The effects of platelet-derived growth factor and receptor on normal and neoplastic human ovarian surface epithelium.

UNLABELLED: Several growth factors have been shown to stimulate or inhibit the growth of human ovarian surface epithelial (HOSE) cells. Platelet-derived growth factor (PDGF) is likely to be released onto the ovarian surface epithelium during follicular wound repair. We undertook the evaluation of this factor and its receptor in normal and malignant ovarian cells. OBJECTIVES: The goal of this study was to evaluate the response of HOSE cells to PDGF in vitro and identify PDGF receptors on normal and malignant ovarian epithelial cells. In addition, we wanted to examine the prognostic value of the PDGF receptors in clinical specimens. METHODS: Normal HOSE cells were cultured and growth response to PDGF assayed by 3H uptake. PDGF receptor status on HOSE cells, established ovarian carcinoma cell lines, and paraffin tissue was performed by immunohistologic techniques. Data on ovarian cancer patients relapse-free survival (RFS) were abstracted from the Lankenau Hospital Tumor Registry and RFS was plotted using the Kaplan-Meier method. RESULTS: HOSE cells increased 3H uptake in a dose-dependent manner in response to PDGF. HOSE cells stain positively for both alpha and beta receptors, as does the chemotherapy naive cell line A2780. The platinum-resistant CP30 cell line loses PDGF alpha staining. Of 21 ovarian cancer specimens, only 1 retained PDGF alpha receptors while 8 retained PDGF beta receptors. Those patients positive for PDGF receptor beta had a significantly longer relapse-free survival than PDGF beta receptor-negative patients. CONCLUSIONS: PDGF enhances the growth of HOSE cells in vitro and may play a role in ovarian cancer development. Patients whose tumors retain PDGF receptor beta staining positivity have a prolonged relapse-free survival.

Expression of P-cadherin identifies prostate-specific-antigen-negative cells in epithelial tissues of male sexual accessory organs and in prostatic carcinomas. Implications for prostate cancer biology.

Cadherins constitute a family of calcium-dependent cell-cell adhesion molecules the individual members of which are essential for the sorting of cells into tissues during development. In this study, we examined the expression of E-cadherin, N-cadherin, and P-cadherin in tissues obtained from radical prostatectomies. Epithelial cells of prostatic glands, ejaculatory ducts, and seminal vesicles expressed E-cadherin but not N-cadherin. P-cadherin was expressed in epithelial cells of the seminal vesicles and ejaculatory ducts. In the prostate it was limited to the basal cells of prostatic acini, glands with basal cell hyperplasia, and atrophic glands denuded of the luminal cells. All P-cadherin-positive cells were negative for prostatic-specific antigen. Prostatic cancers were mostly P-cadherin negative, but some tumors had P-cadherin-positive areas frequently located close to ejaculatory ducts and negative for prostatic-specific antigen. The mutually exclusive expression of P-cadherin and prostatic-specific antigen suggests that these proteins are involved in differential mechanisms of cell regulation in prostate cancer. P-cadherin may become a useful marker in the diagnosis and management of patients with prostate cancer and low levels of prostatic-specific antigen.

Expression of E-cadherin and N-cadherin in surface epithelial-stromal tumors of the ovary distinguishes mucinous from serous and endometrioid tumors.

This study examines the expression of E-cadherin and N-cadherin in the most common epithelial tumors of the ovary. The homotypic interactions of distinctive members of the cadherin family of cell-cell adhesion molecules segregate cells into tissues during embryonic development, and their expression in tumors can be used to trace the histogenesis of tumor cells. Because the surface epithelium of the ovary is a modified mesothelium, we speculated that the expression of E (epithelial)-cadherin and N (neural, mesodermal)-cadherin may provide clues about the controversial origin of common epithelial ovarian tumors. Immunohistochemistry was performed in paraffin sections using well-characterized monoclonal antibodies to E- and N-cadherin and heat-induced antigen-retrieval methods. We found that serous and endometrioid tumors express both E- and N-cadherin. In contrast, mucinous tumors strongly express E-cadherin, but no N-cadherin. The presence of N-cadherin in serous and endometrioid tumors traces their origin to the mesoderm-derived ovarian surface epithelium. The absence of N-cadherin in mucinous tumors clearly distinguishes them from the former, suggesting histogenesis from a cell lineage other than the ovarian surface epithelium or aberrant differentiation mechanisms associated with neoplastic transformation.

Photo detection of carcinoma of the colon in a rat model: a pilot study.

