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Biomedical subjects

Ahmed Shabaik

Publications and source records attributed to Ahmed Shabaik.

10 recordsLinked to original sources

Expression of BAG-1 protein correlates with aggressive behavior of prostate cancers.

BACKGROUND: Differences in tumor behavior, ranging from indolent to aggressive, create a need for novel prognostic biomarkers. BAG-1 is a co-chaperone that regulates the activity of Hsp70, Bcl-2, Raf-1, growth factor, and steroid receptors (e.g., the Androgen Receptor). METHODS: Using immunohistochemical method, we explored BAG-1 expression in prostate cancers and its association with clinicopathological parameters. RESULTS: BAG-1 immunostaining was elevated in prostate cancer compared to normal prostatic epithelium. Higher nuclear BAG-1 in hormone-refractory (n = 34) compared to localized untreated tumors (n = 58) (P < 0.0001) suggested that upregulation of the nuclear isoform may contribute to disease progression. In 64 early-stage patients (T2N0M0) treated with external-beam irradiation, cytosolic BAG-1 correlated with higher pretreatment levels of serum Prostate specific antigen (P = 0.04) and shorter time to disease progression (P = 0.00004). CONCLUSIONS: Increased cytosolic and nuclear BAG-1 expression may denote more aggressive variants of prostate cancer.

Biomarkers, Tumor↗

Framework for parsing, visualizing and scoring tissue microarray images.

Increasingly automated techniques for arraying, immunostaining, and imaging tissue sections led us to design software for convenient management, display, and scoring. Demand for molecular marker data derived in situ from tissue has driven histology informatics automation to the point where one can envision the computer, rather than the microscope, as the primary viewing platform for histopathological scoring and diagnoses. Tissue microarrays (TMAs), with hundreds or even thousands of patients' tissue sections on each slide, were the first step in this wave of automation. Via TMAs, increasingly rapid identification of the molecular patterns of cancer that define distinct clinical outcome groups among patients has become possible. TMAs have moved the bottleneck of acquiring molecular pattern information away from sampling and processing the tissues to the tasks of scoring and results analyses. The need to read large numbers of new slides, primarily for research purposes, is driving continuing advances in commercially available automated microscopy instruments that already do or soon will automatically image hundreds of slides per day. We reviewed strategies for acquiring, collating, and storing histological images with the goal of streamlining subsequent data analyses. As a result of this work, we report an implementation of software for automated preprocessing, organization, storage, and display of high resolution composite TMA images.

Cytodiagnosis↗

Tumor-associated alterations in caspase-14 expression in epithelial malignancies.

PURPOSE: Caspase-14 is unique among caspase family proteases in that its proteolytic processing has been principally associated with epithelial cell differentiation rather than apoptosis or inflammation. We investigated caspase-14 expression in several types of human epithelial malignancy by immunohistochemistry, correlating results with stage, histologic grade, and patient survival. EXPERIMENTAL DESIGN: Tumor-associated alterations in caspase-14 expression were observed for cervical, ovarian, breast, gastric, and colon cancers. RESULTS: In cervical (n = 445), ovarian (n = 91), and colon (n = 106) specimens, expression of caspase-14 was significantly reduced in cancers compared with normal epithelium. Decreases in caspase-14 immunopositivity correlated with the histologic progression of cervical cancer (P < 0.0001, ANOVA). In localized gastric cancers, caspase-14 immunostaining was significantly lower in poorly differentiated tumors compared with well-differentiated tumors (P = 0.02, Pearson's chi(2) analysis). Lower caspase-14 expression was associated with advanced clinical stage in ovarian cancer (P = 0.04, ANOVA) and with shorter overall survival among ovarian cancer patients with serous tumors (n = 62) in both univariate (P = 0.005) and multivariate (P = 0.03) analysis. Lower caspase-14 expression correlated with shorter overall survival among patients with T(3)N(0)M(0) stage gastric cancers (n = 94; P = 0.006, log-rank test). In contrast to cervical, ovarian, and colon cancers, caspase-14 expression was increased in ductal carcinoma in situ and invasive cancers compared with normal mammary epithelium (P = 0.001, t test). CONCLUSIONS: The findings reveal tumor-specific alterations in caspase-14 expression and suggest that differences in its expression may define subsets of epithelial cancers with distinct clinical behaviors.

