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Identification of genes involved in human mesothelial cancer progression using a modified differential display technique.

A modified differential display method called RNA fingerprinting was used to identify mRNAs that were differentially expressed during human mesothelial cancer progression. We report the isolation of five different clones. Two clones were expressed in the metastatic mesothelioma cell line M1A and the malignant mesothelioma cell line M1, one clone was expressed uniquely in the metastatic cell line M1A and one clone was solely expressed in the normal mesothelial cells. The other clone was downregulated in the metastatic cell line M1A. The different expression patterns were confirmed by Northern blot analysis. Three clones had no homology to known genes, whereas the other two clones had a striking sequence homology to the M130 antigen and rab 12 mRNA, respectively. The clone that contained a high sequence homology to the M130 antigen mRNA was expressed in the mesothelioma cell lines M1 and M1A and not in any further investigated cancer cell line. This sequence tag may be of interest as a specific mesothelioma tumor marker.

Base Sequence↗

Male breast disease: clinical, mammographic, and ultrasonographic features.

PURPOSE: To describe and quantitate the radiological (mammographic and ultrasonographic) characteristics of male breast disease and to report the clinical and pathological findings. MATERIALS AND METHODS: Two-hundred-thirty-six male patients with different male breast diseases, diagnosed at our institution between January 1990 and July 2001, were retrospectively evaluated. The history, physical examination, mammographic and ultrasonographic findings were analyzed. RESULTS: The spectrum of the disease in 236 male patients were gynecomastia (n=206), primary breast carcinoma (n=14), fat necrosis (n=5), lipoma (n=3), subareolar abscess (n=2), epidermal inclusion cyst (n=1), sebaceous cyst (n=1), hematoma (n=1), myeloma (n=1), and metastatic carcinoma (n=2). The distribution of patterns of gynecomastia were; 34% (n=71) nodular, 35% (n=73) dendritic and 31% (n=62) diffuse glandular. Gynecomastia was unilateral in 55% (n=113) and bilateral in 45% (n=93) of the patients. Male breast cancer presented as a mass without microcalcifications in 86% (n=12) and with microcalcifications in 7% (n=1) of patients. The mass was obscured by gynecomastia, partially in two, totally in one patient. The location of the mass was retroareolar in 46% (n=6) and eccentric to the nipple in 54% (n=7) of patients. On ultrasonography (US), the contours were well-circumscribed in 20% (n=3) and irregular in 80% (n=12) of the masses. CONCLUSION: Male breast has a wide spectrum of diseases, some of which have characteristic radiological appearances that can be correlated with their pathologic diagnosis. In the evaluation of the male breast, mammography and US are essential and should be performed along with physical examination.

Adolescent↗

Long-term outcomes following VATS lobectomy for non-small cell bronchogenic carcinoma.

OBJECTIVES: Despite advantages regarding pain and muscle function, video-assisted thoracic surgery (VATS) lobectomy is infrequently performed and is particularly controversial in bronchogenic carcinoma. We have, therefore, reviewed our experience with VATS lobectomy for non-small cell lung cancer (NSCLC) in an attempt to define the long-term results of VATS lobectomy in this setting. METHODS: Patients were selected for surgery on the basis of clinical Stage I or II disease with routine use of thoracic/upper abdominal CT scanning and cervical mediastinoscopy. VATS resection was performed using the endoscopic hilar dissection technique. All related hilar nodes were cleared and supportative sampling of mediastinal stations beyond the reach of mediastinoscopy was undertaken. Perioperative data were collected prospectively and oncologic outcomes were assessed by 6 monthly census. RESULTS: One hundred and fifty eight patients (mean age 66 years) underwent 159 VATS lobectomies for NSCLC between May 1992 and December 2001. One patient underwent staged bilateral resections. Twenty further procedures were uneventfully converted to open thoracotomy (rate=11.2%). The median operation time was 130 min and median operative blood loss was 60 ml. The median postoperative stay was 6 days. One patient (0.6%) died following VATS resection from acute respiratory distress syndrome (ARDS). Two VATS resection patients died following discharge but within 30 days of surgery. Combined, inpatient and 30-day outpatient mortality was, therefore, 1.8%. The stage distribution for resected lesions was: Stage I, 117; II, 33 and III, 8. Mean follow-up was 38 months (range: 1-107). Tumour recurred in 36 patients presenting as local recurrence in the hilum or mediastinum in nine (25%), metastatic disease in 23 (63.9%) and unknown pattern in four (11.1%). Kaplan-Meier calculated probabilities of freedom from cancer related or associated death at 60 months were Stage I, 77.9%; II, 51.4% and III, 28.6%. CONCLUSION: VATS lobectomy is a safe procedure which is associated with a low probability for conversion to open thoracotomy. The patterns of cancer recurrence do not suggest inadequate local clearance while the long-term survival data for Stage I NSLC cases is encouraging. We believe that this technique should become the operation of choice for early stage NSCLC.

