Alterations of COX-2, HER-2/neu and E-Cadherin protein expression in the prostatic adenocarcinoma: preliminary findings.

Altered expression of the pro-inflammatory enzyme cyclooxygenase (COX)-2, E-Cadherin cell-cell adhesion protein and Human epidermal growth factor receptor 2 (HER-2/neu, a proto-oncogene) are involved in the pathogenesis of several cancers including the prostatic adenocarcinoma (PRCa). However, to date the results of the previous studies in this neoplasm are controversial, and the relationships among expression of these molecules in benign prostatic hyperplasia (BPH) and PRCa are mostly unknown. We hypothesize that "there are alterations of COX-2, HER-2/neu and E-Cadherin protein expression in PRCa". We carried out this study to test our hypothesis and to assess the relationships among these molecules both in PRCa and BPH. We used immunohistochemistry to evaluate the expression of these proteins in the tissue specimens of both BPH (27 cases) and PRCa (45 cases). Immunohistochemical staining patterns verified over-expression of COX-2 and HER-2/neu proteins in PRCa as compared to BPH. Alternatively, there was an aberrant (reduced) E-Cadherin protein expression in PRCa. There were weak positive correlations between COX-2 versus HER-2/neu expression. A weak negative correlation was noted between COX-2 and E-Cadherin expression. In conclusion, there were alterations of COX-2, HER-2/neu and E-Cadherin proteins in PRCa. The molecular alterations of the relevant genes and the therapeutic ramifications (the development of selective inhibitors to COX-2 and HER-2/neu) of these preliminary findings are open to further investigations.

Ultrastructural Changes of the Smooth Muscle in Esophageal Atresia.

Esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is a relatively rare congenital anomaly. Despite the advances in the management techniques and neonatal intensive care, esophageal dysmotility remains a very common problem following EA/TEF repair. Our current study aimed to describe the most significant ultrastructural changes of the smooth muscle cells (SMCs) trying to highlight some of the underlying mechanisms of esophageal dysmotility following EA/TEF repair. Twenty-three biopsies were obtained from the tip of the lower esophageal pouch (LEP) of 23 patients during primary repair of EA/TEF. Light microscopic examination was performed with hematoxylin and eosin (HE), and Van Gieson's stains. Ultrastructural examination was done using transmission electron microscopy (TEM). Histopathological examination showed distortion of smooth muscle layer and deposition of an abundant amount of fibrous tissue in-between smooth muscles. Using TEM, SMCs exhibited loss of the cell-to-cell adhesion, mitochondrial vacuolation, formation of myelin figures, and apoptotic fragmentation. There were also plasmalemmal projections and formation of ghost bodies. Interestingly, SMCs were found extending pseudopodia-like projections around adjacent collagen fibers. Engulfed collagen fibers by SMCs underwent degradation within autophagic vacuoles. Degeneration of SMCs and deposition of abundant extracellular collagen fibers are prominent pathological changes in LEP of EA/TEF. These changes might contribute to the pathogenesis of esophageal dysmotility in patients who have survived EA/TEF.

Morphological changes in varicocele veins: ultrastructural study.

BACKGROUND: Varicocele consists of dilatation of the pampiniform venous plexus and the internal spermatic veins. It is present in 15% of male population and is a common cause of male infertility. OBJECTIVE: To describe the normal structure of the internal spermatic vein and the morphological changes in grade 3 varicocele. METHODS: The authors dissected and analyzed a 2- to 3-cm tract of the pampiniform venous plexus of 20 patients undergoing varicocelectomy for left varicocele and of 10 consecutive patients undergoing surgery for left inguinal hernia. The histological examination was performed with hematoxylin­eosin and Masson trichrome stains. The ultrastructural evaluation was done using both scanning and transmission electron microscopy. RESULTS: Compared with normal internal spermatic veins, varicocele veins showed narrowing and/or obliteration of the lumens, destruction of the endothelial cells, invagination of the intima, and deposition of collagen bundles in the media (light microscopy). The ultrastructural changes in varicocele veins included elongation of the endothelial cells with features of cellular damage, loss of the internal elastic lamina, and the appearance of ghost bodies and degenerative vacuoles in the subendothelial layer. CONCLUSIONS: The authors believe this is the first report analyzing ultrastructual changes in normal human internal spermatic vein samples and in varicocele. The underlying molecular mechanisms of these changes await further studies.