Biomarkers, Tumor↗

Elevated expression of inhibitor of apoptosis proteins in prostate cancer.

PURPOSE: Inhibitor of apoptosis (IAP) family proteins are suppressors of apoptosis that have been implicated in apoptosis resistance in some cancers. Their expression and relevance to the prognosis of prostate cancer were investigated. EXPERIMENTAL DESIGN: The expression of four members of the IAP family (cellular inhibitor of apoptosis protein 1, cellular inhibitor of apoptosis protein 2, X chromosome-linked IAP, and survivin) was examined by immunohistochemistry and immunoblotting in human prostate cancers and in prostate tissues from transgenic mice expressing SV40 large T antigen under control of a probasin promoter. RESULTS: Tumor-associated elevations in the levels of all four IAP family members were common in prostate cancers of both humans and mice, suggesting concomitant up-regulation of multiple IAP family proteins. Compared with normal prostatic epithelium, increased IAP expression was often evident even in prostatic intraepithelial neoplasia lesions (carcinoma in situ), suggesting that deregulation of IAP expression occurs early in the pathogenesis of prostate cancer. IAP expression did not correlate with Gleason grade or prostate-specific antigen levels. CONCLUSIONS: The findings demonstrate that tumor- associated elevations in the expression of several IAP family proteins occur as a frequent and early event in the etiology of prostate cancer.

Animals↗

Adenomatoid tumor of the pancreas: a case report with comparison of histology and aspiration cytology.

We present a 58-year-old woman who presented with a 1.5-cm, hypodense lesion in the head of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration yielded bland, monotonous cells with wispy cytoplasm, slightly granular chromatin, and small nucleoli. A presumptive diagnosis of a neuroendocrine lesion was rendered. Whipple procedure yielded a well-circumscribed, encapsulated lesion with dense, hyalinized stroma and a peripheral rim of lymphocytes. Spindled and epithelioid cells formed short tubules, cords, and nests. The neoplasm stained for CK 5/6, calretinin, vimentin, CD 99, pancytokeratin, and EMA, consistent with mesothelial origin. This characteristic histology and immunohistochemistry is consistent with an adenomatoid tumor. We believe we are the first to report this benign neoplasm in such an unusual location. Herein we address the diagnosis of adenomatoid tumor by histology, immunohistochemistry, and aspiration cytology. Our case is particularly unique in that the histology and cytology are compared and correlated.

Adenomatoid Tumor↗

Ampullary pancreatoblastoma in an elderly patient: a case report and review of the literature.

Pancreatoblastoma, generally regarded as a pediatric malignant tumor, is rarely found in the adult population. Only 13 adults with pancreatoblastoma, ranging in age from 19 to 68 years, have previously been reported in the world literature. A diagnosis of pancreatoblastoma relies on characteristic histologic features, including epithelial differentiation and, more importantly, squamoid differentiation. Despite aggressive therapy, adults with pancreatoblastoma have a poor outcome. We describe a 78-year-old woman who presented with painless jaundice and was found on abdominal computed tomographic scan to have a 2.7-cm ampullary mass. The patient underwent successful pancreaticoduodenectomy. Pathologic examination of the resected tumor revealed findings characteristic of pancreatoblastoma. The tumor formed acinar and glandular structures, solid areas, and contained many "squamoid corpuscles," a defining feature of pancreatoblastoma. The tumor cells also showed acinar and ductal phenotype by immunohistochemistry. To the best of our knowledge, this case represents the oldest patient with pancreatoblastoma to be described in the literature to date and the first to occur in the ampulla of Vater. We review previously published cases and discuss the clinical and histopathologic features of adult pancreatoblastoma.

Aged↗

Expression of Bcl-2 family member Bid in normal and malignant tissues.

