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Biomedical subjects

H Yaziji

Publications and source records attributed to H Yaziji.

27 records · Page 2Linked to original sources

Comparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of HER-2/neu in breast cancer.

PURPOSE: To compare fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in the determination of HER-2/neu status of breast cancers. MATERIALS AND METHODS: FISH and IHC for HER-2/neu were performed on formalin-fixed paraffin sections of 100 consecutive invasive breast cancers. FISH was performed at Beth Israel Deaconess Medical Center, Boston, MA, using the Oncor/Ventana INFORM kit (Ventana Medical Systems, Tucson, AZ; formerly sold by Oncor, Inc, Gaithersburg, MD) in a laboratory certified as proficient in this procedure. IHC was performed at PhenoPath Laboratories, Seattle, WA, using a polyclonal antibody to the HER-2/neu protein. FISH and IHC were analyzed in a blinded fashion, and the results were then compared. Procedure and interpretation times and reagent costs for FISH and IHC were also compared. RESULTS: HER-2/neu was amplified by FISH in 26% of cases, and 23% were HER-2/neu-positive by IHC. FISH and IHC were both assessable in 90 cases. Concordance between FISH and IHC results was seen in 82 of these cases (91%, P <.001). The FISH procedure required more technologist time and more interpretation time per case for the pathologist than IHC. Reagent costs were substantially higher for FISH than for IHC. CONCLUSION: There is a high level of correlation between FISH and IHC in the evaluation of HER-2/neu status of breast cancers using formalin-fixed paraffin-embedded specimens. Although the choice of which assay to use should be left for individual laboratories to make based on technical and economic considerations, our results may make it difficult to justify the routine use of FISH for determination of HER-2/neu status in breast cancer.

Adult↗

Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration-approved scoring system.

PURPOSE: To evaluate the specificity of the HercepTest for Immunoenzymatic Staining (Dako Corp, Carpinteria, CA) for determining HER-2/neu protein expression in breast cancer. MATERIALS AND METHODS: Forty-eight invasive breast cancers previously found to be HER-2/neu-negative by two different immunohistochemical (IHC) assays and not amplified for the HER-2/neu gene by fluorescence in situ hybridization were studied using the HercepTest kit. HercepTest was performed according to the manufacturer's guidelines, and the results were scored on a 0 to 3+ scale using the United States Food and Drug Administration (FDA)-approved grading system. In this system, cases scored as 2+ or 3+ are considered HER-2/neu-positive. RESULTS: Among these 48 cases, the IHC score using the FDA-approved scoring system was 0 in four cases (8.3%), 1+ in 16 (33.3%), 2+ in 21 (43.8%), and 3+ in seven (14.6%). Therefore, 58.4% of these cases were categorized as HER-2/neu-positive, and the specificity of the HercepTest kit for HER-2/neu expression was 41.6%. However, with the use of a modified scoring system that took into account the level of staining of nonneoplastic epithelium, the specificity increased to 93.2%. CONCLUSION: Our results indicate that the HercepTest kit, when used in accordance with the manufacturer's guidelines and the FDA-approved scoring system, results in a large proportion of breast cancers being categorized as positive for HER-2/neu protein expression and that many of these seem to be false-positives. Consideration of the level of staining of nonneoplastic epithelium resulted in improved specificity. The current FDA-approved scoring system for HercepTest results should be reevaluated before its widespread use in clinical practice.

Adult↗

Destructive tophaceous calcium hydroxyapatite tumor of the infratemporal fossa. Case report and review of the literature.

