Ted S. Gansler

Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival

Certain cancers exhibit derangement of de novo fatty acid biosynthesis, manifested as overexpression and hyperactivity of the lipogenic enzyme fatty acid synthase (FAS). Correlation of elevated FAS with high tumor grade and advanced stage in primary breast, prostate, and colorectal cancers has drawn attention to the enzyme as a possible marker of poor prognosis. To find a similar utility of FAS in ovarian neoplasms, we compared FAS expression in 68 ovarian tumors with their histological features and clinical outcome. Immunohistochemical localization of FAS was observed in 48 (71%) cases in which staining was either focal (defined as positive staining in 1% to 20% of cells) or multifocal/diffuse (positive staining in >20% of cells). Most (83%) of the 48 cases were represented by endometrioid, serous, or mucinous carcinomas and malignant mixed mullerian tumors (MMMTs). In contrast, ovarian adenomas and tumors of low malignant potential (LMPs) contained little or no FAS. Association between FAS expression and histological diagnosis was statistically significant. The extent of FAS immunostaining was also predictive of prognosis. Among all patients with ovarian malignancies (including LMPs), median survival was 64.8 months, when their tumors exhibited no or focal immunostaining for FAS, as opposed to 31.2 months, when staining was multifocal/diffuse (P = .005). Similar median survival values were obtained when cases were limited to endometrioid, serous, and mucinous carcinomas. Short-term survival at 1 and 2 years was significantly higher in patients whose tumors showed no or focal expression of FAS compared with multifocal/diffuse expression. Thus, elevated FAS may serve as an independent marker for predicting poor clinical outcome in patients with ovarian cancer.

Raman Spectroscopic Characterization of Human Breast Tissues: Implications for Breast Cancer Diagnosis

Development and application of laser-based diagnostic and therapeutic procedures have been hindered by the current technical inadequacies in tissue diagnosis and characterization. It is now possible to apply the techniques of Raman spectroscopy to achieve rapid, noninvasive, and nondestructive differentiation of diseased from normal tissues. Normal and diseased breast tissues were examined by Raman spectroscopy. The Raman spectra obtained contain features that are attributable to various amounts of carotenoids and lipids. A small contribution from a heme-type signal was detected in some samples of clinically abnormal yet histopathologically benign breast tissue, while a much stronger heme-type signal was detected in most of the breast cancers. Raman spectra of diseased breast tissue (benign and malignant) also show markedly diminished to absent contributions from lipids and reduced contributions from carotenoids. This laser-based spectroscopic modality is readily adaptable to reflected light microscopy and optical fiber techniques, making it potentially useful as an aid in real-time diagnosis, and may thus find application in the fields of histopathology and interventional radiology.

Differential polymerase chain reaction assay of cyclin dl gene amplification in esophageal carcinoma

The cyclin Dl gene, located on chromosome llql3, is frequently rea%anged in parathyroid neoplasms and amplified in some carcinomas of other organs. Recent studies have detected amplification of cyclin Dl and other markers on chromosome 1 lql3 (evaluated by Southern or slot blot assays) in ∼25–50% of squamous cell carcinomas of the esophagus and noted that amplification was associated with lessened survival time. We applied the technique of differentia] polymerase chain reaction to the evaluation of cyclin Dl gene amplification in squamous cell carcinomas of the esophagus. Cyclin Dl was found to be amplified in 10 of 45 (22%) primary tumors and three of 12 (25%) lymph node metastases. Lymph node metastases tended to be more common in patients with cyclin Dl amplification (70%) than in those without amplification (37%). In 36 patients with follow-up. cyclin Dl amplification was associated with decreased 1 year survival (28% vs. 59%). Cyclin Dl gene amplification in esophageal carcinomas can be evaluated by differential polymerase chain reaction and may provide useful prognostic information.

Aspiration cytologic, ultrastructural, and DNA cytometric findings of solid and papillary tumor of the pancreas.

Solid and papillary epithelial neoplasm of the pancreas (SPENP) is a rare lesion characteristically occurring in young women. By contrast with pancreatic ductal adenocarcinomas, SPENP is a slow‐growing tumor that rarely metastasizes or is fatal. The current report describes light and electron microscopic and histochemical findings with DNA flow cytometric analyses of two cases of SPENP. The first patient was a 24‐year‐old woman; the second, a 72‐year‐old man. Although SPENP is rare in older men, both patients had characteristic radiographic and light microscopic features of SPENP. Ultrastructural evidence of acinar differentiation was seen in the first patient; the second patient had focal neuroendocrine differentiation. Flow cytometric analysis of the first tumor demonstrated diploid‐range DNA content with a 5.8% S‐phase fraction (SPF). The DNA cytometric analysis of a biopsy specimen from the second tumor revealed diploid‐range DNA content with a 6.1% SPF, although subsequent sampling of the resected tumor showed an aneuploid population with a DNA index of 1.8 and SPF of 2.1%.

Suramin Inhibits Growth Factor Binding and Proliferation by Urothelial Carcinoma Cell Cultures

Suramin is a polyanionic compound recently noted to inhibit growth factor action and proliferation of several types of neoplastic cells in vitro. Data from clinical trials show antineoplastic activity against some prostatic and adrenal cortical carcinomas. Suramin is excreted unmetabolized into the urine suggesting possible application in treatment of urothelial carcinoma and prompting us to examine the drugs effect on growth factor binding and cell proliferation by two urothelial carcinoma cell lines. Half-maximal inhibition of 125I-epidermal growth factor (EGF) binding to T24 and HT1376 cells was produced by suramin concentration of approximately 300 and 100 microM, respectively. The corresponding value for 125I-insulin-like growth factor 1 (IGF1) binding was 60 microM for both cell lines. Inhibition of T24 and HT1376 growth was virtually complete at suramin concentrations in the range achievable clinically.