Bid is the only known Bcl-2 family member that can function as an agonist of proapoptotic Bcl-2-related proteins such as Bax and Bak. Expression of the proapoptotic Bcl-2 family protein Bid was assessed by immunoblotting and immunohistochemical methods in normal murine and human tissues, and in several types of human cancers and tumor cell lines. Bid expression in normal tissues varied widely, with prominent Bid immunostaining occurring in several types of short-lived cells (e.g., germinal center B cells, peripheral blood granulocytes, differentiated keratinocytes) and in apoptosis-sensitive cells (e.g., adult neurons). Analysis of Bid expression by immunostaining of 100 colon, 95 ovarian, and 254 prostate cancers, as well as 59 brain tumors and 50 lymphomas, revealed evidence of altered Bid regulation in some types of cancers. Correlations with clinical outcome data revealed association of higher levels of Bid with longer recurrence-free survival in men with locally advanced (T3 stage) prostate cancer (P=0.04). Immunoblot analysis of Bid protein levels in the NCI's panel of 60 human tumor cell lines revealed a correlation between higher levels of Bid and sensitivity to ribonucleotide reductase (RR)-inhibiting drugs (P<0.0005). Overexpression of Bid in a model tumor cell line by gene transfection resulted in increased sensitivity to apoptosis induction by a RR inhibitor. Taken together, these observations suggest a potential role for Bid in tumor responses to specific chemotherapeutic drugs, and lay a foundation for future investigations of this member of the Bcl-2 family in healthy and diseased tissues.

Animals↗

Epithelioid hemangioendothelioma of the lung diagnosed by transesophageal endoscopic ultrasound-guided fine needle aspiration: a case report.

BACKGROUND: Epithelioid hemangioendothelioma is a rare vascular tumor of the lung and is also known as intravascular sclerosing bronchoalveolar tumor. Although it has relatively low malignant potential, extensive pulmonary involvement and systemic metastasis have been described. The cytologic features of these tumors are not very well defined, with only few case reports describing the cytologic findings of epithelioid hemangioendothelioma of the lung on fine needle aspiration. CASE: Endoscopic ultrasound-guided fine needle aspiration of a hilar mass was performed on a 25-year-old female. The cytology showed loosely cohesive sheets and clusters of epithelioid cells. The cellular features included large, irregular nuclei with nucleoli and a moderate amount of vacuolated cytoplasm. Rare cells had a suggestion of cytoplasmic lumen formation. Histologic examination of tissue fragments on the cell block revealed a tumor composed of rounded to spindled epithelioid cells in a background of light blue stroma. The endothelial differentiation was evidenced by cytoplasmic vacuoles and lumens, some of which contained erythrocytes. The endothelial nature of these cells was confirmed by positive staining with factor VIII and CD34. CONCLUSION: The cytomorphologic features of epithelioid hemangioendothelioma described in the literature and observed in our case are distinctive and can help with the interpretation of cytologic smears and prevent misdiagnosis.

Adult↗

Endoscopic ultrasound-guided fine needle aspiration cytology of intraductal papillary mucinous tumor of the pancreas. A case report.

BACKGROUND: Intraductal papillary mucinous tumor (IPMT) of the pancreas is a recently proposed pancreatic tumor entity with a peculiar clinical and pathologic profile. It presents with symptoms that are mostly attributed to the mass effect of the tumor. However, a long history of diabetes mellitus and/or chronic pancreatitis is usually noted. It is thought that IPMT has better prognosis than the usual pancreatic ductal adenocarcinoma and its early identification is important. On imaging studies these neoplasms appear usually as multiloculated, cystic tumors that cannot be easily differentiated from other cystic pancreatic neoplasms. CASE: A 73-year-old, white woman with recent symptoms related to bile duct obstruction and diabetes mellitus and a long history of "chronic pancreatitis" was found to have a pancreatic mass on computed tomography. Endoscopic ultrasound-guided fine needle aspiration of the pancreatic mass and dilated pancreatic duct was performed. Cytopathologic examination of the aspirated material revealed large cells with abundant, eosinophilic cytoplasm arranged singly or occasionally in large sheets with complex papillary fragments. Occasional goblet cells or cells with cytoplasmic mucin-containing vacuoles were also noted within the tumor tissue fragments. The nuclei were large, with nuclear size variability and prominent nucleoli. Copious amounts of mucin and numerous muciphages were noted in the background. A diagnosis of "cystic mucinous tumor, cannot rule out invasion," was entertained. The patient underwent partial pancreatectomy. The histologic features of the resected specimen were consistent with IPMT, with focal areas suggestive of early stromal invasion. CONCLUSION: The cytologic features encountered in the aspirate of this tumor are highly suggestive of IPMT and can help differentiate it from other pancreatic tumors with mucin production, such as the classic mucinous cystic neoplasm and the more common ductal carcinoma.

Adenocarcinoma, Mucinous↗