PubMed Health⌕ Search

Biomedical subjects

E A Montgomery

Publications and source records attributed to E A Montgomery.

At least 19 recordsLinked to original sources
PubMed2001

Frequent beta-catenin mutations in juvenile nasopharyngeal angiofibromas.

Juvenile nasopharyngeal angiofibromas (JNAs) are locally aggressive vascular tumors occurring predominantly in adolescent males. The pathogenesis of JNAs is unknown. Recently, JNAs have been reported to occur at increased frequency among patients with familial adenomatous polyposis, suggesting that alterations of the adenomatous polyposis coli (APC)/beta-catenin pathway might also be involved in the pathogenesis of sporadic JNAs. We analyzed somatic beta-catenin and APC gene mutations in 16 sporadic JNAs from nonfamilial adenomatous polyposis patients using immunohistochemistry for beta-catenin, and direct DNA sequencing for exon 3 of the beta-catenin gene and the mutation cluster region of the APC gene. Nuclear accumulation of beta-catenin was diffusely present in the stromal cells but not in the endothelial cells of all 16 JNAs. Activating beta-catenin gene mutations were present in 75% (12 of 16) of JNAs. Six JNA patients also had recurrent tumors after surgery, and in all cases the beta-catenin gene status of the recurrent JNA was identical to the initial tumor. No mutations in the mutation cluster region of the APC gene were detected in the four JNAs without beta-catenin mutations. The high frequency of beta-catenin mutations in sporadic JNAs and the presence of identical beta-catenin gene mutations in recurrent tumors indicates that activating beta-catenin gene mutations are important in the pathogenesis of JNAs. The immunohistochemical localization of beta-catenin only to the nuclei of stromal cells further suggests that the stromal cells, rather than endothelial cells, are the neoplastic cells of JNAs.

Adolescent↗
PubMed2001

Counting alleles reveals a connection between chromosome 18q loss and vascular invasion.

The analysis of loss of heterozygosity (LOH) is perhaps the most widely used technique in cancer genetics. In primary tumors, however, the analysis of LOH is fraught with technical problems that have limited its reproducibility and interpretation. In particular, tumors are mixtures of neoplastic and nonneoplastic cells, and the DNA from the nonneoplastic cells can mask LOH. We here describe a new experimental approach, involving two components, to overcome these problems. First, a form of digital PCR was employed to directly count, one by one, the number of each of the two alleles in tumor samples. Second, Bayesian-type likelihood methods were used to measure the strength of the evidence for the allele distribution being different from normal. This approach imparts a rigorous statistical basis to LOH analyses, and should be able to provide more reliable information than heretofore possible in LOH studies of diverse tumor types.

Alleles↗
PubMed2001

Pleomorphic liposarcoma: a clinicopathologic analysis of 19 cases.

Pleomorphic liposarcoma is a variant of liposarcoma defined morphologically by the presence of pleomorphic lipoblasts. Because of its rarity, there are limited studies with long-term follow-up information. Nineteen pleomorphic liposarcomas were studied. Unequivocal pleomorphic lipoblasts were required for inclusion. In each case, the following features were noted: tumor site; tumor size; tumor depth; predominant histologic pattern (epithelioid or malignant fibrous histiocytoma [MFH]-like); extent of necrosis (absent, less than 15%, or at least 15%); mitotic counts; treatment and clinical follow-up. Patients were 11 females and 8 males, aged 33-87 years (mean, 64.5 y; median, 70 y). Tumors involved the extremities (13 patients: intramuscular in 10, subcutaneous in 2, depth unknown in 1), retroperitoneum (4 patients), mediastinum (1 patient), and paratesticular region (1 patient). Size ranged from 4.5--31 cm (mean, 11.9 cm; median, 12.0 cm). Predominant pattern was epithelioid in 7 and MFH-like in 12. Necrosis was present in 15 (79%) and was extensive (36 15%) in 14 patients. Mitotic counts ranged from 0.2--3.4/10 high-power fields (mean, 1.4; median, 1.4) by the average-count method and from 1--6/10 high power fields by the highest count method (mean, 2.9; median, 3.0). All patients were treated surgically; 10 patients received adjuvant chemotherapy and/or radiation therapy. On follow-up of 18 patients (range, 2--129 mo; mean, 35.4 mo; median, 23 mo) nine (50%) were dead of disease (range, 2--48 mo; mean, 20.1 mo; median, 12 mo), one died of other causes 2 months after diagnosis, two were alive with disease, five were disease free, and one was alive at 129 months (tumor status unknown). Five had recurrences (range, 3--28 mo; mean, 14.4 mo; median, 8 mo), and four of five (80%) with recurrences were dead of disease. Metastases developed in eight patients (range, 4--48 mo; mean, 19.5 mo; median, 11.5 mo), most commonly to the lungs. In conclusion, pleomorphic liposarcoma is a rare tumor of adulthood that occurs most commonly in the deep, soft tissues of the extremities. It behaves as a high-grade sarcoma that frequently metastasizes, most commonly to the lungs. Although this tumor has a wide range of histologic appearances, no clinical or pathologic feature is predictive of a more aggressive clinical course.