Photodynamic sensitizers are light-absorbing chemicals that cause photoreactions in biologic systems when exposed to light of the proper wave-length. Dihematoporphyrin ethers (DHE) are the active porphyrin derivatives most commonly used as a photosensitizer (Photofrin, QLT). DHE accumulates in tumor tissue and also fluoresces when light activated. A more reliable and less costly screening method for early detection and treatment of colon cancer is needed. The present study was designed to induce adenocarcinoma of the colon in rats with 1,2 dimethylhydrazine (DMH) and attempt to identify tumors early in their evolution by DHE fluorescence. Forty rats were injected with 20 mg/kg of DMH at weekly intervals until sacrifice. Photofrin (3 mg/kg) was injected through the tail vein in each prior to sacrifice. Eight colonic specimens contained invasive adenocarcinoma, seven of which fluoresced when exposed to a Woods lamp. Carcinoma in situ was identified in two specimens by fluorescence, and one fluorescent specimen contained dysplasia.

The role of perfusion washout in limb revascularization procedures.

Amputated rat hindlimbs were subjected to either normothermic (26 degrees C) or hypothermic (4 degrees C) ischemia. Experimental limbs had their microcirculation washed out (either before or after the ischemic insult) with a physiologic acellular plasma substitute previously reported to enhance flap survival following extended periods of warm ischemia. Control limbs were not washed out; i.e., stagnant blood remained in these limbs. Following the ischemic interval, amputated limbs were replanted. Monastral blue B, a colloidal pigment capable of labeling leaky blood vessels, was administered systemically to all rats just prior to vascular declamping. Limb biopsies of skin and muscle were harvested 30 minutes following revascularization in order to assess Monastral labeling and, therefore, the functional integrity of the microcirculation. Results confirm that stagnant blood under conditions of warm ischemia is detrimental to the functionality of the microcirculation in both skin (p less than 0.03) and muscle (p less than 0.007). Accordingly, perfusion washout, when performed prior to the ischemic period, enhances limb survival following 6 hours of warm ischemia (p less than 0.01). Hypothermia protects against the detrimental effects of stagnant blood; perfusion offers no benefit if hypothermic conditions prevail. Physiologic mechanisms responsible for these findings are discussed.

Delayed microcirculatory hyperpermeability following perfusion washout.

Recent experimental data have demonstrated improved flap survival following perfusion washout with a synthetic, chemically defined, mammalian plasma. In an effort to define the physiology responsible for the efficacy of perfusion, the method of "labeling" hyperpermeable blood vessels with Monastral blue B in rat epigastric vascular island flaps was utilized. Results confirmed that capillary and venular hyperpermeability is an early and progressive pathophysiologic event in ischemic flap tissue and one which is reversible prior to a critical ischemic period. Perfusion washout with a physiologic, acellular plasma substitute delays the onset of vascular hyperpermeability. This may be a mechanism responsible for improving tissue survival following extended periods of warm ischemia (12 hours). It is implied that stagnant blood and products of hemolysis in the microcirculation may be detrimental to the functional and anatomic integrity of the endothelial wall.

Preischemic flap washout and its effect on the no-reflow phenomenon.

Preischemic perfusion washout with an acellular physiologic solution delays the no-reflow phenomenon and improves tissue survival in rat epigastric free flaps following 18 and 24 hours of normothermic ischemia. This implies that stagnating blood may be a causative agent in the no-reflow phenomenon. A possible mechanism for this is capillary endothelial damage secondary to the presence of formed blood cells or their products of hemolysis. Perfusion washout may improve ischemic tolerance by preventing this blood cell-induced endothelial damage and by the prevention of sludge and thrombus. Whether any of the metabolic components of the perfusate actively enhance ischemic tolerance cannot be definitively stated.

Acinic cell carcinoma of the oral cavity.

A rare case of acinic cell carcinoma of minor salivary gland origin within the oral cavity is reported in a 62-year-old woman. These tumors most commonly arise in the parotid gland and follow an insidious course requiring long-term follow-up. The gross and histologic features of the patient's tumor include pseudoencapsulation, mixed solid and acinar architecture, microcyst formation, and the presence of conspicuous diastase-fast and PAS-positive cytoplasmic granules, characteristic of lesions that have been called acinic cell carcinoma by a variety of authors. Surgical excision is the treatment of choice. However, following an incisional biopsy, the patient refused further surgical treatment and has remained clinically disease-free three years postoperatively.

Granular cell tumor of the common bile duct.

Granular cell tumor most commonly appears in the tongue and skin, but has been found in varied locations (10). There are now 14 reported cases of the lesion occurring in the common bile duct. In most of these 14 cases, it has affected black females in their thirties. The lesion is most often benign. It should be considered in the differential diagnosis of obstructive jaundice secondary to bile duct tumors, especially if other granular cell tumors are present. This is the first reported case of pancreaticoduodenectomy for granular cell tumor of the common bile duct.