possible association in expression among the different proteins. Logistic regression analysis was used to test the multivariable prognostic value of the levels of protein expression for the probability of disease development. RESULTS: p53 and Ki-67 (MIB-1) showed a higher expression in cancer than in normal tissue (P = 0.006 and <0.001, respectively). pRb2/p130, p107, and p27(kip1) showed an overall lower expression in cancer, but the difference between cytoplasmic and nuclear expression was always higher for cancer (Ps, from <0.001 to 0.016). mdm-2 expression was lower in cancer, but the difference between cytoplasmic and nuclear expression was not significant (P = 0.571) when compared with that in normal tissue. A positive correlation between p27 and pRb2/p130 levels expressed, in normal and cancer counterparts in the same sample, as the difference between cytoplasmic and nuclear protein concentrations (P = 0.045) was found. Additionally, p107 expression showed an inverse correlation with Ki-67 (MIB-1) expression in the most aggressive tumors (P = 0.046). Logistic regression output showed that Ki-67 (MIB-1) and pRb2/p130 (expressed as differences between cytoplasmic and nuclear concentrations) were the variables associated with a higher risk of cancer. The highest value was reported for Ki-67 (MIB-1) (odds ratio, 2.11), followed by pRb2/p130 (odds ratio, 1.01). pRb2/p130 alone was associated with a sensitivity (rate of cases having a posterior probability of disease >/=0.5) of 61% with a false positive rate of 22%. Ki-67 (MIB-1) alone yielded a sensitivity of 69% and a false positive rate of 14%. The combined model (Ki-67 + pRb2/p130) yielded a sensitivity of 83% with a false positive rate of 17%. Interestingly, one specimen in which we also found a high-grade prostatic intraepithelial neoplasia showed the progressive loss of pRb2/p130 from normal prostatic cells to prostatic intraepithelial neoplasia cells, suggesting that in prostatic cancer, lack of expression of the tumor suppressor gene pRb2/p130 could be involved in the progression of the disease, from an early stage. CONCLUSIONS: This study showed that all of the proteins but mdm-2 were expressed at a different rate in normal and pathological prostate specimens. Multivariate analysis showed that pRb2/p130 and p107 may be involved in the pathogenesis and progression of prostate cancers, and that the expression of the retinoblastoma-related protein pRb2/p130 along with Ki-67 (MIB-1), expressed as differences between cytoplasmic and nuclear concentrations, could be considered new parameters to be evaluated in discriminating patients at a higher risk for prostate cancer.

Adenocarcinoma↗

PubMedDate not supplied

Nodular myofibroblastic stromal hyperplasia of the mammary gland as an accurate name for pseudoangiomatous stromal hyperplasia of the mammary gland.

Pseudoangiomatous stromal hyperplasia (PASH) of the mammary gland is a well-known benign localized form of stromal overgrowth with probable hormonal etiology. We describe the histologic findings and immunohistochemistry of two cases. Two women, 16 and 58 years old, presented with a breast mass and underwent surgical excision. Grossly, they consisted of a well-circumscribed, rubbery tissue with a solid white-tan homogeneous cut surface. One of the cases showed focal cystic areas. Histologically the lesion showed a proliferation of the collagenous stroma with varying degrees of density, and hyalinization with many pseudovascular slit-like anastomosing spaces lined by spindle cells with scant cytoplasm and bland chromatin. The spindle cells lining the spaces were strongly reactive for vimentin and weakly reactive for CD34, actin, and desmin. They were negative for factor VIII, S-100, and pankeratin. In PASH, the "pseudoangiomatous" term describes a recognizable pattern but does not describe the tumor's histologic nature. We propose the name nodular myofibroblastic hyperplasia of the mammary stroma as a more accurate name.

Adolescent↗