Adult↗
PubMed2000

Endoscopic mapping and surrogate markers for better surveillance in Barrett esophagus. A study of 700 biopsy specimens.

Surveillance methods in Barrett esophagus (BE) using light microscopic examination of random biopsy specimens may miss focal dysplasia. In addition, dysplastic foci identified initially may not be relocated subsequently, making chemoprevention studies difficult. By using a special gastroscope, systematic mapping (4-quadrant biopsy specimens at 1-cm intervals) was performed in 22 patients (33 total mappings yielding 700 biopsy specimens). H&E, immunohistochemistry, and DNA ploidy analysis were performed. c-erbB-2 and positive Ki-67 were detected only in dysplastic sites; thus, their detection did not precede morphologically identifiable dysplasia. On the other hand, aneuploidy and p53 were detected in dysplastic and nondysplastic areas. p53 was correlated with dysplasia, and S-phase narrowly missed correlation, while aneuploidy was not correlated. PCNA and bcl-2 were ubiquitous, limiting their usefulness. On second maps, epithelial type was reidentified with 81% accuracy. A significant correlation was found between p53 and dysplasia. Sites of dysplasia and abnormal biomarkers could be relocated accurately by using endoscopic mapping. Therefore, mapping combined with biomarker studies may provide better surveillance and serve as a useful technique in chemoprevention studies.

Adult↗
PubMed2000

What are the CD34+ cells in benign peripheral nerve sheath tumors? Double immunostaining study of CD34 and S-100 protein.

To determine whether CD34 expression in nerve sheath lesions was found in a unique cell population or in a subset of nerve sheath cells, we performed double immunohistochemical staining using a standard avidinbiotin complex method with 2 separate color developing systems. We studied 40 neurofibromas and 16 neurilemomas. All lesions strongly expressed S-100 in nuclei and cytoplasm. CD34 was detected in cells having ameboid dendritic cytoplasm present in greatest numbers in Antoni B zones of neurilemomas, myxoid zones of neurofibromas, at the periphery of lobules in both tumor types, and condensed in apposition to perineurium. The CD34+ cells also were detected in normal nerves. They were infrequent in Antoni A zones of neurilemomas. No dual S-100 and CD34 expression was seen. This double immunostaining confirms the presence of a CD34-reactive non-Schwannian cell type in these neural neoplasms. As the CD34+, S-100-negative cell population is present also in normal nerves and infrequently seen in the areas of cellular neoplastic Schwann cells, CD34+, S-100-negative cells in peripheral nerve sheath tumors most likely are nonneoplastic and may have a supportive function.

Adolescent↗
PubMed1999

Qualitative mapping of Barrett's metaplasia: a prerequisite for intervention trials.

BACKGROUND: Barrett's esophagus may present as a cellular mosaic with irregular longitudinal extensions of intestinal epithelium, spotty areas of dysplasia and other intermediate markers for cancer risk. It may not be possible to detect and reproducibly localize these findings with routine endoscopic biopsies. A more systematic biopsy protocol is necessary for chemopreventive studies to be feasible. METHODS: Utilizing an adapted upper endoscope that allows accurate evaluation of distance from the incisors and rotatory position, chromoendoscopy with toluidine blue and systematic mapping (4 quadrant jumbo biopsies at 1 cm intervals) were performed twice on 18 patients with Barrett's esophagus (second procedure 1 to 3 months after baseline study). All biopsy specimens were subjected to routine and immunohistochemical staining and flow cytometry to create baseline and follow-up maps for each patient. Eight of the 18 patients also underwent standard surveillance biopsies within 6 months of the systematic mapping procedures. RESULTS: Epithelium type was reproducibly identified with 94% accuracy on second endoscopic maps. Ploidy, p53, and Ki-67 status were also reproducibly identified on second endoscopic maps (97%, 89%, and 85%, respectively). Dysplasia was found in 7 of 18 patients at similar sites at each mapping procedure (3 patients with high-grade dysplasia, 4 with low-grade dysplasia). Five of the patients who had dysplasia on mapping had also undergone standard surveillance. Low-grade dysplasia was missed in 2 of 3 patients and 1 patient with high-grade dysplasia had only low-grade dysplasia detected with standard biopsies. CONCLUSIONS: Utilizing a modified gastroscope and this methodology, we reliably located sites of dysplasia and other biomarkers within a field of Barrett's esophagus. Patients had variable areas of dysplasia that were missed on standard endoscopic surveillance.