Adult↗

[Diffuse pulmonary calcification in a patient with renal insufficiency].

We report the case of a 37-year-old man with chronic renal insufficiency, on hemodialysis, with no respiratory symptoms but whose chest radiograph showed parenchymal consolidation in the middle and upper lung fields. High resolution computed tomography showed a high-attenuating diffuse alveolar pattern that indicated calcium deposits. Bronchoscopy revealed metastatic calcification on the interalveolar septa and bronchiolar and arteriolar. The present report, based on radiologic and bronchoscopic findings, describes the pathogenesis and anatomical distribution of the patient's diffuse pulmonary calcification.

Adult↗

HLA associations in the antitumor response against malignant melanoma.

In this study we analyzed the human leukocyte antigen (HLA) pattern of North American Caucasian patients with metastatic melanoma as compared with the North American Caucasian (NAC) population. We also investigated whether the HLA type of melanoma patients had an effect on their tolerance and response to interleukin-2 (IL-2)-based therapy. Four hundred twelve serologic phenotypes of Caucasian melanoma patients referred to the National Cancer Institute, National Institutes of Health, from February 1989 through December 1993 were collected by typing the patient's peripheral blood lymphocytes. Furthermore, 74 melanoma patients were typed for HLA class II by high-resolution sequence specific primer-polymerase chain reaction. Response rate and treatment-related toxicity in those patients receiving IL-2-based treatment (N = 272) were compared with HLA serologic types. The frequency of four HLA-B alleles was significantly different in the melanoma compared with the NAC population: of these, HLA-B5, -B8, and -B15 had a frequency falling between the NAC and the Northern European population. No other significant differences between melanoma patients and NAC population were noted for other HLA loci. A correlation was noted between HLA-DR3 and -DR4 alleles and decreased tolerance to IL-2, whereas homozygosity for HLA-DR decreased the chance of response. There were no significant associations between HLA type and response. It is unlikely that the associations noted between some HLA-B alleles and melanoma bear significantly on the etiology of the disease. The differences seen between American melanoma patients and the NAC population are probably best explained by geographical ancestry. The association between HLA-DR and tolerance to IL-2 therapy noted in this study may offer insight toward the understanding of mechanisms regulating the cascade of events after the systemic administration of IL-2.

Gene Frequency↗

Detection of melorheostosis on bone scan.

A case of melorheostosis that was first detected by bone scan during the staging evaluation of a patient with metastatic lung carcinoma is reported. The unique pattern of skeletal involvement of melorheostosis allowed its presumptive diagnosis on bone scan, with subsequent radiographic confirmation. A review of this disorder is presented.

Carcinoma, Squamous Cell↗

Pleomorphic adenoma and carcinoma ex pleomorphic adenoma: immunohistochemical demonstration of the association between tenascin expression and malignancy.

