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Mark H Stoler

Publications and source records attributed to Mark H Stoler.

27 records · Page 2Linked to original sources

TACC3 expression and localization in the murine egg and ovary.

A protein spot cored from a silver-stained two dimensional (2D) gel of germinal vesicle stage immature mouse oocytes was identified as Transforming Acidic Coiled Coil containing protein (TACC3) by tandem mass spectrometry. PCR amplification revealed two alternatively spliced forms, Tacc3a and Tacc3b, in mouse ovarian cDNA libraries. TACC3a encoded a 630 aa protein with a predicted mass of 70 kDa. It contained seven 24 aa repeats at the N-terminus and two coiled-coil domains at the C-terminus. TACC3b encoded a 426 aa protein with a predicted mass of 49 kDa also containing two coiled coil domains, but lacking the 168 aa repeat region. In addition to homology to the TACC family members, murine TACC3 also showed 35.7% identity to the Xenopus protein, Maskin, a cytoplasmic polyadenylation element binding protein (CPEB)-associated factor. Northern blot analysis demonstrated that TACC3a is abundantly expressed in adult testis and spleen and is moderately expressed in the ovary, heart, and lung, suggesting a wide tissue distribution. Both myc-tagged TACC3a and TACC3b targeted to the cytoplasm of transiently transfected CV-1 cells. In situ hybridization of mouse ovarian tissue sections displayed abundant expression of TACC3 specifically in the cytoplasm of growing oocytes, but not in primordial or atretic follicles. This pattern of expression suggests that TACC3 is expressed in ovarian cells undergoing active growth and development.

Alternative Splicing↗

Interobserver interpretative reproducibility of GOLDFISH, a first generation gold-facilitated autometallographic bright field in situ hybridization assay for HER-2/neu amplification in invasive mammary carcinoma.

Clinical laboratory testing for HER-2/neu gene amplification by fluorescence in situ hybridization is not widely used in diagnostic pathology laboratories. A bright field alternative permitting direct visualization of gene amplification using conventional microscopy may be more readily incorporated into routine diagnostic pathology practice. Interobserver reproducibility represents an important component of the validation of such an assay. We tested the hypothesis that a first-generation bright field alternative to fluorescence in situ hybridization, a Nanogold (Nanoprobes, Inc, Yaphank, NY, USA) (or gold-label)/autometallographic assay for HER-2/neu gene amplification in breast carcinoma, can be reproducibly interpreted by pathologists. Reference standard was direct fluorescence in situ hybridization supplemented by RNA/RNA in situ hybridization. Reproducibility of selected conventional histologic parameters was captured based on a hematoxylin and eosin slide accompanying the GOLDFISH preparation (gold-facilitated autometallographic in situ hybridization) as an indication of comparative reproducibility. The average kappa among GOLDFISH observers was 0.84, which was at least or concordant of observers scoring nuclear grade (kappa = 0.50) and the presence of in situ carcinoma (kappa = 0.57) by conventional histopathology. The GOLDFISH assay was specifically designed for qualitative interpretation, thus obviating the need for oil immersion microscopy and signal enumeration, and its interpretation was highly reproducible among five pathologists.

Breast Neoplasms↗

Agarose mold embedding of cultured cells for tissue microarrays.

There are several indications for the placement of samples of cultured cells in tissue microarrays (TMAs). To optimize this technique, three embedding procedures were compared: embedding of fixed cells pelleted by centrifugation, embedding of cells dispersed in an agarose matrix, and embedding of pelleted cells packed into the center of hollow agarose molds. TMAs were made from these preparations. The number of cells per tissue spot and the number of histologic sections that could be obtained from the preparations were determined. The agarose matrix and agarose mold techniques resulted in the longest core samples, while the cell pellet and agarose mold methods resulted in the greatest cell density. Thus, the use of cylindrical agarose molds optimizes both the number of cells present on a histologic section of a TMA, and the number of histologic sections that can be obtained from a TMA. This technique results in a paraffin-embedded cell preparation that yields a cell density of approximately 1000 cells per 0.6-mm diameter circular histologic section, and that produces uniform core samples the full thickness of the donor block. Histologic sections of TMAs prepared in this manner were validated in immunohistochemical and in situ hybridization assays.

Cell Count↗

Expression of cytokeratins 7 and 20 in ovarian neoplasia.

To further delineate specific staining patterns and refine the differential usefulness of cytokeratin (CK) 7/20 staining, we studied multiple ovarian tumors and primary nongynecologic neoplasms likely to metastasize to the ovary. Immunohistochemical analysis with semiquantitative grading to give quartile scores (0-4) was performed on 127 cases. Subsequent analysis indicated that a more informative diagnostic segregation could be achieved with a biphasic grading system (>50% staining, positive; 50% or less, negative). Lower intestinal tumors were CK7- and usually CK20+, while upper gastrointestinal tumors, including those of pancreatobiliary origin, were mostly CK7+ and CK20-. Serous papillary ovarian tumors were all CK7+ and CK20-. Mucinous ovarian carcinomas were all CK7+ and slightly more often CK20-, whereas the small number of ovarian borderline mucinous tumors studied were the most problematic, with no clear pattern. Multiple different tumor types from all nonovarian gynecologic sites were fairly consistently CK7+ and almost always CK20-. Differential CK staining of mucinous tumors of the female genital tract using CK7 and CK20 is useful for predicting the site of origin, provided samples are adequate in size. The most specific usefulness is the identification of lower gastrointestinal vs "other" neoplasms.

Adenocarcinoma, Mucinous↗

"See-and-treat" loop electrosurgical excision. Has the time come for a reassessment?

OBJECTIVE: To review the results of a policy decision to offer selected women with cervical high grade squamous intraepithelial lesions (HSILs) loop electrosurgical excision (LEEP) at the time of their initial colposcopic evaluation. STUDY DESIGN: Sixty-one patients with newly diagnosed cytologic cervical HSIL were evaluated for inclusion in a "see-and-treat" protocol. Fifty of these patients met inclusion criteria and underwent immediate loop excision of the cervical transformation zone at their initial colposcopic visit. RESULTS: Forty-eight of 50 patients that underwent see-and-treat management at their initial colposcopic evaluation had histologic evidence of cervical dysplasia/neoplasia. The positive predictive value of diagnostic colposcopy in this setting was 96%, with a 95% confidence interval (88-99%). Two patients had no pathologic abnormality, for an overtreatment incidence of 4%. CONCLUSION: The selected use of see-and-treat management of cytologic cervical HSIL is feasible, highly predictive and associated with an extremely low incidence of overtreatment. Such management has the potential to increase patient satisfaction and compliance while drastically reducing health care dollars currently directed toward the management of HSIL. Strong consideration should be given to accepting see-and-treat management as a viable alternative in the care of patients with documented cervical cytologic HSIL.

Adolescent↗

The virology of cervical neoplasia: an HPV-associated malignancy.

Human papillomaviruses are present in virtually all cervical cancers and cancer precursors. Understanding the epithelial virology of this group of viruses has greatly influenced current concepts of cervical carcinogenesis, has provided a framework for understanding the biologic basis of many diagnostic criteria, and has led to revised classification schemes, diagnostic testing, and modifications in clinical management. This paper briefly reviews virologic concepts supporting the pathogenetic role of these viruses in cervical neoplasia.

Female↗