Adenocarcinoma↗
PubMed1998

Inflammatory myxohyaline tumor of distal extremities with virocyte or Reed-Sternberg-like cells: a distinctive lesion with features simulating inflammatory conditions, Hodgkin's disease, and various sarcomas.

We report 51 cases of a previously undescribed tumor of the distal extremities that is often mistaken for an inflammatory or infectious process, Hodgkin's disease, or various sarcomas. These lesions developed in patients of all ages (range, 4-81 yr; median, 40 yr) and affected the sexes nearly equally (27 men, 24 women). They presented as a painless mass of the fingers (14 cases), hand (11 cases), wrist or arm (10 cases), toe or foot (8 cases), or lower leg (5 cases), usually within the subcutaneous tissues. Grossly, they were infiltrative, multinodular masses characterized by a dense chronic inflammatory infiltrate that merged with a stroma, which varied from densely hyaline to focally myxoid and contained sheets of short spindled to rounded epithelioid cells. Focally, the epithelioid cells were extremely large with bizarre, vesicular nuclei and macronucleoli resembling Reed-Sternberg cells or virocytes. Despite the level of atypia, mitotic activity was low. The tumor cells consistently expressed vimentin but lacked a variety of other mesenchymal, epithelial markers, e.g., S100 protein, desmin, actin, neuron-specific endolase, epithelial membrane antigen, HMB-45, CD34) and leukocyte markers (CD15, CD30, CD45). Keratin was noted focally and weakly in four cases and CD68 focally in six cases, the latter suggesting that the cells had acquired phagocytic properties. Immunostains for cytomegalovirus were negative. Polymerase chain reaction for Epstein-Barr virus showed amplification levels consistent with latent infection in 4 of 10 cases, but no cases showed levels consistent with active infection. All of the bacterial and viral cultures were negative. Follow-up information was available in 27 cases. Recurrences developed in six patients (interval, 15 mo-10 yr), but there were no metastases or tumor-related deaths. In one patient, progressive proximal extension up the arm was noted. Although the most common submitting diagnosis was that of an inflammatory or infectious process, the negative studies for infectious agents, clinical behavior with local recurrences, immunophenotypic profile, and cytologic atypia support the idea that these are unusual mesenchymal neoplasms with at least the potential for local recurrence. It remains to be investigated whether with time these lesions will prove to have metastatic potential.

Adolescent↗
PubMed1997

Solitary fibrous tumors: a series of lesions, some in unusual sites.

Solitary fibrous tumor (SFT) is a rare neoplasm that, in addition to its classic presentation as a pleural-based mass, can also be encountered in unusual sites. The main difficulty in making the diagnosis of SFTs results from the unfamiliarity with its diverse clinical and pathologic features. This series of SFTs, some with unusual clinicopathologic presentation, included nine women and two men, ranging in age from 28 years to 74 years (five in pleura, one in lung parenchyma, one in breast, and four in mediastinum). The tumors were locally excised in eight cases and were resected along with portions of lung parenchyma in three. A panel of immunohistochemical stains was used to characterize these tumors. They were all vimentin-positive and, with the exception of one case, CD34-positive. Tumors were negative with antibodies directed against cytokeratin, factor VIII-related antigen, S-100 protein, muscle-specific actin, and smooth-muscle actin. Various diagnoses were initially rendered for these clinically and pathologically diverse lesions by the examining pathologists. Awareness of the various gross and microscopic patterns of these tumors, the possibility of occurring in unusual sites, and the use of immunohistochemical stains, particularly CD34, should eliminate most of the difficulties in arriving at a correct diagnosis. One patient died of metastatic breast cancer; all other patients were alive and well with a median follow-up of 17 months.

Adult↗
PubMed1996

Chest wall fibromatosis associated with silicone breast implants.