Tophaceous pseudogout is one of the rarest forms of crystal deposition disease, typically presenting as a destructive and invasive mass involving the temporomandibular joint or the infratemporal fossa region in the absence of any other articular manifestations. Previous cases have been assumed to be caused by calcium pyrophosphate dihydrate (CPPD) crystal deposition, based on finding weakly birefringent crystals in the involved tissues. The authors present the unique case of a 65-year-old woman with a destructive and invasive facial mass extending to the middle cranial fossa with microscopic and clinical features consistent with tophaceous pseudogout. High-resolution x-ray crystallographic powder diffraction and Fourier transformed infrared spectroscopy subsequently revealed that the crystals were composed of calcium hydroxyapatite without CPPD. The patient was later found to have primary hyperparathyroidism and mild hypercalcemia. This case demonstrates that tissue deposits of calcium hydroxyapatite can cause a destructive and invasive mass containing weakly birefringent crystals and raises the question of whether previous cases attributed to tophaceous pseudogout resulting from CPPD actually were composed of birefringent calcium hydroxyapatite.

Aged↗

Hemostasis of punctured blood vessels using high-intensity focused ultrasound.

The hemorrhagic complications of vascular injury can be significant. We report on the use of high-intensity focused ultrasound (HIFU) to stop the hemorrhage of punctured blood vessels in pigs. Two HIFU transducers with frequencies of 3.5 and 2.0 MHz, each equipped with a water-filled conical housing, were used. Major blood vessels (femoral artery and vein, axillary artery, carotid artery and jugular vein), 2-10 mm in diameter, of anesthetized pigs were exposed surgically and punctured with 14- and 18-gauge needles to produce moderate to profuse bleeding. Complete hemostasis was achieved in less than 3 min of HIFU treatment in most blood vessels, and all vessels were patent after the treatment. Both HIFU frequencies were effective in producing hemostasis. Gross examination of the HIFU-treated vessels showed a consistent hardening of the soft tissue surrounding the blood vessels, providing a seal for the puncture hole. Microscopic examination of the vessels showed a remarkably localized HIFU treatment, resulting in coagulation of the adventitia, and an extensive fibrin network around the vessels and in the puncture hole. The vessel walls exhibited focal swelling, without evidence of irreversible injury. HIFU may provide a useful method for achieving hemostasis of punctured and traumatized blood vessels in a variety of clinical settings.

Animals↗

Gestational herpes simplex virus hepatitis.

Hepatitis due to herpes simplex virus (HSV) is unusual in healthy individuals. To date, only 56 cases of HSV hepatitis in adult patients have been reported, including 21 pregnant patients. We describe a 25-year-old white woman in her 30th week of gestation who had progressive acute hepatitis. Histologic examination of the liver biopsy specimen showed diffuse microabscesses involving more than 50% of the hepatic parenchyma, with multiple hepatocytes containing Cowdry type A and ground-glass nuclear inclusions. The diagnosis of herpes hepatitis was confirmed by positive immunoreactivity to HSV antibodies in the tissue sections. Intravenous acyclovir therapy was immediately initiated, and the patient's condition improved dramatically. She then had a normal baby at term. Subsequently, the patient had a second pregnancy and an uncomplicated vaginal delivery without recurrence of the disease. Even though alterations of the humoral and cell-mediated immunity occur during pregnancy, herpes hepatitis is rare in pregnant women. Since the prompt administration of antiviral drugs is a lifesaving measure, we recommend including HSV hepatitis in the differential diagnosis of acute hepatitis in pregnancy.

Acute Disease↗

Localization of tartrate-resistant acid phosphatase in human placenta.

Tartrate-resistant acid phosphatase is an inducible marker of cell differentiation and activation expressed by specialized cells of macrophage lineage and some activated lymphocytes. Clinically, this phosphatase is a diagnostic marker for hairy cell leukaemia and osteoclast activity. The cDNA for this enzyme has been cloned from a placental expression library, yet the cell(s) expressing the enzyme protein has not been determined with certainty. Our laboratories have developed a monoclonal antibody, 9C5, suitable for immunohistochemical localization of tartrate-resistant acid phosphatase in paraffin sections. The purpose of this study was to use antibody 9C5 to identify cells expressing tartrate-resistant acid phosphatase in sections of paraffin-embedded, normal, full-term placenta and to determine if those cells expressed other macrophage markers including CD68 (PG-M1 antibody), LN5, lysozyme, alpha 1-antitrypsin and alpha 1-antichymotrypsin. Histochemical localization of activity in frozen sections was compared with immunohistochemical localization in paraffin sections of the same tissue specimens. The activity and antigenicity of this enzyme were detected in decidual cells, syncytiotrophoblast, and some macrophages distributed throughout maternal and embryonic tissues, but not in neutrophils. Unlike other tissues previously examined, placenta contains significant numbers of the phosphate-positive cells that are not of macrophage origin.

