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Fadi W Abdul-Karim

Publications and source records attributed to Fadi W Abdul-Karim.

14 recordsLinked to original sources
PubMed2006

Molecular evidence for independent origin of multifocal neuroendocrine tumors of the enteropancreatic axis.

Neuroendocrine tumors of the enteropancreatic axis are often multifocal. We have investigated whether multifocal intestinal carcinoid tumors and multifocal pancreatic endocrine tumors arise independently or whether they originate from a single clone with subsequent intramural or intrapancreatic spread. Twenty-four cases, including 16 multifocal intestinal carcinoid tumors and eight multifocal pancreatic endocrine tumors, were studied. Genomic DNA samples were prepared from 72 distinct tumor nodules using laser capture microdissection. Loss of heterozygosity (LOH) assays were done using markers for putative tumor suppressor genes located on chromosomes 9p21 (p16), 11q13 (MEN1), 11q23 (SDHD), 16q21, 18q21, and 18q22-23. In addition, X chromosome inactivation analysis was done on the tumors from eight female patients. Twenty-two of 24 (92%) cases showed allelic loss in at least one tumor focus, including 15 of 16 (94%) cases of multifocal carcinoid tumors and 7 of 8 (88%) cases of multifocal pancreatic endocrine tumors. Eleven of 24 (46%) cases exhibited a different LOH pattern for each tumor. Additionally, 9 of 24 (38%) cases showed different LOH patterns among some of the coexisting tumors, whereas other coexisting tumors displayed the same allelic loss pattern. Two of 24 (8%) cases showed the same LOH pattern in every individual tumor. X chromosome inactivation analysis showed a discordant pattern of nonrandom X chromosome inactivation in two of six informative cases and concordant pattern of nonrandom X chromosome inactivation in the four remaining informative cases. Our data suggest that some multifocal neuroendocrine tumors of the enteropancreatic axis arise independently, whereas others originate as a single clone with subsequent local and discontinuous metastasis.

Adult↗
PubMed2006

The P2X7 receptor: a novel biomarker of uterine epithelial cancers.

OBJECTIVE: To determine expression of the P2X(7) receptor in normal and in cancer uterine tissues. The rationale was that the receptor P2X(7) regulates constitutive apoptosis in uterine epithelial cells, and previous studies showed diminished P2X(7)-mediated apoptosis in cancer uterine cells compared with normal cells. METHODS: A clinical, experimental feasibility study. Normal (n = 42) and cancer uterine tissues (n = 47) were obtained from a total of 72 women ages 25 to 75. End points for P2X(7) mRNA were quantitative PCR and in situ hybridization, and end points for P2X(7) protein were Western blots and immunostaining using anti-P2X(7) antibody. RESULTS: (a) In normal uteri, P2X(7) mRNA and protein were expressed predominantly in the epithelial (endometrial, endocervical, and ectocervical) cells. (b) Expression of the P2X(7) mRNA and protein was absent from endometrial and endocervical adenocarcinoma tissues and from cervical squamous cell carcinoma tissues. (c) In cervical dysplasia, P2X(7) protein was absent in the dysplastic lesions. (d) Semiquantitative analysis using P2X(7) mRNA (normalized in each tissue to the constitutive glyceraldehyde-3-phosphate dehydrogenase) and P2X(7) protein levels (normalized in each tissue to the constitutive tubulin) revealed that P2X(7) mRNA and/or protein levels can distinguish uterine normal from cancer tissues at high degrees of sensitivity (92%, 100%) and specificity (100%, 90%). SUMMARY AND CONCLUSIONS: (a) Levels of the P2X(7) are lower in uterine epithelial cancer tissues than in the corresponding normal tissues. (b) The data suggest that tissue P2X(7) mRNA and protein levels could be used as a novel biomarker to differentiate normal and cancer uterine epithelial tissues.

Adenocarcinoma↗
PubMed2005

Novel Phase I dose de-escalation design trial to determine the biological modulatory dose of the antiangiogenic agent SU5416.

