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Biomedical subjects

A M Gown

Publications and source records attributed to A M Gown.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of chemoresistance markers in women with epithelial ovarian carcinoma.

OBJECTIVE: Preliminary studies have suggested that lung resistance protein (LRP), multidrug resistance protein (MRP), and p27 may be useful markers of chemoresistance. Our goal was to evaluate the expression of LRP, MRP, and p27 in normal ovaries and chemosensitive and chemoresistant ovarian carcinomas. METHODS: Fourteen women with normal ovaries and fifty women with epithelial ovarian carcinoma who underwent cytoreductive surgery from 1996 through 1998 had specimens stained with immunocytochemistry for LRP, MRP, and p27. All women received paclitaxel/platinum-based chemotherapy. Twenty-nine women had a disease-free survival (DFS) of at least 12 months after completion of chemotherapy (sensitive) and 21 women had persistent disease during treatment (resistant). RESULTS: Evaluation of LRP expression revealed significant differences between the normal ovaries and cancers in both the epithelial (57% vs 90%, P = 0.03) and stromal (86% vs 32%, P = 0.001) components. Evaluation of MRP expression revealed significant differences between normal ovaries and cancers in the epithelial component (7% vs 66%, P = 0.001) but not in the stromal component (14% vs 4%, P = 0.1). Evaluation of p27 revealed significant reductions in expression in cancers compared with normal ovaries for both the epithelial (90% vs 55%, P = 0.02) and stromal (88% vs 5%, P = 0.001) components. Comparison between the chemosensitive and chemoresistant groups revealed no significant differences in expression of LRP and MRP, in either the epithelial or stromal component, but significantly lower levels of p27 were expressed in the epithelial component of the chemoresistant group (P = 0.01). CONCLUSIONS: The expression of LRP, MRP, and p27 is significantly different in ovarian cancers compared with normal ovaries. Low levels of p27 expression are associated with chemoresistance; however, LRP and MRP expression are not prognostic for chemosensitivity.

ATP-Binding Cassette Transporters↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum.

BACKGROUND: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. OBJECTIVE: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). DESIGN: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. RESULTS: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. CONCLUSION: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.

Actins↗
PubMed2001

Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and primary Sjögren's syndrome: case series.

OBJECTIVE: Rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS) are associated with an increased risk of lymphoma. Epstein-Barr virus (EBV), a ubiquitous herpes virus, has been linked etiologically to lymphoma in patients with RA and primary SS. Recently, methotrexate (MTX) has also been linked to the development of these lymphomas. We investigated the frequency of EBV in lymphoma tissue of patients with RA and primary SS and the association of MTX with lymphomagenesis. METHODS: Twenty-three patients with RA and 9 with primary SS with a history of lymphoma were identified by writing to all Arthritis Foundation member rheumatologists in Washington State. Formalin fixed, paraffin embedded tissue blocks were then requested from pathology laboratories. Lymph nodes from 5 RA patients without lymphoma were also studied. In situ hybridization using a biotinylated EBER-1 oligonucleotide probe was used to detect EBV in tissue sections. Positive and negative laboratory controls were used to ensure procedural integrity. RESULTS: Specimens from 21 RA patients were obtained, with 2 subsequently excluded due to specimen quality. Specimens from 6 patients with primary SS were obtained. In situ hybridization for EBV was positive in 5/19 (26%) RA patients and 1/6 patients with primary SS. In the nonmalignant lymph nodes no patient showed EBV. One primary SS and 12 RA patients were known to be taking MTX at the time of lymphoma diagnosis. Of the EBV positive RA lymphoma patients, 4/5 were receiving MTX at the time of diagnosis. These results show that EBV is present in lymphoma tissue of some patients with RA and very few with primary SS. CONCLUSION: EBV is over-represented in the lymphomas of patients with RA, but whether MTX plays a role in predisposing patients with RA and primary SS to the development of lymphoma, perhaps by influencing behavior of EBV, remains unclear.

