Immunohistochemical Staining For Neuron-specific Enolase Research Articles

Clinical and Pathological Predictor Factors of Fellow Eye Affliction in Patients with an Initial Unilateral Retinoblastoma

Objective:To identify the clinical and pathological predictor factors for the fellow eye affliction (asynchronous bilateralization) in patients who were initially diagnosed with unilateral retinoblastoma. Methods:The present study was conducted in the Department of Ophthalmology of the Faculty of Medicine at Zagazig University in Zagazig, Egypt. All patients initially diagnosed with unilateral retinoblastoma from January 2005 to December 2007 were followed up meticulously for at least 32 months for the development of metastatic disease and/or fellow eye affliction. At pathological examination, all specimens were stained with hematoxylin (HX) and eosin (E). The specimens also underwent special immunohistochemical staining for neuron-specific enolase (NSE). Care was given to detect optic nerve invasion by the tumor, tumor focality, and tumor differentiation during pathological examination. Results: Only 3 (16.7%) of the 18 patients initially diagnosed with unilateral retinoblastoma developed a fellow eye affliction, asynchronous bilateralization of retinoblastoma, during the follow-up period. The time lapse to fellow eye affliction ranged from 3 to 14 months. All 3 patients (100%) were diagnosed at less than 12 months of age (mean, 6.3 months; P 0.05). Of the 3 patients, 2 (66.7%) had a positive family history of retinoblastoma (P < 0.05). Optic nerve invasion and poor tumor differentiation were found in 2 (66.7%) and 1 (33.3%), respectively, of the 3 patients with asynchronous bilateralization. A statistically significant correlation was found between negative NSE staining and asynchronous bilateralization of retinoblastoma (P < 0.05). Conclusions:This study suggests that earlier age at diagnosis (less than 1 year), positive family history, and negative immunohistochemical staining with NSE are possible predictor factors for the development of fellow eye affliction in patients initially diagnosed with unilateral retinoblastoma.

Neuroendocrine differentiation as an indicator of chemosensitivity and prognosis in nonsmall cell lung cancer

Context: Nonsmall cell lung cancers with neuroendocrine differentiation (NSCLC-ND) may demonstrate biologic behavior intermediate between NSCLC and small cell lung cancer (SCLC) with impact on prognosis.Methods: We analyzed 116 consecutive patients with Stage III and IV NSCLC who were diagnosed and treated between 2001 and 2006. Using immuno-histochemical staining for neuron-specific enolase (NSE), chromogranin A (ChrA), and synaptophysin (Syn), 29 (25%) NSCLC-ND were identified.Results: Expression of NSE was present in 22.4%, ChrA in 15.5% and Syn in 14.8% of patients with NSCLC. Therapeutic response was significantly better in the NSCLC-ND group and specimens with > 30% neuroendocrine (NE)-differentiated tumor cells showed favourable therapeutic response (P < 0.05). Multivariate binary logistic regression showed that percentage of NE positive tumor cells was a significant independent prognostic factor associated with a favourable outcome. Receiver operating characteristic (ROC) curves and areas under ROC curves confirmed that percentage of NE-differentiated tumor cells could be useful prediction factor of therapeutic response. Moreover, according to percentage of NE-differentiated tumor cells, optimal cutoffs and related sensitivities and specificities were determined for each markers.Conclusion: Advanced-stage NSCLC with NE tumor cells are clinically less aggressive tumors. Percentage of NE-differentiated tumor cells identifies patients with favourable therapy response to paclitaxel-cisplatin