PURPOSE: To determine the biological modulatory dose of SU5416, we employed a novel trial design, where "dose de-escalation" was based on demonstrable biological changes observed at the maximum tolerated dose. If such an effect was shown, dose de-escalation to a predefined dose level would occur to determine if the lower dose exhibited the same amount of pharmacodynamic effect as the higher dose. EXPERIMENTAL DESIGN: Ten patients with advanced solid tumors were enrolled at each dose level. One of the following pharmacodynamic effects was considered significant: (a) a 35% decrease in microvessel density in sequential tumor biopsies and (b) a 35% decrease in blood flow within tumor as assessed by dynamic contrast-enhanced magnetic resonance imaging. In addition, soluble E-selectin, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, and plasma vascular endothelial growth factor were measured sequentially. RESULTS: Nineteen patients were enrolled. Sequential tumor biopsies in all evaluable patients showed an increase in microvessel density. Only one patient met the intended pharmacodynamic end point of >35% reduction in blood flow. There was a significant increase in both soluble E-selectin and soluble intercellular adhesion molecule levels pretreatment versus levels at the time of removal of patients from study (P = 0.04 and P = 0.0007, respectively). Levels of serum fibrinogen rose with therapy. There was a trend toward increase in plasma vascular endothelial growth factor levels. CONCLUSION: SU5416 does not result in decreased blood flow in tumors or a decrease in microvessel density. This corresponds to the lack of clinical activity seen with this agent. Our clinical trial design termed dose de-escalation is a novel approach to determine the in vivo biological effects of targeted therapies in cancer patients.

Adult↗
PubMed2004

Recommendations for the reporting of bone tumors. Association of Directors of Anatomic and Surgical Pathology.

The diagnosis of a bone tumor is often an arduous task, even for the most experienced orthopedic pathologist. As a starting point, the classification of bone tumors is based on a histogenetic perspective encompassing the type of matrix produced (or not produced) by the tumor. In general, the surgical pathology report should include data pertinent to the treatment and prognostication of an individual patient, and the report should be delivered to the clinician in a clear, concise fashion. Reporting of most bone tumors is similar and includes such information as the type of surgery done, anatomic site, histological type and grade of the tumor (if applicable), and the adequacy of surgical margins. Special emphasis is needed for those tumors with distinct and well-established prognostic and therapeutic features such as osteosarcoma and Ewing's sarcoma/peripheral neuroectodermal tumor. Our recommendation emphasizes a standardized protocol for these sarcomas, especially in light of evidence that postchemotherapeutic tumor necrosis is of prognostic significance. It is also important to note that radiographic imaging plays a very important, often critical, role in allowing the pathologist the opportunity to reach the best final diagnosis. This is especially true when a malignant interpretation is contemplated and in subtyping lesions. We recommend close collaboration between musculoskeletal radiologists, clinicians, and pathologists when dealing with complicated neoplasms of bone.

Bone Neoplasms↗
PubMed2003

Analysis of microsatellite instability and X-inactivation in ovarian borderline tumors lacking numerical abnormalities by comparative genomic hybridization.

The genetic events underlying development of ovarian borderline tumors (tumors of low malignant potential) are not well understood. In our previous studies of microdissected samples from serous borderline tumors, comparative genomic hybridization (CGH) and/or fluorescence in situ hybridization (FISH) analyses showed that 3 of 13 tumors had detectable numerical abnormalities; the remaining 10 had none. In the present study, we examined microsatellite instability (MSI) and clonality in this same set of tumors. Although absence of chromosomal imbalances has been associated with the presence of MSI in some types of solid tumors, the extent of MSI in borderline tumors, and its role in their pathogenesis, is unclear. In our set of 13 tumors, no MSI was detected despite analysis with microsatellite markers recommended by the National Cancer Institute for assessment of MSI. Quantitative X-inactivation studies were informative at the androgen receptor gene AR in 9 of the 13 tumors and revealed that each of the 9 tumors was clonal. In two patients, bilateral tumors showed identical patterns of skewed X-inactivation. These studies confirm the clonality of borderline tumors and suggest that some borderline tumors may develop through mechanisms other than chromosomal imbalances or microsatellite instability.

Adult↗
PubMed2002

Ovarian hyperstimulation by LH leads to mammary gland hyperplasia and cancer predisposition in transgenic mice.