Aggressive fibromatosis is a well described locally destructive benign lesion, comprising 0.3% of all solid tumors. Although the chest wall is a common location, this tumour has rarely been associated with breast tissue or breast implants. Herein is only the fourth case described in conjunction with a breast implant and the only case linked to a ruptured silicone implant. This tumour was locally aggressive and required wide surgical resection, including removal of the chest wall, to gain control. Wide surgical resection is recommended with the application of adjuvant radiation therapy being more controversial.

Adult↗
PubMed1996

High-resolution chromoendoscopy for the diagnosis of diminutive colon polyps: implications for colon cancer screening.

BACKGROUND & AIMS: A visual, nonbiopsy technique that could reliably determine the histology of diminutive colorectal polyps could greatly reduce the cost of colon cancer screening. This study was designed to report our experience using a high-resolution colonoscope combined with indigo carmine dye to diagnosis diminutive colorectal polyps. METHODS: Colonoscopy using a Fujinon EC-400 HM/HL was performed in 36 patients with polyps <10mm in diameter. Polyps from the first 12 patients (phase 1) were sprayed with 10 mL of 0.2% indigo carmine dye, and a biopsy was performed or a specimen removed and submitted for histological analysis. The morphological data were used to predict polyp histology in the subsequent 24 patients (phase 2). RESULTS: Hyperplastic polyps had a characteristic surface "pit pattern" of orderly arranged "dots" that resembled the surrounding, nonpolypoid mucosa. Adenomatous polyps had surface "grooves" or "sulci." Sensitivity and specificity of our techniques in distinguishing adenomatous from nonadenomatous colorectal polyps were 93% and 95% respectively. CONCLUSIONS: High-resolution chromoendoscopy provides morphological detail of diminutive colorectal polyps that correlates well with polyp histology. If incorporated into colon cancer screening, these techniques may limit the need for biopsy and/or subsequent colonoscopy and ultimately decrease costs.

Adult↗
PubMed1996

Barrett esophagus with dysplasia. Flow cytometric DNA analysis of routine, paraffin-embedded mucosal biopsies.

Flow cytometric DNA ploidy analysis has been reported to be more objective and sensitive than morphologic evaluation as a surveillance method in patients with Barrett esophagus (BE) for the development and progression of precancerous lesions. Such analyses are typically performed using fresh samples that require a separate or "jumbo" biopsy, are prone to false DNA aneuploidy if not promptly processed, and do not allow for retrospective studies. The feasibility of performing flow cytometric DNA analysis on paraffin-embedded biopsies was studied to circumvent some of these problems using 12 squamous esophageal mucosa with inflammation and 58 BE cases showing varying degrees of dysplasia. Among the BE cases, 12 had no dysplasia, 20 were indefinite for dysplasia, 14 had low grade dysplasia, and 12 had high grade dysplasia. Satisfactory histograms were obtained in 86% of the analyzed samples. Among cases with adequate histograms, DNA aneuploidy was identified in 77% with high grade dysplasia, 16% with low grade dysplasia, 23% of indefinite for dysplasia, and 0% without dysplasia. One of the esophagitis samples was also DNA aneuploid. Correlation of DNA aneuploidy and degree of dysplasia is highly significant (P = .001). The authors have demonstrated that routinely processed paraffin-embedded biopsies can be used for flow cytometric ploidy analysis. DNA aneuploidy was highly correlated with degree of dysplasia and serves as a quantitative prognostic indicator for prospective as well as retrospective studies of the evolution of BE to carcinoma.

Barrett Esophagus↗
PubMed1996

Immunohistochemical staining for glutathione S-transferase predicts response to platinum-based chemotherapy in head and neck cancer.

The glutathione S-transferases (GSTs) play an important role in the cell's defense against toxic substances. The GSTs are a family of enzymes produced by several genes that interact with distinct but overlapping substrates and that may play a role in resistance of tumor cells to several chemotherapeutic agents. We examined the correlation between expression of GSTs determined by immunohistochemistry and clinical response to platinum-based chemotherapy in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (complete response + partial response) for patients with low GST scores was 88% (21 of 24), whereas among the patients with high GST scores, the overall response rate was 19% (6 of 32; P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 23 patients treated with neoadjuvant chemotherapy, the overall response rate for patients with low GST scores was 100% (14 of 14), whereas among the patients with high GST scores, the overall response rate was 44% (4 of 9; P = 0.002). Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST scores was 70% (7 of 10), whereas among the patients with high GST scores, the overall response rate was 8.6% (2 of 23; P < 0.001). We conclude that GST expression correlates well with response to platinum-based chemotherapy in head and neck cancer.