AIMS: To investigate tenascin expression in salivary gland tumours. Tenascin is a matricellular protein that has been studied in several tumour types. Its expression has been correlated with tumour morphogenesis as well as with local invasiveness and tumour metastatic behaviour. METHODS AND RESULTS: The distribution pattern of tenascin in a series of 63 pleomorphic adenomas (PA) and 20 carcinomas ex- pleomorphic adenoma (Ca ex PA) was studied immunohistochemically. Ten normal adult salivary glands were used as controls. Tenascin surrounded the excretory ducts of normal adult salivary gland tissue. It was absent in the basement membrane compartment of both benign and malignant mixed tumours. In the interstitial compartment of the extracellular matrix, the fibro-hyaline type expressed tenascin in a statistically significantly (P < 0.001) lower number of PA cases (25%) in comparison with both malignant and benign areas of Ca ex PA (75% and 90%, respectively). In the Ca ex PA group, a statistically significantly difference (P < 0.001) was found in the frequency of tenascin deposits around aggregates of neoplastic cells between metastasizing (73%) and non-metastasizing neoplasms (0%). CONCLUSIONS: These findings strongly support the hypothesis that tenascin deposition is involved in the mechanisms of malignant transformation of pleomorphic adenomas into carcinomas as well as being associated with clinical disease progression.

Adenocarcinoma↗

Expression of VLA-2, VLA-3, and alpha(v) integrin receptors in uveal melanoma: association with microvascular architecture of the tumour and prognostic value.

BACKGROUND: The interaction of the integrin receptors with their ligands (collagen, laminin, fibronectin, and others) has a crucial role during the reorganisation of the extracellular matrix and the metastatic process. The presence of particular vascular patterns in uveal melanoma is associated with the development of metastases. There is some evidence that interactions between the tumour cells and the extracellular matrix are responsible for the shape of these patterns. METHODS: The expression of VLA-2, VLA-3, and alpha(v) integrin receptors was examined by immunohistochemistry on paraffin embedded tumour specimens from 92 uveal melanomas (iris melanomas excluded). Possible correlations between these results and the tumour vascular patterns, the histological features of the tumours as well as the clinical outcome of the patients, were investigated. RESULTS: The expression of VLA-2 in tumours was associated with the presence of vascular networks (p = 0.05). Tumours with less than 25% VLA-3 positive cells infiltrated the sclera more frequently than those with more than 25% VLA-3 cell positivity (p = 0.05). Tumours expressing less than 50% alpha(v) positive cells were associated with the mixed or epithelioid cell type (p = 0.05) and, with less statistical precision, with the presence of extraocular growth (p = 0.07). The univariate logistic regression analysis showed that the risk of developing metastases within the first 5 years after diagnosis did not depend on the expression of the integrin receptors investigated. CONCLUSION: The potential biological importance of the associations between integrin expression and the histopathological features of the tumours found in the present study remains to be elucidated in future experiments. The immunohistochemical detection of VLA-2, VLA-3, and alpha(v) integrins had no prognostic value in our preliminary report.

Case-Control Studies↗

Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility.

BACKGROUND: Previously, proteomic methods were applied to characterise differentially expressed proteins in microdissected pancreatic ductal adenocarcinoma cells. AIMS: To report that CapG and a related protein, gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer; and to describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines. METHODS: CapG was identified by mass spectrometry and immunoblotting. CapG and gelsolin expression was assessed by immunohistochemical analysis on a pancreatic cancer tissue microarray and correlated with clinical and pathological parameters. CapG and gelsolin levels were reduced using RNA interface in Suit-2, Panc-1 and MiaPaCa-2 cells. Cell motility was assessed using modified Boyden chamber or wound-healing assays. RESULTS: Multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. Immunohistochemical analysis of benign (n = 44 patients) and malignant (n = 69) pancreatic ductal cells showed significantly higher CapG staining intensity in nuclear (p<0.001) and cytoplasmic (p<0.001) compartments of malignant cells. Similarly, gelsolin immunostaining of benign (n = 24 patients) and malignant (n = 68 patients) pancreatic ductal cells showed higher expression in both compartments (both p<0.001). High nuclear CapG was associated with increased tumour size (p = 0.001). High nuclear gelsolin was associated with reduced survival (p = 0.01). Reduction of CapG or gelsolin expression in cell lines by RNAi was accompanied by significantly impaired motility. CONCLUSIONS: Up regulation of these actin-capping proteins in pancreatic cancer and their ability to modulate cell motility in vitro suggest their potentially important role in pancreatic cancer cell motility and consequently dissemination.