Many risk factors for breast cancer are associated with hormonally regulated events. Although numerous mouse models of mammary cancer exist, few address the roles of hormones in spontaneous tumor formation. Here we report that transgenic mice that overexpress LH, resulting in ovarian hyperstimulation, undergo precocious mammary gland development. A significant increase in proliferation leads to ovary-dependent mammary gland hyperplasia. Transgenic glands morphologically mimic those of wild-type pregnant mice and expression levels of multiple milk protein genes are comparable with what is observed at d 14 of pregnancy. In addition to sustained hyperplasia, spontaneous mammary tumors were observed with a mean latency of 41 wk, indicating that chronic hormonal stimulation causes mammary cancer. Although hormonally induced, these tumors lack expression of progesterone receptor, suggesting that following initiating events, the tumors may become hormone independent. This mouse model likely holds great potential as a tool for discovery of hormone-mediated mechanisms of breast cancer and identification of future targets for breast cancer prevention and treatment.

Animals↗
PubMedDate not supplied

Simulation of microcalcifications on specimen radiographs of breast biopsies by inks used in marking the surgical resection margins.

In routine practice, the evaluation of breast excisional biopsy specimens is assisted by the use of various tissue marking inks to delineate surgical margins and preserve tissue orientation. These inks may simulate microcalcifications in specimen and tissue block radiographs. The magnitude of this problem is studied by systematically identifying the factors leading to the creation of this artifact. Samples of fresh tissue from breast reduction mammaplasties were painted separately with fresh wet ink and ink mixed with dried powdery residue. Black India ink and commercial colored tissue inks (the Davidson Marking System) were tested. The painted tissues were radiographed before and after routine paraffin embedding. Routine histologic sections were obtained from each tissue block for microscopic examination. Compared with unmarked controls, samples inked with blue, green, and red inks containing powdery residues showed radiopaque artifacts on radiographs prior to tissue processing. Only the sample marked with red ink showed residual radiopaque artifacts after processing. Microscopically the dried red ink particles were readily distinguishable from microcalcifications on the tissue sections. On the tissue radiographs, the dried ink artifacts were indistinguishable from true microcalcifications. This study demonstrates that some tissue marking inks used in the pathology laboratory are radiopaque. Inks contaminated with particles of dried residue, often present on ink container lids, may appear as artifacts mimicking microcalcifications on specimen and tissue block radiographs, occasionally complicating the histologic localization of mammographically demonstrated microcalcifications. Tissue marking inks should be tested for radiopacity prior to use on breast biopsies. Ink containers should be checked frequently for buildup of dried residue.

Artifacts↗
PubMedDate not supplied

Fine needle aspiration cytology of breast cylindroma in a woman with familial cylindromatosis: a case report.

BACKGROUND: That sweat gland type tumors occur occasionally in the breast is not surprising, as the breast and cutaneous sweat glands are embryologically related. Cylindromas present most commonly as solitary and sporadic dermal nodules on the face and scalp. Cases of multiple cylindromas are dominantly inherited, and the neoplasms are referred to as "turban tumors" when multiple lesions cover the scalp. Primary cylindroma of the breast has been reported once in the past. To the best of our knowledge, the fine needle aspiration cytology of primary breast cylindroma and its occurrence in the setting of familial cylindromatosis have not previously been reported. CASE: A 59-year-old woman presented with an ill-defined left breast mass. She had a personal and family history of dermal cylindromas on the head and face. Fine needle aspiration cytology demonstrated small, uniform cells with oval nuclei and finely granular cytoplasm, with some cells arranged around conspicuous cylinders of dense, acellular material. Excisional biopsy was recommended to exclude adenoid cystic carcinoma. Tissue biopsy revealed a benign cylindroma arising in breast parenchyma. CONCLUSION: Fine needle aspiration cytology of cylindroma very closely mimics that of adenoid cystic carcinoma. Although extremely rare, primary breast cylindroma is another entity to be included in the cytologic differential diagnosis of bland, basaloid cells associated with globular, extracellular material, a finding most commonly associated with adenoid cystic carcinoma.

Biopsy, Needle↗
PubMedDate not supplied

Significance of histiocytes on otherwise-normal cervical smears from postmenopausal women. A retrospective study of 108 cases.