Acid Phosphatase↗

Role of p53 immunohistochemistry in differentiating reactive gliosis from malignant astrocytic lesions.

P53 immunohistochemistry has been used to distinguish between malignant tumors and morphologically similar benign processes. In the central nervous system, a major diagnostic dilemma is caused by overlapping features of benign reactive astrocytic lesions and low-grade astrocytomas, especially with small biopsies. P53 immunoreactivity in astrocytes could be useful in differentiating benign reactive lesions from malignant astrocytomas. An immunohistochemical study on 110 brain lesions from 108 patients using a monoclonal antibody (DO-7) against p53 protein was conducted. Using the modified Ringertz and World Health Organization system, the specimens included 22 astrocytomas, 12 anaplastic astrocytomas, 42 glioblastoma multiforme tumors, three nonglial tumors, and 56 reactive astrocytic lesions to 25 neoplasms, nine infectious processes, six cerebrovascular disorders,one metabolic disorder, two vascular malformations, eleven degenerative/demyelinating lesions, and two unknown primary lesions. Immunoreactive astrocytic tumors included 12 (54%) astrocytomas, nine (75%) anaplastic astrocytomas, and 38 glioblastoma multiforme tumors (90%). Among the reactive astrocytic lesions, only five (9%) cases of progressive multifocal leukoencephalopathy were immunoreactive. These data demonstrate that p53 immunoreactivity in astrogliosis is unusual but is to be expected in astrocytomas and can help to differentiate reactive from neoplastic astrocytic lesions.

Adolescent↗

Primary small cell undifferentiated carcinoma of the rectum associated with ulcerative colitis.

Primary small cell undifferentiated carcinomas (SCUCs) are unusual tumors of the colon and rectum. Histologically, these lesions represent a spectrum of neuroendocrine differentiation, with oat cell carcinoma being the most primitive subtype and carcinoid tumors being the most differentiated. This observation is supported by immunohistochemical and ultrastructural findings. We report a case of SCUC of the rectum in a patient with ulcerative colitis. To date, there have been only two reported cases of primary SCUC associated with ulcerative colitis. Recent theories of tumorigenesis attribute most colorectal cancers to a single, pluripotential mucosal stem cell, regardless of the tumor's histologic type.

Carcinoma, Neuroendocrine↗

Immunohistochemical detection of tartrate-resistant acid phosphatase in non-hematopoietic human tissues.

Immunohistochemical studies were done on formalin-fixed, paraffin-embedded tissues to evaluate the specificity of a newly developed monoclonal antibody (9C5) against tartrate-resistant acid phosphatase. Sections from 195 specimens were examined, which included 33 types of tissues/organs. These tissues included normal, inflammatory, and neoplastic processes. Neoplastic tissues from 14 patients with hairy cell leukemia served as positive controls. Epitope enhancement was accomplished either by microwave irradiation in citrate buffer or by boiling in water followed by trypsin digestion. Tissues were reacted with monoclonal antibody 9C5 and stained with either the avidin-biotin peroxidase method or the alkaline phosphatase anti-alkaline phosphatase method. The hairy cells of all cases of hairy cell leukemia reacted positively with 9C5. Other positively stained cells included osteoclasts, activated macrophages and giant cells. Immunohistochemical studies with 9C5, when interpreted within the context of the specificity of this antibody, are useful for the diagnosis and assessment of treatment results for hairy cell leukemia. Monoclonal antibody 9C5 also may be useful as a marker for osteoclasts and the activated macrophages and for the diagnosis of disorders involved by these cells.

Acid Phosphatase↗