Primary small cell neuroendocrine carcinoma of the urinary bladder: a clinicopathologic, immunohistochemical, and ultrastructural evaluation.

Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder is a rare but aggressive neoplasm that usually exhibits neuroendocrine differentiation. Here, the authors report a case of SCNEC in an 80-year-old man. The patient had gross hematuria and nodular mass involving the wall of the urinary bladder. Total cystectomy was done. The tumor consisted of small, uniform, round, and spindled-shaped cells with chromatin dark nuclei and numerous mitotic figures. The cells were reactive for chromogranin, neuron-specific enolase (diffuse), and keratin (focal). Ultrastructural studies revealed neurosecretory granules and intermediate filaments. The diagnosis of SCNEC with focal high-grade urothelial component was established. No metastasis was found at the time of diagnosis and the patient refused further chemotherapy or radiotherapy. The histogenesis, differential diagnosis, and prognosis of SCNEC of the urinary bladder were discussed.

Phenotypic characterization of the infiltrating immune cells in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma.

BACKGROUND: Immune cell infiltrate is a constant feature in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. This study elaborates on the cells of the immune system present in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. HYPOTHESIS: Here, we hypothesized that "the development of benign nodular prostatic hyperplasia and prostatic adenocarcinoma is associated with numeric alterations of the immune cell infiltrate". MATERIALS AND METHODS: A total of 50 transurethral prostatic resection specimens, each entailing normal prostate, benign nodular prostatic hyperplasia and high grade prostatic adenocarcinoma were evaluated for the density and phenotype of the immune cells using immunohistological methods and mouse monoclonal antibodies decorating T cells (CD3), histiocytes (CD68) and B lymphocytes (CD20). RESULTS: Immune cell infiltrate was composed of T cells, histiocytes and B-lymphocytes. CD(+)3 T lymphocytes and CD68(+) cells were the predominant cell populations. We observed variations in the density of the immune cells among the normal prostate, benign nodular prostatic hyperplasia and high grade prostatic adenocarcinoma. Compared with normal prostate, benign nodular prostatic hyperplasia had a statistically significant high density of immune cells (3.4+/-0.4versus 13.5+/-1.0, P<0.00). In contrast, a significant decrease in the counts of these cells was observed in high-grade prostatic adenocarcinoma compared to benign nodular prostatic hyperplasia (13.5+/-1.0 versus 5.2+/-0.3, P<0.01). CONCLUSIONS: The increased density of immune cells (predominantly CD(+)3 T cells) in benign nodular prostatic hyperplasia suggests that the initial response to cellular damage is mediated by cell-mediated immunity. The decreased density of immune cells in high-grade prostatic adenocarcinoma may reflect immunosuppression. The underlying mechanisms of these numeric variations are open for further investigations.

Histological and ultrastructural features of gastrointestinal basidiobolomycosis.

Basidiobolus ranarum is a fungus found in the dung of amphibians, reptiles, and insectivorous bats. Its structural elements include both hyphae and zygospores. Patients with B. ranarum infection may present with subcutaneous, gastrointestinal, or systemic lesions. Here we report a case of gastrointesinal badidiomycosis in a 13-year-old male child who presented with acute abdomen. Exploration revealed a mass in the ascending colon. On histology, transmural granulomatous inflammation composed of abundant eosinophils, lymphocytes, histiocytes and giant cells was seen. Histochemical stains revealed broad, non-septate, hyphae-like structures surrounded by an eosinophilic sheath. On an ultrastructural level, fungal hyphae, spores, and macrophage-laden crystalloids were observed. The diagnosis of gastrointestinal basidiobolomycosis was established and the patient received antifungal treatment. This paper reviews the relevant literature regarding basidiomycosis, and discusses its diverse clinicopathological features, as well as distinguishing it from other diseases.