PubMed Health⌕ Search

Biomedical subjects

H Yaziji

Publications and source records attributed to H Yaziji.

At least 19 recordsLinked to original sources

Immunohistochemical analysis of gynecologic tumors.

Ancillary techniques such as immunohistochemistry (IHC) enable the surgical pathologist to extract additional information from fixed, deparaffinized tissue specimens and to provide data critical to optimal clinical management of the patient. In this review of applications of IHC to the analysis of gynecologic malignancies, the usefulness of immunohistochemical analysis of neoplasms of the cervix, endometrium, and ovary is summarized. In the uterine cervix, dysplasia is associated with qualitative and quantitative alterations in the expression of the Ki-67 antigen expression, as well as an ability to detect human papillomavirus. Endometrial endometrioid adenocarcinomas display a highly characteristic immunophenotype, with coexpression of cytokeratin and vimentin and demonstration of foci of high molecular weight cytokeratin expression; in addition, IHC analysis of estrogen and progesterone receptor and p53 expression can provide important prognostic information about this tumor. Stromal tumors of the endometrium may display a partial smooth muscle immunophenotype, but novel markers such as CD10 provide new tools for the identification of these tumors. The immunophenotypes of the normal ovarian surface epithelium (OSE) and corresponding tumors display significant overlap with, but important distinctions from, mesothelium, and important new markers such as the Wilms tumor gene product can prove useful in the identification of carcinomas of the OSE. Important prognostic markers for carcinomas of the OSE include the HER-2/neu gene product and p53, alterations of which can both be assessed by IHC techniques. Finally, the recent availability of markers of ovarian stroma, including Melan-A and inhibin-alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest protean histological appearances.

Biomarkers, Tumor↗

E-cadherin reactivity of 95 noninvasive ductal and lobular lesions of the breast. Implications for the interpretation of problematic lesions.

Studies suggest that E-cadherin is useful to classify epithelial breast lesions as ductal or lobular, but extensive experience with this antibody is lacking. We studied reactivity of lesions with classic and indeterminate morphologic features. We reviewed 95 lesions and divided them into unanimous and nonunanimous diagnosis groups; the unanimous group served as benchmark lesions to which E-cadherin reactivity could be standardized and compared. All 37 ductal lesions in the unanimous group had strong, diffuse E-cadherin reactivity. Two of 22 classic lobular carcinoma in situ (LCIS) lesions had sparse E-cadherin-reactive lobular cells within a few terminal duct lobular units. Neither displayed transition from nonreactive to reactive cells. Of 36 lesions in the nonunanimous group, 19 had insufficient morphologic features for definitive classification. Only 6 of 19 were E-cadherin reactive, including several minimally proliferative lesions. The other 17 lesions in the nonunanimous group had LCIS and ductal carcinoma in situ (DCIS) features. All had no E-cadherin, or strong membrane reactivity of constituent cells in varying proportions, without a transition between reactive and nonreactive cells. Results suggest that the majority of morphologically nondiagnostic atypical lesions are lobular, including those associated with DCIS. E-cadherin seems to be absent in most lobular lesions.

Benchmarking↗

Author reply

Explore the source record for details and available documents.

Journal Article↗

Primary alveolar soft part sarcoma of the stomach: a case report and review.

Alveolar soft part sarcoma (ASPS) is a rare tumor typically located in skeletal muscles and muscolofascial planes. Isolated cases of ASPS have been described as arising in the viscera. We report a mesenchymal tumor of the stomach in a 54-year-old Italian woman without evidence of primary neoplasm elsewhere ten years following the initial diagnosis. The histologic, histochemical, immunohistochemical, and electron microscopic findings were all consistent with the diagnosis of ASPS and allowed differentiating it from morphologically similar and more common tumors, such as metastatic renal cell carcinoma and paraganglioma. The patient is alive and well ten years following the initial presentation.

Biomarkers, Tumor↗

Detection of stromal invasion in breast cancer: the myoepithelial markers.

Breast cancer can only be life threatening when it becomes invasive, at which point it carries potential for spreading and metastasis. Therefore, it is critical to distinguish invasive carcinomas (IC) from noninvasive lesions, the latter including ductal carcinoma in situ (DCIS) and benign breast lesions. While this distinction is usually made based on histologic evaluation alone, in a small but significant number of cases, accurate diagnosis may be impossible, particularly in the context of core needle biopsies. To this end, a number of immunohistochemical markers have been utilized to help establish the presence (or absence) of stromal invasion. The fact that the loss of the myoepithelial cell (MEC) layer is a hallmark of IC (but not DCIS) suggests the use of antibodies to MEC to distinguish IC from DCIS. However, these markers have a wide range of specificity and sensitivity, with the potential for problems in interpretation. The use of many of these markers is limited by high rates of 'false positive' or 'false negative' immunostaining. In this review, the biology of stromal invasion in breast carcinomas will be discussed, as well as the various myoepithelial markers, with emphasis on pitfalls related to their sensitivity and specificity in the detection of MECs in the breast. Finally, the authors will discuss diagnostically challenging breast lesions, which may require the use of MEC marker studies to reach a definitive diagnosis.