Adult↗
PubMed2000

Alterations in SPARC and VEGF immunoreactivity in epithelial ovarian cancer.

OBJECTIVE: Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular protein that modulates cell adhesion and growth. It is thought to play a decisive role in tissue remodeling and angiogenesis. Alterations in SPARC expression have been observed in a variety of solid tumors; however, no consistent pattern of deregulation has been characterized. Vascular endothelial growth factor (VEGF) has emerged as an important regulator of tumor neovascularization. Recent work has shown that SPARC modulates the mitogenic activity of VEGF in normal endothelium. While its role in malignant transformation remains elusive, SPARC may contribute to tumor propagation and invasion. This study examines the immunoreactivity of SPARC and VEGF associated with neoplastic transformation of the ovary. METHODS: Immunostaining for VEGF and SPARC protein was performed on 62 archival specimens. RESULTS: Fourteen normal ovaries and 48 ovarian carcinomas were evaluated. SPARC was detected in the stroma of 63% of ovarian carcinomas. In contrast, SPARC was observed in the stroma of only 29% of normal ovaries (P = 0.02). Furthermore, SPARC was limited in normal ovaries to premenopausal patients, juxtaposed either with vesiculated follicles or within the corpus luteum. VEGF was observed in 42% of ovarian carcinomas with immunoreactivity confined to tumor cells. The level of VEGF immunoreactivity was significantly higher in ovarian carcinoma compared to normal ovary epithelium (42 vs 7%, P = 0.02). CONCLUSIONS: Immunoreactivity of SPARC and VEGF is heightened in association with ovarian carcinoma, with a distinct distribution of SPARC in the stroma of neoplastic ovaries and VEGF within tumor cells. No obvious pattern of coincident SPARC and VEGF immunoreactivity was detected. These results indicate the possibility of an aberration in the interaction that has been described in normal endothelium between SPARC and VEGF in association with malignant transformation.

Adult↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Salivary gland basal cell and canalicular adenomas: immunohistochemical demonstration of myoepithelial cell participation and morphogenetic considerations.

OBJECTIVE: To evaluate cellular composition of salivary gland adenomas using 3 monoclonal antibodies that recognize a smooth muscle phenotype confirmed to be sensitive for myoepithelial differentiation. DESIGN: Immunohistochemical evaluation of 25 salivary gland basal cell and canalicular adenomas. SETTING: Archival pathology material from the files of Henry Ford Hospital, Detroit, Mich, and the University of California at San Francisco. RESULTS: All basal cell adenoma variants exhibit some degree of myoepithelial cell participation with periductal, epithelioid, and spindled (stromal-like) morphologic structures. Only the canalicular adenomas, even if mixed with trabecular and solid patterns, are devoid of staining with these 3 antibodies, suggesting an adenoma composed exclusively of ductal luminal cells. CONCLUSIONS: There is an overlapping histomorphologic and common cellular composition of the basal cell adenoma variants with other recognized adenomas, such as pleomorphic adenoma and myoepithelioma. Relative differentiation toward 3 cell phenotypes (ductal luminal, basal, and myoepithelial) and the character of extracellular matrix production in varying proportions by the neoplastic myoepithelial cells distinguishes the spectrum of salivary gland adenomas identified in current classification schemes.

Actins↗
PubMed1999

Monitoring gene expression profile changes in ovarian carcinomas using cDNA microarray.

The development of cancer is the result of a series of molecular changes occurring in the cell. These events lead to changes in the expression level of numerous genes that result in different phenotypic characteristics of tumors. In this report we describe the assembly and utilization of a 5766 member cDNA microarray to study the differences in gene expression between normal and neoplastic human ovarian tissues. Several genes that may have biological relevance in the process of ovarian carcinogenesis have been identified through this approach. Analyzing the results of microarray hybridizations may provides new leads for tumor diagnosis and intervention.

Cloning, Molecular↗