Biomedical subjects

N Weidner

Publications and source records attributed to N Weidner.

At least 91 records · Page 5Linked to original sources

PubMed1993

Tumor angiogenesis: review of current applications in tumor prognostication.

The first requirement of a new prognostic indicator is that it should possess a clear biological significance. Indeed, much evidence shows that tumor growth and metastasis depend on neovascularization. Tumor angiogenesis (TA) refers to the growth of new vessels toward and within the tumor; unless tumor neovascularization occurs, cell proliferation reaches a steady state, and the tumor grows no larger than about 2 mm greatest diameter. Moreover, for tumor cells to metastasize, they must gain access to the vasculature from the primary tumor, survive the circulation, localize in the target organ, and induce angiogenesis in that target organ. TA is necessary both at the beginning and at the end of the metastatic cascade of events. Recently, my colleagues and I showed that a statistically significant correlation exists between incidence of metastases and microvessel density (MVD) of primary invasive breast carcinomas. Now, subsequent studies have shown that the association of prognosis with MVD exists not only in breast carcinoma but also in non-small-cell lung carcinoma, prostate carcinoma, and head-and-neck carcinoma. This article reviews the concepts and mechanisms of TA, the evidence supporting its role in growth and metastasis of solid tumors, and how measuring MVD within invasive tumors correlates with factor VIII-related antigen, blood vessel.

Humans↗

PubMed1993

Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma.

Tumor growth and metastasis require angiogenesis; and microvessel density, a measure of tumor angiogenesis, correlates with metastasis in breast and lung carcinoma. To determine how microvessel density correlated with metastasis in prostate carcinoma, we counted microvessels within the initial invasive carcinomas of 74 patients (29 with metastasis, 45 without). Microvessels were highlighted by immunostaining endothelial cells for factor VIII-related antigen. Without knowledge of the patient's cancer stage, microvessels were counted in a 200 field (0.739 mm2) in the most active areas of neovascularization. The mean microvessel count in tumors from patients with metastases was 76.8 microvessels per 200 field (median, 66; standard deviation, 44.6). The counts within carcinomas from patients without metastasis were significantly lower, 39.2 (median, 36; standard deviation, 18.6) (P < 0.0001). Microvessel counts increased with increasing Gleason's score (P < 0.0001), but this increase was present predominantly in the poorly differentiated tumors. Although Gleason's score also correlated with metastasis (P = 0.01), multivariate analysis showed that Gleason's score added no additional information to that provided by microvessel count alone. Assay of microvessel density within invasive tumors may prove valuable in selecting patients for aggressive adjuvant therapies in early prostate carcinoma.

Adult↗

PubMed1993

Concordance of DNA content between prostatic intraepithelial neoplasia and concomitant invasive carcinoma. Evidence that prostatic intraepithelial neoplasia is a precursor of invasive prostatic carcinoma.

It has been postulated that prostatic intraepithelial neoplasia (PIN) is a precursor lesion to invasive carcinoma in the prostate, yet there has been little direct evidence for this relationship. Therefore, we studied the DNA content of the epithelial cells in PIN lesions with accompanying invasive carcinoma in seven cases. DNA content of nuclei in Feulgen-stained tissue sections was performed using the CAS200 System (Cell Analysis Systems Inc, Elmhurst, Ill), with normal and hyperplastic glands serving as controls for diploid DNA content. In four cases, the cells of both lesions (PIN and invasive carcinoma) contained only diploid DNA; in one case, an additional aneuploid tumor stem line was present only in the invasive component; and in two cases, both PIN and carcinoma cells contained aneuploid cells having similar DNA content. The concordance of DNA content between PIN and invasive carcinoma in these cases provides evidence that PIN is a precursor lesion for invasive carcinoma.

Adenocarcinoma↗

PubMed1992

Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.

BACKGROUND: Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE: This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS: In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS: There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS: Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS: Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.

Adult↗

PubMed1992

Pleomorphic variant of invasive lobular carcinoma of the breast.