Biomarkers↗

HER-2/neu protein expression in breast cancer evaluated by immunohistochemistry. A study of interlaboratory agreement.

Immunohistochemistry (IHC) is used commonly for evaluating HER-2/neu protein expression in breast cancer. Given the potential clinical importance of HER-2/neu status in patient management, interlaboratory variability in HER-2/neu IHC results in a matter of legitimate concern. We compared the results from 2 laboratories for HER-2/neu determined by IHC on paraffin sections of the same 100 consecutive invasive breast cancers. Both laboratories used the same primary antibody; however, different methods for heat-induced epitope retrieval (microwave or steam) and immunostaining (automated equipment from different manufacturers) and different scoring systems (positive-negative and 0-4+) were used. Slides were read in a blinded fashion and the results from the 2 laboratories were compared. Of the 93 cases evaluable in both laboratories, 24% were scored as HER-2/neu-positive at 1 laboratory, and 23% were scored as positive at the other. Complete concordance in categorization of HER-2/neu status between the 2 laboratories was achieved in 90 of 93 cases. Excellent interlaboratory agreement for HER-2/neu IHC was attained using the same primary antibody to HER-2/neu, even without standardization of assay method or scoring criteria. However, standardization of these parameters remains an important objective to optimize interlaboratory agreement.

Adult↗

Cytokeratin 8 immunostaining pattern and E-cadherin expression distinguish lobular from ductal breast carcinoma.

Immunohistochemistry using antibodies to cytokeratin 8 can serve as a valuable diagnostic tool for the differentiation of lobular from ductal carcinomas of the breast. In contrast with ductal carcinomas, which exhibit a peripheral-predominant immunostaining pattern, adjacent tumor cells "molding" to each other, lobular carcinomas exhibit a ring-like perinuclear immunostaining pattern, creating a "bag of marbles" appearance with neighboring tumor cells. This immunostaining pattern is stable even in the tumors that otherwise do not exhibit characteristic histomorphologic features (i.e., solid or pleomorphic type of a lobular carcinoma) and tumors that mimic growth patterns characteristic of the respective other tumor type (i.e., targetoid or single-file growth pattern in a ductal carcinoma). Furthermore, we demonstrate that ductal carcinomas express E-cadherin in a similar peripheral-predominant immunostaining pattern (33/33 cases), while all 15 lobular carcinomas were negative for E-cadherin, suggesting a role for E-cadherin in the architectural organization of the cytoskeletal scaffolding within the tumor cells.

Breast Neoplasms↗

Use of high-intensity focused ultrasound to control bleeding.

OBJECTIVE: High-intensity focused ultrasound (HIFU) has been shown to be effective in controlling hemorrhage from punctures in blood vessels. The objective of the current study was to investigate the capability of HIFU to stop bleeding after a more severe type of vascular injury, namely longitudinal incisions of arteries and veins. METHODS: The superficial femoral arteries, common femoral arteries, carotid arteries, and jugular veins of four anesthetized pigs were exposed surgically. A longitudinal incision, 2 to 8 mm in length, was produced in the vessel. HIFU treatment was applied within 5 seconds of the onset of the bleeding. The HIFU probe consisted of a high-power, 3.5-MHz, piezoelectric transducer with an ellipsoidal focal spot that was 1 mm in cross section and 9 mm in axial dimension. The entire incision area was scanned with the HIFU beam at a rate of 15 to 25 times/second and a linear displacement of 5 to 10 mm. A total of 76 incisions and HIFU treatments were performed. RESULTS: Control of bleeding (major hemosatsis) was achieved in all 76 treatments, with complete hemostasis achieved in 69 treatments (91%). The average treatment times of major and complete hemostasis were 17 and 25 seconds, respectively. After the treatment, 74% of the vessels in which complete hemostasis was achieved were patent with distal blood flow and 26% were occluded. The HIFU-treated vessels showed a consistent coagulation of the adventitia surrounding the vessels, with a remarkably localized injury to the vessel wall. Extensive fibrin deposition at the treatment site was observed. CONCLUSION: HIFU may provide a useful method of achieving hemostasis for arteries and veins in a variety of clinical applications.

Animals↗

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↗