Graziella Abu-Jawdeh

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma

Solid tumors, including endometrial carcinomas, must induce a vascular stroma to grow beyond a minimal size. The mechanisms responsible for angiogenesis in endometrial carcinoma, however, are not well defined. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine that is an important regulator of tumor angiogenesis. We evaluated VPF/VEGF mRNA and protein expression, as well as VPF/VEGF receptor mRNA expression, in endometrial carcinoma.

CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors.

PURPOSE CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44S) as well as several CD44 variant isoforms produced through alternative splicing. Expression of CD44 variants is associated with clinically aggressive behavior in some human tumors. The purpose of the present study is to define the expression of CD44 variant isoforms in ovarian cancer and to investigate whether the expression of these molecules is associated with adverse prognosis. MATERIALS AND METHODS Six specimens of normal ovarian surface epithelium (NOSE) and 31 separate cases of newly diagnosed ovarian cancer were studied by a combination of reverse-transcription polymerase chain reaction (RT-PCR) and immunoperoxidase staining. Clinical correlation was made between CD44 variant expression and stage (I/II v III/IV), residual disease (< or = 2.0- v > 2.0-cm mass), age (< or = 65 v > 65 years), histology (papillary serous v other), grade, and survival. RESULTS RT-PCR analysis revealed that NOSE predominantly expressed transcripts for CD44S, as well as a restricted pattern of transcripts characteristic of CD44 splice variants. CD44S and CD44 variant exon nine sequences (CD44-9v) were focally expressed in one of two NOSE specimens examined by immunoperoxidase staining. In comparison, the majority (71%) of ovarian cancer specimens expressed a complex pattern of CD44 splice variants by RT-PCR analysis. Immunoperoxidase studies revealed that the majority of ovarian cancer specimens expressed both CD44S and CD44-9v, whereas expression of sequences from variant exons 3, 4, and 6 was uncommon. There was no association between CD44 variant expression (transcript or protein) and stage, residual disease, age, histology, grade, or survival. CONCLUSION Expression of CD44S and CD44-9v is a common feature of epithelial ovarian cancer cells. The lack of a significant association between CD44 variant expression and prognosis suggests that other factors may be more important in determining the clinical behavior of this disease.

Endometrial endothelial cells express estrogen and progesterone receptors and exhibit a tissue specific response to angiogenic growth factors.

Objective: To develop a reliable method for the isolation and longterm culture of microvessel endothelial cells from human endometrium and to evaluate their response to angiogenic growth factors and steroid hormones in comparison to endothelial cells derived from other organs.

Recombinant BCG therapy suppresses melanoma tumor growth.

AbstractBackground: Melanoma is the fastest rising cancer in the United States. Bacillus Calmette-Guerin (BCG) has been genetically engineered to actively express and secrete the cytokine interleukin-2 (IL-2). Both BCG and IL-2 have known potent antitumor and immunomodulatory properties. Methods: This recombinant BCG (rBCG 3A) has been tested as an intratumoral injection and a vaccine therapy in conjunction with irradiated tumor cells against melanoma in the murine B16 melanoma model. Results: The transfection process did not adversely after the function of the wild-type (WT) BCG. rBCG 3A and WT BCG are equally effective intratumoral and vaccine therapies against melanoma when compared with normal saline control groups. Tumor burdens were significantly smaller (p</0.01 and 0.05) for the treatment groups for both intratumoral and vaccine administration of therapy. Immunization with rBCG 3A and WT BCG 14 days before a B16 challenge resulted in an ∼45% smaller tumor burden when compared with controls. Conclusions: Novel therapies based on the immunogenic properties of melanoma combined with molecular technologies may offer promise for an effective and safe treatment of melanoma.

Accuracy and consistency in application of a probabilistic approach to reporting breast fine needle aspiration

OBJECTIVE To determine the application of a probabilistic/categorical approach for reporting breast fine needle aspiration (FNA) and its dependence on the cytopathologists level of experience. STUDY DESIGN All breast surgical specimens that had preoperative breast FNA at our institution during a 3-year period were identified. The cytologic results were reported as 1 of 6 categories: positive, suspicious, atypical, epithelial proliferative, unremarkable and nondiagnostic, according to well-defined criteria. Five cytopathologists were responsible for all cytology sing-out during the study period. The histologic and cytologic diagnoses were correlated. RESULTS A total of 297 cases were identified. Overall, there were no false positive cases (positive predictive value [PPV] = 100%). Two false negative cases (negative predictive value [NPV] = 96%) were due to sampling error. This indicates that the PPV and NPV for each of the 5 pathologists were also all 100% except for the 1 pathologist who had two false negative cases due to sampling errors. The probability of finding carcinoma on histology for suspicious and atypical cytologic categories ranged from 67% to 100% and 8% to 31%, respectively, for the individual pathologists. Fifteen cases were signed out by > or = 2 pathologists. The involvement of consultants was significantly associated with diagnosis (P = .02). Ten of the 15 cases were in the suspicious (5) or atypical (5) category. CONCLUSION The probabilistic approach with defined diagnostic criteria is an accurate method and can be consistently applied in reporting breast FNA. Although use of the indeterminate (suspicious and atypical) categories is variable, a definite and considerable difference in the probability of carcinoma between these 2 categories was observed for all pathologists. The involvement of consultants did not move the cases out of these indeterminate categories.

Relative Risk of High Grade Squamous Intraepithelial Lesion Associated With Prior Abnormal Pap Smears

OBJECTIVE Pap smear frequency remains controversial, especially for women with consecutive negative smears. We undertook the current study to ascertain the association of high grade squamous intraepithelial lesions (HSIL) and prior abnormal Paps. STUDY DESIGN Women with biopsy-proven HSIL (cervical intraepithelial neoplasia 2 and 3) diagnosed between September 1996 and December 1997 and age-matched controls with a negative Pap obtained during the same time period were selected. RESULTS Sixty-three cases (mean age = 32 years) of HSIL and 69 controls (mean age = 33 years) constituted the study population. Any prior abnormal diagnosis conferred a 15-fold increased risk of HSIL on the current Pap (50/63 vs. 14/69, P < .0001). When limited to the 60 women with at least three prior Paps, the odds ratio for HSIL on the current Pap with any prior abnormal was 18 (28/31 vs. 10/29, P < .0001). Three cases had at least three consecutive negative Paps prior to the diagnosis of HSIL. CONCLUSION Women with one or more prior negative Pap smears had a significantly decreased risk of HSIL on the current Pap. Consecutive negative Paps did not appear to further decrease the risk; 10% of HSIL patients had had three or more consecutive prior negative Paps. To detect HSIL at its earliest stage, women should be advised to continue annual Pap screening in spite of consecutive negative results.