Small cell carcinoma of the prostate treated with amrubicin

We describe the use of amrubicin hydrochloride to treat small cell carcinoma of the prostate in a 23-year-old man. Initial radiological examinations of the patient revealed a pelvic tumor associated with bilateral hydronephrosis, pelvic lymph node swelling, and lumbar vertebral bone metastases. The pathological diagnosis was small cell carcinoma originating in the prostate, based on positive immunohistochemical staining for neuron-specific enolase, synaptophysin, and myoglobulin; and negative staining for CD3e, CD20, leukocyte common antigen, and CD99. The clinical stage was T4N1M1. A bilateral nephrostomy was performed to improve renal function, and an ileostomy was established to prevent ileus. The first induction chemotherapy consisted of amrubicin 35 mg/m(2) (days 1, 2, 3, monthly). The amrubicin regimen caused a dramatic reduction in tumor size, but could not be continued, because of the occurrence of grade 4 diarrhea. A different regimen was then administered, consisting of one cycle of a 50% dose and a second cycle of a 75% dose of etoposide (100 mg/m(2) days 1, 2, 3), coadministered with carboplatin (AUC 5, plasma concentration curve). Five months after the induction of chemotherapy, the patient suffered respiratory arrest and died.

Ganglion-Like Cells in Relation to C-cell Proliferation of the Thyroid Gland in Rats

We examined the histopathological characteristics of ganglion-like cells in relation to C-cell proliferations of the thyroid gland in CD(SD)IGS, CD(SD) and F344 rats. The incidence of the focus being composed of ganglion-like cells was extremely low, between 0.5% and 2.5%, in each strain of aging (approximately 2 years old) rat. The lesions were histologically classified into 2 different types, the complex or ganglioneuroma types. The complex type was observed in 2/367 female F344 rats and 1/290 male CD(SD) rats, and the ganglioneuroma type was observed in 3/122 female CD(SD)IGS rats and 3/290 male and 2/247 female CD(SD) rats. The ganglion-like cells were characterized by abundant cytoplasm with large, eccentric, round nuclei and prominent nucleoli. They were stained positive by Nissl staining and weakly positive by immunohistochemical staining for neuron-specific enolase, but were negative for calcitonin, synaptophysin and neuronal nuclei. Based on these results, we considered ganglion-like cells to be a variation of C-cells, which originate from the neural crest, with a loss of its characterization.

The structural characteristics and expression of neuropeptides in the esophagus of patients with congenital esophageal atresia and tracheoesophageal fistula

Purpose The aim of this study was to investigate the structural characteristics and the expression of a group of neuropeptides in the esophagus of patients with congenital esophageal atresia and tracheoesophageal fistula (EA-TEF), as well to elucidate the roles of these neuropeptides in the pathogenesis of postoperative incoordination of esophagus after successful surgical repair of EA-TEF. Methods Twenty-four specimens from distal tracheoesophageal fistulas of patients with EA-TEF (EA-TEF group) and 10 esophageal specimens from neonates who died of nonesophageal diseases (control group) were studied. All of the specimens were subjected to routine pathologic study, ultrastructural observation, and immunohistochemical staining for neuron-specific enolase, substance P, vasoactive intestinal polypeptide, and nitric oxide synthase. Results In the EA-TEF group, mitochondria were distributed along the membrane of smooth muscle cell, whereas mitochondria in the control group were distributed along the karyotheca of the smooth muscle cells. The ratio of granulated vesicles to clear vesicles in the varicosity of the intramuscular motor nerve ending of the EA-TEF group (0.520 ± 0.137) was much higher than that in the control group (0.192 ± 0.020, P < .05). The percentages of specimens shown to have positive expression of neuron-specific enolase and substance P in the EA-TEF group (20.8% and 12.5%, respectively) were significantly lower than those in the control group (90% and 80% respectively, P < .05). The percentages of specimens shown to have positive expression of vasoactive intestinal polypeptide and nitric oxide synthase in the EA-TEF group (83.3% and 75%, respectively) were significantly higher than that in the control group (30% and 10% respectively, P < .05). Conclusion Imbalance of neurotransmitters excretion in nerve vesicle, abnormal intrinsic dysplasia of nerve plexus and increased expression of certain neuropeptides were the main characteristics of esophagus with abnormal intrinsic innervation, which may be responsible for the postoperative esophageal dysfunction of EA-TEF.