OBJECTIVE: To evaluate the significance of histiocytes on normal cervical smears from postmenopausal women and correlate them with endometrial pathology. STUDY DESIGN: Histiocytes were classified into three types. The clinical history was obtained from cytologic and surgical reports. RESULTS: Among 108 cervical smears, 13 had large, foamy histiocytes (type A), 88 had histiocytes resembling superficial endometrial stromal cells (type B), and 7 had variably sized histiocytes alone or in association with inflammatory or multinucleated cells (type C). Endometrial pathology was identified in 13 patients (12.0%): 4/13 with type A histiocytes (2 endometrial adenocarcinomas, 2 endometrial polyps), 8/88 with type B histiocytes (8 endometrial polyps) and 1/7 with type C histiocytes (endometrial polyp). Among 70 patients with no clinical indications for endometrial sampling except for the presence of histiocytes, 4 demonstrated endometrial pathology (all endometrial polyps). In contrast, endometrial pathology was identified in 9/38 with clinical indications for endometrial sampling. Among the 13 patients with endometrial pathology, 9 had a significant clinical history (sensitivity of 69.2%), and 4 had histiocytes as the only indication for endometrial biopsy (sensitivity of 30.8%). CONCLUSION: A significant clinical history is more predictive of endometrial pathology and outweighs the significance of histiocytes as an indication for endometrial biopsy.

Adenocarcinoma↗
PubMedDate not supplied

Histopathologic correlation of atypical parakeratosis diagnosed on cervicovaginal cytology.

OBJECTIVE: To retrospectively examine the histopathologic findings in women with the isolated finding of atypical parakeratosis (PK) on a Pap test. STUDY DESIGN: The cytology files (1999-2001) were searched for cervicovaginal Pap tests interpreted as atypical PK. Cases were included for study only if there was a subsequent cervicovaginal tissue sample within 1 year of the cytologic interpretation and there was no diagnosis of squamous intraepithelial lesion (SIL) within the previous five years. RESULTS: Of 355 patients with atypical PK, 109 (aged 14-69 years, mean 31.5) met the inclusion criteria of the study. The interval between the cytologic interpretation and cervicovaginal tissue examination ranged from 0.5 to 12 months (mean, 2.5). Sixty-one patients underwent both endocervical curettage (ECC) and cervical biopsy (CBx), 20 patients underwent ECC only, 19 patients underwent CBx only, and the remainder underwent other procedures. Histopathologic findings on the tissue samples included: no significant pathologic change but no squamous epithelium present for evaluation (n = 10, 9.2%), benign changes other than hyperkeratosis and/or PK (n = 50, 45.9%), hyperkeratosis and/or PK (n = 8, 7.3%), low grade SIL (n = 33, 30.3%), high grade SIL (n = 6, 5.5%) and invasive squamous cell carcinoma (n = 2, 1.8%). CONCLUSION: The isolated finding of atypical PK on a Pap test correlated with the presence of an underlying SIL or invasive carcinoma in approximately 40% of patients. Of these, 80% had low grade SIL. The cytologic finding of atypical PK warrants further investigation in order to exclude SILs and/or carcinoma. We suggest that atypical PK be routinely included in the category of atypical squamous cells of undetermined significance.

Adolescent↗
PubMedDate not supplied

Histologic follow-up of atypical endocervical cells. Liquid-based, thin-layer preparation vs. conventional Pap smear.

OBJECTIVE: To review the histologic findings in patients diagnosed with "atypical glandular cells of uncertain significance, endocervical cell type" (AGUS-EC) by ThinPrep Pap Test (TPPT) or conventional Pap smear (CPS) and to evaluate the clinical value of subclassifying AGUS-EC as "favor reactive" or "favor neoplastic." STUDY DESIGN: All TPPT and CPS diagnosed as AGUS-EC (favor reactive, unspecified and favor neoplastic) from January 1998 through December 1999 and all available histologic follow-up (defined as endocervical curettage, cervical biopsy, cervical conization or hysterectomy obtained within six months of the time of an AGUS-EC diagnosis) were obtained from a computerized database. RESULTS: AGUS-EC was diagnosed in 0.77% of CPS (683 of 88,825) and 0.59% of TPPT (183 of 30,968) (P = NS). There was no statistically significant difference in any of the follow-up histologic diagnoses between the CPS and TPPT groups. The majority of the follow-up biopsies demonstrated benign processes in both groups. Patients with a diagnosis of AGUS-EC "favor neoplastic" had a greater proportion of true glandular pathology as compared with AGUS-EC "unspecified" or "favor reactive" (P < .001). None of the patients with a diagnosis of AGUS-EC "favor reactive" were found to have true glandular pathology; however, a minority of them proved to have squamous pathology. CONCLUSION: In this study there was no difference in CPS and TPPT in regard to the specificity of a diagnosis of AGUS-EC for true glandular pathology. Subclassifying AGUS-EC as "favor reactive" or "favor neoplastic" may provide valuable information for directing patient follow-up.

Adenocarcinoma↗