Infiltrating lobular carcinoma (ILC) of the classic type is well recognized; less well appreciated is a group of variant forms of ILC, which includes solid, alveolar, mixed, apocrine, signet-ring, histiocytoid, and tubulolobular variants. In addition, Page et al (Diagnostic Histopathology of the Breast, Churchill Livingstone, 1987, pp 219-226) recently have emphasized the pleomorphic variant of ILC, which demonstrates the infiltrating pattern of classic ILC; however, the nuclei are more pleomorphic and have features that may overlap with those of infiltrating duct carcinoma. To determine whether pleomorphic ILC shows significant prognostic differences from classic ILC, we reviewed the clinical courses of 25 patients with classic ILC and compared them with 16 patients with pleomorphic ILC. The major determinant in placing ILC into the pleomorphic category was the presence of nuclei of nuclear grade 2 or 3. All classic ILCs had nuclei of grade 1 by the Scarff-Bloom-Richardson criteria. Survival to recurrence was significantly worse (P less than or equal to .05) for the patients with pleomorphic ILC at lengths of survival greater than 30 months. In addition, node-negative patients with pleomorphic ILC were four times more likely to experience recurrence than node-negative patients with classic ILC; those with positive nodes and pleomorphic histology were 30 times more likely to experience recurrence. Although there appeared to be a trend toward decreased overall length of survival for those patients with pleomorphic ILC when compared with patients with classic ILC, this difference was not statistically significant.

Adult↗

PubMed1992

Mast-cell phenotype in indolent forms of mastocytosis. Ultrastructural features, fluorescence detection of avidin binding, and immunofluorescent determination of chymase, tryptase, and carboxypeptidase.

The factor(s) that causes excessive mast cell (MC) proliferation in indolent forms of mastocytosis is not known, nor is it known whether that proliferation is a regulated clonal expansion or merely a non-neoplastic hyperplasia. Human MCs display phenotypes that depend on the microenvironment. Thus, if the phenotype of MCs in mastocytosis lesions is determined to be abnormal for that tissue site (and therefore the MCs are refractory to microenvironmental signals) then a clonal process would be suggested. The authors determined the phenotypes of MCs from the lesional skin of 17 patients with indolent mastocytosis and the bone marrows of 9 patients. They compared them with the phenotypes of MCs from the lesional skin of 8 patients with various dermatitides, the skin of 2 patients with idiopathic anaphylaxis, and the breast skin of 15 control patients. MCs from all the skin specimens showed the characteristic skin MC phenotype, with predominantly scroll-poor granules by ultrastructure and containing tryptase and chymase by immunofluorescence detection (the MCTC immunophenotype). The skin MCs of each patient bound avidin and contained carboxypeptidase by immunofluorescence detection. MCs from the bone marrow of patients with indolent mastocytosis, the source of progenitors, also showed the scroll-poor and MCTC phenotypes. These findings do not support an unregulated clonal expansion in indolent forms of mastocytosis. They are consistent with a non-neoplastic hyperplasia or possibly a clonal process in which MCs remain responsive to microenvironmental regulation.

Avidin↗

PubMed1991

Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors.

BACKGROUND: Malignant soft-tissue tumors often present substantial diagnostic challenges. Chromosome aberrations that might be diagnostic have been identified in some types of soft-tissue tumors, but the overall frequency and diagnostic relevance of these aberrations have not been established. METHODS: We attempted to determine the karyotypes of a series of 62 consecutive, unselected malignant spindle-cell or small round-cell soft-tissue tumors (from 46 adults and 16 children) after direct harvesting of cells or short-term culture. All tumors were examined independently by immunohistochemical staining in addition to routine light-microscopical evaluation, and all but two tumors were examined by electron microscopy. RESULTS: Metaphases were obtained from 61 of the 62 tumors, and clonal chromosome aberrations were identified in 55 (89 percent). In the six tumors that yielded metaphases but lacked apparent clonal aberrations, the normal metaphases were found to originate from non-neoplastic stromal elements within the tumor specimens. Thus, all tumors in which karyotyping was successful contained clonal chromosome aberrations. Forty of 62 tumors (65 percent) contained clonal chromosome aberrations that either suggested or confirmed a specific diagnosis; in 15 of these tumors (24 percent of all tumors), the aberrations were important in establishing the final diagnosis. Cytogenetic analyses were particularly informative about small round-cell tumors from children: 8 of 14 round-cell tumors contained diagnostically important chromosome aberrations. Using the combined approaches of light and electron microscopy, immunohistochemistry, and cytogenetics, we established an unambiguous diagnosis for 60 of 62 tumors. CONCLUSIONS: Cytogenetic analyses reveal clonal chromosome aberrations in virtually all malignant soft-tissue tumors. These clonal chromosome aberrations, particularly in small round-cell tumors in children, often have diagnostic relevance.