Adenocarcinoma↗

Skeletal scintigraphy following incidental trauma.

The significance of antecedent trauma in skeletal scintigraphy was assessed in 503 patients, of whom 241 (46%) had prior fracture or tooth extraction. In patients with sufficiently accurate histories for site-by-site analysis, 33 of 131 fracture sites and 16 of 83 dental-procedure sites were positive scintigraphically. In general, the frequency of scan positivity diminished as the interval between trauma and scanning increased, but a significant number of patients showed prolonged uptake at fracture sites. Several patterns of uptake suggested trauma rather than metastatic disease. Knowledge of a history of trauma is often critical in bone scan interpretation.

Bone Neoplasms↗

Interleukin-2-induced hepatic injury involves temporal patterns of cell adhesion in the microcirculation.

The treatment of metastatic cancer with interleukin-2 (IL-2) is limited by systemic toxicities, including hepatic dysfunction. The objective of this study was to determine the cellular mechanisms of IL-2-induced hepatic injury. Intravital microscopy was used for the direct observation of the murine hepatic microcirculation after 2 h, 2 days, and 4 days of IL-2 treatment. At each interval, leukocyte- and platelet-endothelial adherence were observed and quantitated. Simultaneously, sinusoidal perfusion, serum levels of glutamate pyruvate transaminase, and edema were measured as indexes of hepatic toxicity. IL-2 increased neutrophil adhesion acutely in association with decreased sinusoidal perfusion. Leukocyte adhesion subsided at 2 days, but platelet-endothelial interactions were enhanced and 40% of mice receiving IL-2 had microvascular thrombi. These effects occurred in conjunction with decreased sinusoidal perfusion and the development of hepatic edema. After 4 days of IL-2, maximal hepatic edema, hypoperfusion, and increased serum levels of glutamate pyruvate transaminase were associated with increased lymphocyte adhesion and microvascular thrombosis. These data suggest coordinated, temporal roles of leukocytes and platelets in the generation of IL-2-induced hepatic injury.

Animals↗

Eyelid swelling: think of metastasis of histiocytoid breast carcinoma.

Metastatic breast carcinoma may assume many clinicopathological patterns. We here describe a case of histiocytoid breast carcinoma metastasis in the eyelids of a 73-year-old woman. Clinically, the patient presented painless swelling and nodular infiltration of the lateral and medial portions of the eyelids recalling a xanthomatous process or cystic lesions. Physical examination revealed similar lesions on the neck and right thigh. Medical history had revealed breast carcinoma 5 years previously. A biopsy specimen taken from a nodule on the eyelids revealed a relatively symmetric dermal tumor composed mainly of large, uniform, round-to-oval cells embedded in a fibrous stroma with moderate mucin deposits. The cells had abundant, coarsely granular eosinophilic cytoplasm and scant or absent nuclear atypia. No lobular arrangement of the cells or overt ductal formation were seen. Only occasional intracytoplasmic lumina were observed. Most cells demonstrated a positive immunoreaction for carcinoembryonic antigen. It is important to recognize histiocytoid breast carcinoma metastasis in the eyelids, because it may easily be overlooked clinically and histopathologically. This tumor should not be confused histopathologically with other benign and malignant skin tumors containing similar granular cells, but which have a different significance or a different prognosis. The immunohistochemical study, in conjunction with the medical history of the patient, facilitated the diagnosis.

Aged↗

Endobronchial metastasis of hepatocellular carcinoma.