Primitive Neuroectodermal Tumor in the Spinal Cord of a Brahman Crossbred Calf

A variety of embryonal tumors of the central nervous system, typically malignant and occurring in young individuals, are recognized in humans and animals. This report describes an invasive subdural but predominantly extramedullary primitive neuroectodermal tumor developing at the lumbosacral junction in a 6-month-old Brahman crossbred calf. The tumor was composed of spindloid embryonal cells organized in interlacing fascicles. The cells had oval to elongate or round hyperchromic nuclei, single to double nucleoli, and scant discernible cytoplasm. Immunohistochemical staining for neuron-specific enolase, synaptophysin, and S-100 protein and formation of pseudorosettes suggested neuronal and possibly ependymal differentiation.

Primary small cell carcinoma of esophagus: Report of 9 cases and review of literature

To analyze the clinical manifestations, pathological features and treatment of primary small cell carcinoma (SCC) of the esophagus and to review the literature on this entity. The records of 9 patients with primary esophageal small cell carcinoma were examined and the demographic data, presenting symptoms, methods of tumor diagnosis, and types of treatment given, response to treatment, pathologic findings, and clinical outcome were reviewed. Features of mixed patterns of histological differentiation and lymph node metastases were specifically sought. All the patients reported dysphagia, weight loss and chest pain as the initial symptoms. In 5 cases the tumors were located in the mid-esophagus, 3 cases in the lower third of the esophagus and 1 case in the upper third. The average length of esophageal involvement was 5 cm. They underwent radical resection, regional lymph node clearance and esophageal-stomach anastomosis in thorax or at neck. Two patients had a stage IIa disease, five had a stage IIb disease, and the other two had a stage III disease of International Union Contrele Cancer (UICC). All of them were histologically and immunohistochemically confirmed SCC of esophagus. Immunohistochemical staining for neuron-specific enolase (NSE), synaptophsin (Syn) and chromogranin A exhibited strong immunoreactivity in all specimens. Three of the nine resected specimens showed foci of squamous cell carcinoma in situ. Metastasis was present in 7 of 9 adjacent lymph nodes. All the patients survived the operations and made an uneventful postoperative recovery. They received adjuvant systemic chemotherapy and local radiation therapy after discharge. During follow-up, three patients developed multiple liver, brain, lung and bone metastases and died between 5 and 18 mo after the diagnosis. Three patients developed widespread metastasis disease and died between 18 and 37 mo after the diagnosis. There was no local tumor recurrence in these 6 patients. The other three patients were lost during follow-up. Primary small cell carcinoma of the esophagus is a rare but very malignant tumor. Radical resection combined with chemotherapy and radiotherapy is helpful in limited stage cases.

Establishment and characterization of a new cell line TC-YIK originating from argyrophil small cell carcinoma of the uterine cervix integrating HPV16 DNA

A new cell line, designated TC-YIK, was established from YIK-1 tumor cells, derived from argyrophil small cell carcinoma (ASCC) of the uterine cervix, and serially heterotransplanted into nude mice, integrating human papillomavirus type 16 (HPV16) DNA. The population doubling time of TC-YIK was approximately 21.6 hours at the 119th subculture. Subcutaneous injection of 1 x 10(8) TC-YIK cells into nude mice yielded a solid tumor. The cytologic appearance of TC-YIK was similar to that of YIK-1. The TC-YIK cells contained argyrophil granules and neurosecretory granules in the cytoplasm and showed positive immunohistochemical staining for neuron-specific enolase, serotonin, and chromogranin. Thus, TC-YIK retained the histochemical characteristics of ASCC. The TC-YIK cells contained HPV16 DNA in a multiple-copy integrated form and actively transcribed the integrated HPV16 genome. Amplification of the c-myc oncogene was observed in the TC-YIK cells. These data suggest that TC-YIK is a useful in vitro experimental model of ASCC and that HPV16 and c-myc may play some role in the genesis of this malignant tumor and/or maintenance of the transformed TC-YIK phenotype.