Adult↗

PubMed1991

Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma.

BACKGROUND: Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without). METHODS: Using light microscopy, we highlighted the vessels by staining their endothelial cells immunocytochemically for factor VIII. The microvessels were carefully counted (per 200x field), and their density was graded (1 to 4+), in the most active areas of neovascularization, without knowledge of the outcome in the patient, the presence or absence of metastases, or any other pertinent variable. RESULTS: Both microvessel counts and density grades correlated with metastatic disease. The mean (+/- SD) count and grade in the patients with metastases were 101 +/- 49.3 and 2.95 +/- 1.00 vessels, respectively. The corresponding values in the patients without metastases were significantly lower--45 +/- 21.1 and 1.38 +/- 0.82 (P = 0.003 and P less than or equal to 0.001, respectively). For each 10-microvessel increase in the count per 200x field, there was a 1.59-fold increase in the risk of metastasis (95 percent confidence interval, 1.19 to 2.12; P = 0.003). The microvessel count and density grade also correlated with distant metastases. For each 10-microvessel increase in the vessel count per 200x field, there was a 1.17-fold increase in the risk of distant metastasis (95 percent confidence interval, 1.02 to 1.34; P = 0.029). CONCLUSIONS: The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.

Adult↗

PubMed1991

An endometrial stromal sarcoma with clonal cytogenetic abnormalities.

Cytogenetic analysis of a low-grade metastatic endometrial stromal sarcoma in a 58-year-old woman revealed translocations involving both homologues of chromosome 7 with chromosomes 13 and 17, respectively, and an interstitial deletion of the long arm of chromosome 11. The karyotype of the tumor was 46,XX,t(7;13)(q11.1;p13),t(7;17)(p21;q12),del(11)(q13q21).

Chromosome Deletion↗

PubMed1991

Multiple and complex abnormalities in a case of alveolar soft-part sarcoma.

Chromosomal analysis of two pulmonary metastases from a 25-year-old male with alveolar soft-part sarcoma of the right lower extremity revealed multiple and complex chromosomal abnormalities. The rearrangements included deletions and translocations affecting chromosomes 1, 2, 3, 10, 11, 14, 15, and 16. Trisomy of chromosome 12 and loss of chromosome 17 was also observed.

Adult↗

PubMed1991

Granulomatous prostatitis and poorly differentiated prostate carcinoma. Their distinction with the use of immunohistochemical methods.

Granulomatous prostatitis and poorly differentiated prostate carcinoma can mimic each other both clinically and histologically. To develop criteria useful in resolving problem cases, the authors compared the reactivities of these conditions (nine cases of granulomatous prostatitis and six cases of poorly differentiated carcinoma) with a panel of antibodies to cytokeratin (AE1/3), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), lysozyme, antimacrophage M, and leukocyte common antigen (LCA). In granulomatous prostatitis, histiocytes were not immunoreactive for PAP, PSA, or cytokeratin; however, histiocytes reacted to lysozyme in nine of nine cases, antimacrophage M in seven of nine cases, and LCA in one of nine cases. Tumor cells from all six carcinoma cases reacted with PAP, PSA, and cytokeratin; all failed to react with lysozyme, LCA, and antimacrophage M. The authors conclude that granulomatous prostatitis and poorly differentiated carcinoma can be reliably distinguished with immunohistochemical methods.

Aged↗

PubMed1991

Ultrastructural and immunohistochemical characterization of normal mast cells at multiple body sites.