Endobronchial metastasis (EBM) secondary to extrathoracic malignancies is rare among the various modes of pulmonary metastases. Of the many types of extrathoracic tumors capable of EBM, only one case of EBM from hepatocellular carcinoma has been reported, but radiologic findings were not described. We present the radiologic findings of surgically proven EBM in a patient with hepatocellular carcinoma. A chest radiograph revealed a tubular mass-like opacity in the right suprahilar region combined with mild volume decrease of the right upper lobe. Fiberoptic bronchoscopy had erroneously led to a diagnosis of endobronchial aspergilloma. The metastatic lesion was manifested as a branching pattern of enhanced endobronchial mass at the anterior segment of the right upper lobe on computed tomography.

Bronchial Neoplasms↗

Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis.

BACKGROUND: -Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. OBJECTIVE: -To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. DESIGN: -We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. RESULTS: -In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. CONCLUSIONS: -CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.

Adult↗

[Adult Wilms's tumor with histologically dissisimilar lung metastasis].

A 41-year-old man incidentally found to have a right renal and left large lung tumor in the course of screening for liver dysfunction was admitted to our hospital. Needle biopsy of each tumors revealed histologically renal cell carcinoma and pulmonary blastoma. The renal tumor grew rapidly and soon he died of DIC. Autopsy was performed and the final diagnosis was adult Wilms' tumor and its metastasis to the lung. Histological findings of each large tumors showed different histologic pattern. The renal tumor revealed diffuse nephroblastic subtype and the lung tumor showed epitherial type. This is a rare case of Wilms' tumor in terms of its adult onset and different histologic pattern between the primary tumor and its metastatic lesion.

Adult↗

Aberrant methylation of the estrogen receptor and E-cadherin 5' CpG islands increases with malignant progression in human breast cancer.

Loss of expression for both the estrogen receptor-alpha and E-cadherin genes has been linked to disease progression in human ductal breast carcinomas and has been associated with aberrant 5' CpG island methylation. To assess when, during malignant progression, such methylation begins and whether such methylation increases with advancing disease, we have surveyed 111 ductal carcinomas of the breast for aberrant methylation of the estrogen receptor-alpha and E-cadherin 5' CpG islands. Hypermethylation of either CpG island was evident prior to invasion in approximately 30% of ductal carcinoma in situ lesions and increased significantly to nearly 60% in metastatic lesions. Coincident methylation of both CpG islands also increased significantly from approximately 20% in ductal carcinoma in situ to nearly 50% in metastatic lesions. Furthermore, in all cases, the pattern of methylation displayed substantial heterogeneity, reflecting the well-established, heterogeneous loss of expression for these genes in ductal carcinomas of the breast.

Breast Neoplasms↗

[Non-functioning neuroendocrine tumor of the pancreas: report of a clinical case and review of the literature].

The authors report the case of a 26-year-old woman, with a palpable abdominal mass, dyspepsia, pain and weight loss. These symptoms were caused by a non-functioning or biologically inactive neuroendocrine tumour (BINT), weighing 510 g and located in the tail of the pancreas. The treatment opted for was a surgical resection consisting in a distal pancreatectomy. The results of the operation were satisfactory and the woman is now alive and in good health, without recurrence, after 7 years. The authors then go on to analyse the concept of non-functioning neuroendocrine tumours and the problems relating to their symptoms, location and nature. These tumours, which arise, from the pancreatic islet cells, fail to produce a clinical syndrome owing to insufficient peptide production or insufficient release, or concurrent secretion, of inhibitory peptides by the tumour or production of biologically inactive molecular forms of the peptides (without clinical effects). The value of tumour markers and the indications and type of surgery are also discussed according to the different patterns of tumour spread (local, locoregional and metastatic disease). It is stressed that a complete surgical resection is the only curative treatment for these tumours. Encouraging results have been recently obtained by adjuvant treatment with somatostatin analogues, chemotherapeutic agents and/or inteferon.

Adult↗