Detection of Silicone in Lymph Node Biopsy Specimens by Near-Infrared Raman Spectroscopy

Near-infrared Raman spectroscopy with a 782-nm cw laser was used to examine lymph node biopsy specimens from women with ruptured breast implants containing silicone gel. For reduction of fluorescence and sample radiation damage, a low-power (30 mW) Ti: sapphire laser, single-stage spectrograph, and CCD detector were employed. Silicone Raman features were clearly visible in lymph node tissue of patients with leaking implants, and the spectra were easily distinguished from those of normal lymph node tissue. The technique has promise for medical diagnostic purposes, and may be amenable to in vivo analysis with adaptation to a fiber-optic probe.

Pulmonary malakoplakia diagnosed by fine needle aspiration : A case report

BACKGROUNDnPulmonary malakoplakia is an uncommon disorder, with 24 previously reported cases, only 4 of which were diagnosed by bronchial washings, bronchial brushings or aspiration cytology. We report a case that was diagnosed initially by computed tomography (CT)-guided fine needle aspiration (FNA) cytology.nnnCASEnA 56-year-old male with follicular small cleaved cell lymphoma had a 10-cm left lower lobe mass compressing the main bronchus to that lobe. A transthoracic, CT-guided FNA specimen consisted predominantly of foamy macrophages, many of which contained typical Michaelis-Gutmann bodies. Microbiologic cultures identified Rhodococcus equi. A subsequent transbronchial biopsy and left pneumonectomy specimen confirmed the cytologic diagnosis.nnnCONCLUSIONnPulmonary malakoplakia associated with R equi pneumonia is a rare lesion that is essentially limited to immunocompromised hosts. Awareness of the FNA cytomorphology of this lesion permits resolution of the typical clinical differential diagnosis of pulmonary masses in the immunocompromised host and can facilitate treatment.

Prognostic indicators in male breast carcinoma.

Abstract: Twenty‐nine male breast cancers (MBC) were studied to determine the relationship between expression of several prognostic factors and clinical outcome. Immunohistochemistry employing a labeled streptavidin‐biotin method was used to detect the presence of estrogen (ER) and progesterone receptors (PR), cathepsin D (CD), c‐erbB‐2 oncoprotein, epidermal growth factor receptor (EGFR), and p53; results were visually semiquantitated. DNA ploidy was evaluated by image analysis (CAS 200) of 5 μm fixed embedded Feulgenstained tissue sections. For proliferating cell nuclear antigen (PCNA), nuclear immunostain was quantitated as percentage positive nuclear area (PPNA) by image cytometry (CAS 200). The frequency of expression was ER, 26/29 (89.7%); PR, 19/29 (65.5%); CD, 25/29 (86.2%); c‐erbB‐2, 5/29 (17.2%); EGFR, 4/29 (13.8%); and p53, 9/29 (31%). Twenty‐one (72.4%) were aneuploid; the mean PPNA for PCNA was 37.87% (control 13%). Of 20 patients, 10 (50%) MBC had lymph node metastases; 6 (21%) had distant metastases to lung (1) and bone (5). Five of the patients died of MBC. Excluding the patients with only ductal carcinoma in situ, the 1‐and 5‐year survival rates were 90.5% and 56.3%, respectively. In this comprehensive study of a large number of available prognostic markers, their frequency (with the exception of higher ER and CD) and prognostic significance were similar to that in female breast carcinoma. Among clinical and standard pathologic unfavorable prognostic indicators, age ≥ 62 years was significant (p = .004). Trends toward reduced survival were associated with axillary lymph node metastases (p = .145), ER negativity (p = .058), PR negativity (p = .116), and aneuploid DNA content (p = .201).

Aspiration Cytology of the Conjunctival Surface

OBJECTIVEnTo evaluate a method of obtaining conjunctival cells that utilizes aspiration of the conjunctival surface.nnnSTUDY DESIGNnEighteen eyes from 16 patients with epibulbar lesions underwent aspiration of the conjunctival surface using a tuberculin syringe without a needle. The aspirated cells were prepared by the cytocentrifuge or Millipore filter technique. The lesions were subsequently biopsied, and the cytologic and histologic diagnoses were compared.nnnRESULTSnDiagnoses of the conjunctival lesions, in decreasing order of frequency, were conjunctival intraepithelial neoplasia (dysplasia, carcinoma in situ), squamous cell carcinoma, squamous metaplasia, nevus, lymphoma and inflammation. In this feasibility study, the cytologic diagnosis accurately correlated with the histologic diagnosis in most cases. There were two cases in which the cytologic diagnosis led to the correct histologic diagnosis.nnnCONCLUSIONnAspiration cytology of the conjunctival surface is useful in obtaining diagnostic material and may be used as a guide to where a biopsy should be performed. Limitations include inadequate samples and lack of observer experience.

Raman spectrosopic characterization of human malignant tissues: implications for a percutaneous optical biopsy technique for in-situ tissue diagnosis

Recent advancements in the technique of Raman spectroscopy now make it possible to achieve rapid, minimally invasive and non-destructive characterization of tissues. In order to evaluate the efficacy of this technique for diagnosis, the Raman spectra of normal and neoplastic human tissues (e.g., breast, kidney, liver and colon) were obtained utilizing visible and near-IR excitation. Normal breast tissue and colon adenocarcinoma showed major Raman features due to the presence of carotenoids and lipids. In breast carcinoma, the features due to lipids were attenuated and as fibrosis (desmoplasia) increased, new spectral features attributable to collagen were observed. Samples of normal and neoplastic liver and kidney show unique spectral differences sufficient to permit tissue differentiation.