This article reviews the ultrastructural and immunohistochemical features of normal human mast cells (MC) at multiple tissue sites. Current literature indicates that granules containing discrete scrolls (scroll-rich morphology) are frequent in MC from bowel mucosa and lung, locations where the majority of MC show only tryptase immunoreactivity (MC(T)). In contrast, most MC from skin, breast parenchyma, axillary lymph nodes, and bowel submucosa are characterized by scroll-poor morphology (that is, granules are rimmed by incomplete scrolls forming parallel lamellae and containing central, amorphous granular material or grating/lattice-like structures) and show both tryptase and chymase immunoreactivity (MC(TC)). MC having granules with both scroll-rich and scroll-poor features can occur in all tissue sites, and an occasional MC, especially in lung and bowel, may show only chymase immunoreactivity (MC(C)). Chymase immunoreactivity in MC also is closely associated with avidin binding and carboxypeptidase reactivity. We conclude that there is ultrastructural and immunophenotypic diversity among normal human MC, although certain forms predominate in specific tissue environments. In skin, breast tissue, axillary lymph nodes, and bowel submucosa MC tend to have scroll-poor granules and stain for avidin, chymase, tryptase, and carboxypeptidase, whereas, in lung and bowel mucosa MC granules tend to be scroll-rich and stain only for tryptase with currently available reagents.

Avidin↗

PubMed1991

Lobular carcinoma in situ: mammographic-pathologic correlation of results of needle-directed biopsy.

The mammographic and histologic findings were reviewed in 41 consecutive cases of isolated lobular carcinoma in situ (LCIS) unassociated with any malignant diagnosis. Thirty-one needle-directed breast biopsies were performed to evaluate clustered microcalcifications. In 24 of the 31 cases, the calcifications were found in areas of benign breast disease, with LCIS representing a separate process. In the few cases in which microcalcifications were seen in association with LCIS, a greater number of similar calcifications were present in adjacent benign disease. Soft-tissue abnormalities necessitating the performance of a biopsy represented benign foci, except in one patient with LCIS in and adjacent to a fibroadenoma. The authors conclude that LCIS has no characteristic mammographic features. LCIS is detected as an incidental finding at breast biopsy, with the mammographic abnormality predominantly reflecting a benign process.

Adult↗

PubMed1991

Lineage-restricted clonality in biphasic solid tumors.

Cytogenetic analysis of two pulmonary chondroid hamartomas and nine breast adenofibromas revealed clonal chromosome aberrations in both hamartomas and in four breast tumors. To determine lineage of the cells with chromosome aberrations, a combined immunohistochemical/cytogenetic approach was developed that enabled simultaneous ascertainment of cytogenetic aberrations and immunohistochemical features in individual cells. Immunohistochemical/cytogenetic evaluation of one hamartoma and two adenofibromas demonstrated that neoplastic proliferation, in each case, was confined to the mesenchymal (stromal) component, whereas epithelial cells appeared to be reactive. Cytogenetically abnormal short-term cultures of the remaining hamartoma and another of the breast adenofibromas were composed entirely of mesenchymal elements, indicating mesenchymal clonality in those tumors as well. Our findings support redesignation of pulmonary chondroid hamartomas as 'pulmonary chondromas' and suggest that carcinomas developing within fibroadenomas arise from reactive epithelial proliferation. Combined immunohistochemical/cytogenetic analysis might be useful in the development of novel therapeutic approaches that selectively target neoplastic populations within solid tumors.

Adenocarcinoma↗

PubMed1991

Localization of nuclear matrix proteins (NMPs) in multiple tissue types with NM-200.4 (an antibody strongly reactive with NMPs found in breast carcinoma).

Nuclear matrix proteins (NMP) are nonhistone proteins found in the nucleus of many eukaryotic cells. Furthermore certain NMPs are reported to be cell-type specific and expressed differentially by malignant cells. To study the specificity of NM-200.4 (an antibody reactive to NMPs extracted from cultured breast carcinoma cells of the T-47D line), cancers and benign tissues from multiple body sites were surveyed. All 17 breast carcinomas showed strong reactivity to tumor cell nuclei. Also nuclei from one of two lung carcinomas, a papillary thyroid carcinoma, an ovarian fibroma, and a lymphoma were strongly reactive. One leiomyosarcoma and a dermoid cyst were negative. Although 1 benign breast with duct hyperplasia showed moderate reactivity, only 1 of 10 benign breast biopsies without hyperplasia showed reactivity. Three of 4 skin biopsies, 2 liver biopsies, 6 of 9 kidney biopsies, and 5 of 10 gastrointestinal mucosal biopsies showed reactivity in benign nuclei. It is concluded that, although breast carcinoma nuclei showed the most consistent reactivity for NM-200.4, both benign and malignant nuclei from other body sites also show reactivity.