A comparative study of immunohistochemical staining for neuron‐specific enolase, protein gene product 9.5 and S‐100 protein in neuroblastoma, Ewing's sarcoma and other round cell tumours in children

A comparative study of immunohistochemical staining for neuron-specific enolase (NSE), protein-gene product 9.5 (PGP 9.5) and S-100 was made in 71 undifferentiated round cell tumours from 65 children using formalin-fixed tissues and a standard alkaline phosphatase-anti-alkaline phosphatase method. All of 29 neuroblastomas marked for NSE and 27 for PGP 9.5; staining was diffuse and usually strong in all tumour elements, irrespective of the degree of differentiation. Patterns of staining remained consistent in primary, recurrent and metastatic tumours and were not modified by previous chemotherapy. S-100 staining was weak and confined to cell processes and schwannian elements in less than half of the tumours studied. Two primitive neuroectodermal tumours both stained strongly for NSE and PGP 9.5. Staining for NSE was observed in single maturing cells in 3/12 rhabdomyosarcomas and in tubular elements in 2/4 Wilms' tumours; primitive rhabdomyoblasts and undifferentiated renal blastema were negative; seven lymphomas were negative. Six of 17 skeletal Ewing's sarcomas showed light to moderate cytoplasmic staining for NSE and PGP 9.5. The site, histology and clinical course of these marker-positive Ewing's sarcomas showed no distinctive features. Staining for PGP 9.5 is a useful additional marker for neural differentiation in round cell tumours.

Epidermotropic primary neuroendocrine (Merkel cell) carcinoma of the skin with Pautrier-like microabscesses: Report of three cases and review of the literature

Three cases of primary cutaneous neuroendocrine carcinoma involving the face are reported. In the first patient the tumor developed in the scar of a previously excised basal cell carcinoma of the nose, recurred locally, and metastasized to a regional lymph node 2 1/2 years after initial treatment. In the second and third patients the tumors were located on the forehead and were removed with a wide excision. In the second patient the tumor metastasized to regional lymph nodes 1 month after treatment. Light microscopic examination in all patients showed an undifferentiated, small cell, dermal tumor with prominent epidermotropism, forming Pautrier-like microabscesses. Immunohistochemical staining for neuron-specific enolase was positive, and ultrastructural examination revealed numerous cytoplasmic neurosecretory granules and paranuclear aggregates of intermediate-sized filaments. The literature concerning epidermal involvement by primary neuroendocrine carcinoma of the skin is reviewed; the relation with basal cell carcinoma and treatment are discussed.

Primary Differentiated N-euroblastoma of the Orbit

A 49-year-old woman had a 12-year history of a localized left orbital tumor that required five subtotal excisions, orbital radiotherapy, and finally an exenteration. The last procedure was performed after visual function had deteriorated and in order to prevent spread of the tumor into a surrounding compartment. The biopsy specimens from the first four surgeries showed a stromafree spindle cell tumor with benign cytologic features and no mitotic activity, which exhibited palisading of nuclei, imbrication of delicate cytoplasmic processes (neuropil), true perivascular rosettes with cytoplasmic processes oriented perpendicular to vessel walls, and Wright rosettes. The biopsy after radiotherapy and the exenteration specimen contained more polyhedral (gemistocytoid) tumor cells with abundant eosinophilic cytoplasm and tapering cell processes; nuclear pleomorphism without mitotic activity was also seen. Electron microscopy showed the presence of neurosecretory dense-core granules in the perikaryon region of the tumor cells and in the myriad interweaving cytoplasmic processes (neurites); neither Nissl substance nor synapses were identified. Immunohistochemical staining for neuron-specific enolase was positive, but glial fibrillary acidic protein stained negative. This previously undescribed orbital tumor is interpreted as a primary differentiated neuroblastoma without evidence of ganglion cell differentiation that exhibited locally aggressive behavior. The distinctions between neuroblastic and neuroendocrine tumors are discussed.

Paraganglioma of the cauda equina. A histologic, immunohistochemical, and ultrastructural study and review of the literature

We report a case of paraganglioma of the cauda equina and filum terminale. Diagnosis was established by the histologic organoid pattern, immunohistochemical staining for neuron-specific enolase and ultrastructural dense-core neurosecretory granules. A survey of the literature yielded 16 previously reported cases, five of which were described in 1983. This suggests that heightened awareness of this entity will result in a corresponding increase in the reported incidence.