Antineoplastic Agents↗
PubMed1995

Flow cytometric DNA analysis of ulcerative colitis using paraffin-embedded biopsy specimens: comparison with morphology and DNA analysis of fresh samples.

OBJECTIVES: The detection of aneuploidy in colonic mucosa by flow cytometric DNA analysis has been advocated as an indicator of high risk for ulcerative colitis (UC) patients developing colon carcinoma. To date, studies have primarily utilized fresh tissue and have had two limitations: a significant number of possible false-positive findings (aneuploidy in the absence of detectable dysplasia) that may be due to DNA degradation, and the inherent inability to perform retrospective studies. The latter has compromised the adequate assessment of flow cytometric DNA analysis for its clinical utility in UC patients. Our objective was to attempt to overcome the limitations that have been present in DNA analysis by flow cytometry. METHODS: After having established, in our laboratory, an optimal method that allowed reliable DNA analysis on paraffin-embedded mucosal biopsy specimens, we conducted three separate studies to address the above problems associated with DNA analysis with fresh colonic samples: 1) comparison of DNA analysis between fresh and paraffin-embedded colonic mucosal samples from UC patients without dysplasia, 2) correlation between morphology and DNA ploidy on paraffin-embedded tissues showing no dysplasia and various degrees of dysplasia, and 3) sequential analysis of fresh, normal colonic mucosal samples to further evaluate possible causes of false aneuploidy. RESULTS: We observed 1) that there is discordance in DNA ploidy between paraffin-embedded and fresh samples showing no dysplasia in that aneuploidy was found in 33/46 (72%) of fresh samples, whereas 3/40 (7.5%) were aneuploid by biopsies from the corresponding anatomic sites. 2) There is excellent correlation between dysplasia and DNA ploidy results with paraffin-embedded tissue, i.e., none of 16 samples negative for dysplasia, none of seven samples indefinite for dysplasia, and seven of eight samples positive for dysplasia were aneuploid. 3) DNA degradation produced a spurious, near-diploid aneuploid peak in a normal colonic mucosal sample when it was left in saline more than 1 hr before analysis. CONCLUSIONS: The above-described results demonstrate that performing flow cytometric DNA analysis with formalin-fixed paraffin-embedded biopsy samples is feasible and that this technique may provide more reliable ploidy results than does the use of fresh samples, when rapid refrigeration and/or freezing of the fresh samples cannot be accomplished consistently, and will permit retrospective DNA ploidy studies assessing risk of cancer in UC patients.

Adult↗
PubMed1995

Comparison of nursing home residents admitted from home or hospital.

A growing elderly population coupled with a reduction in hospital long term care has led to an increase in the independent nursing home sector. This is an expensive resource. Proper placement is therefore essential to ensure its efficient use. Prior to the introduction of care management there was no standard assessment procedure for admission to nursing home care from different sources. A nursing home population (n = 624) in North and West Belfast was studied and mental scores, levels of disability, and the source of admission to the nursing home recorded. Residents admitted from geriatric medical units (n = 132) were compared with those from general medical and surgical wards (n = 168) and those from home (n = 243). Residents who were admitted from a geriatric unit were the most disabled, those admitted from home were the least and those from general wards had intermediate levels of disability (p < 0.005). This is likely to be the result of different assessment procedures for prospective nursing home residents. With the introduction of care management, it is hoped that standardised assessment will follow. The roles of different medical specialists in this process is not yet clear. Further study is needed to assess the appropriateness of placement in nursing homes under care management.

Aged↗
PubMed1994

Diffuse hemorrhagic gastroenteropathy: report of a new entity.

An apparently novel entity, diffuse hemorrhagic gastroenteropathy (DHG), in a 70-year-old female who had an unremitting course of chronic gastrointestinal blood loss for 3 years requiring transfusion of more than 200 units of packed red blood cells over this period is reported here. Endoscopy showed diffusely hemorrhagic mucosa in the stomach, duodenum, and small bowel. Full-thickness biopsy of the stomach and small intestine revealed luminal narrowing of capillaries and post-capillary venules within the lamina propria due to swelling and some proliferation of the endothelial cells with margination and emigration by neutrophils as well as partial occlusion of some vessels by fibrin thrombi. DHG may represent a new entity characterized by mucosal hemorrhage due to local mucosal ischemia of the gastrointestinal tract secondary to a small vessel "vasculopathy" apparently restricted to this site.

Aged↗