Animals↗

PubMed1991

Ultrastructural and immunohistochemical characterization of normal mast cells at multiple body sites.

This article reviews the ultrastructural and immunohistochemical features of normal human mast cells (MC) at multiple tissue sites. Current literature indicates that granules containing discrete scrolls (scroll-rich morphology) are frequent in MC from bowel mucosa and lung, locations where the majority of MC show only tryptase immunoreactivity (MCT). In contrast, most MC from skin, breast parenchyma, axillary lymph nodes, and bowel submucosa are characterized by scroll-poor morphology (that is, granules are rimmed by incomplete scrolls forming parallel lamellae and containing central, amorphous granular material or grating/lattice-like structures) and show both tryptase and chymase immunoreactivity (MCTC). MC having granules with both scroll-rich and scroll-poor features can occur in all tissue sites, and an occasional MC, especially in lung and bowel, may show only chymase immunoreactivity (MCC). Chymase immunoreactivity in MC also is closely associated with avidin binding and carboxypeptidase reactivity. We conclude that there is ultrastructural and immunophenotypic diversity among normal human MC, although certain forms predominate in specific tissue environments. In skin, breast tissue, axillary lymph nodes, and bowel submucosa MC tend to have scroll-poor granules and stain for avidin, chymase, tryptase, and carboxypeptidase, whereas, in lung and bowel mucosa MC granules tend to be scroll-rich and stain only for tryptase with currently available reagents.

Breast↗

PubMed1990

Corpora cavernosa ultrastructure in vascular erectile dysfunction.

Open biopsy of the corpus cavernosum was performed in 13 nondiabetic patients with erectile dysfunction. The history and physical examination, sleep rigidity and tumescence monitoring, hormonal assays, duplex ultrasonography with papaverine, and cavernosometry and cavernosography, formed the basis of categorizing each patient into 1 of 5 etiological groups. These groups included neurogenic, moderate arterial, severe arterial, venous and fibrotic causes for organic erectile dysfunction. The cavernous smooth muscle and endothelium in each patient appeared to be normal on light and electron microscopy. We conclude that cavernous biopsy is of limited value to determine therapeutic options in patients with erectile dysfunction.

Biopsy↗

PubMed1990

Nucleolar organizer regions (NOR) in hyperplastic and neoplastic prostate disease.

Nucleolar organizer regions (NOR) are DNA loops encoding ribosomal RNA production. Detectable by the argyrophilia (AgNOR) of associated proteins, AgNOR numbers correlate with growth fraction and may have diagnostic and prognostic utility in human tumors. Because nucleolar size is important in the diagnosis of prostate carcinoma, we compared AgNOR counts in benign, atypical, and malignant prostate lesions and correlated them with nucleolar diameter. We counted AgNOR in benign prostatic hyperplasia, atypical adenomatous hyperplasia, intraductal dysplasias, and carcinomas of various Gleason grades. The mean AgNOR count per nucleus for benign prostatic hyperplasia nuclei was 4.51; for atypical adenomatous hyperplasia, 5.64; for intraductal dysplasias, 7.35; for carcinoma of Gleason grades 2 + 3, 8.87; and for carcinoma Gleason grades 4 + 5, 10.42. Counts in the carcinomas and intraductal dysplasias were significantly different from those of benign prostatic hyperplasia. Mean AgNOR counts of the carcinomas and intraductal dysplasias did not overlap with those of benign prostatic hyperplasia, suggesting that intraductal dysplasia shares more with carcinoma than benign prostatic hyperplasia. Nucleolar diameters increased from benign prostatic hyperplasia to atypical adenomatous hyperplasia, intraductal dysplasias, and the carcinomas, correlating with increasing AgNOR counts. Nucleolar diameters in the carcinomas were significantly different than those of benign prostatic hyperplasia; those in intraductal dysplasias were not. Our findings suggest that AgNOR counts are superior to nucleolar diameters alone in separating intraductal dysplasias from benign prostatic hyperplasia but provide no additional information in diagnosing carcinoma.

Cell Nucleus↗