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Clinical significance of cellular distribution of moesin in patients with oral squamous cell carcinoma.

PURPOSE: Moesin is a linking protein of the submembraneous cytoskeleton and plays a key role in the control of cell morphology, adhesion, and motility. The aim of the present study was to elucidate the clinical significance of expression patterns of moesin in patients with oral squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: Immunohistochemistry for moesin monoclonal antibody was performed on 103 paraffin-embedded specimens from patients with primary OSCC, including 30 patients with locoregional lymph node metastasis, and in the sections from nude mice transplanted with two cell lines derived from a single human tongue cancer (SQUU-A and SQUU-B). RESULTS: Expression patterns of moesin in OSCCs were divided into three groups: membranous pattern; mixed pattern; and cytoplasmic pattern. These expression patterns correlated with tumor size, lymph node metastasis, mode of invasion, differentiation, and lymphocytic infiltration. In about two-thirds of the patients with metastatic lymph node, homogeneous cytoplasmic expression was detected in the metastatic lymph nodes. In addition, SQUU-B with high metastatic potential showed more reduced levels of membrane-bound moesin than SQUU-A with low metastatic potential. A multivariate analysis demonstrated that expression patterns of moesin can be an independent prognostic factor. CONCLUSIONS: Our results suggest that moesin expression contributed to discriminating between patients with the potentiality for locoregional lymph node metastasis and those with a better prognosis and might improve the definition of suitable therapy for each.

Adult↗

Anterior uveal and episcleral metastases from carcinoma of the breast.

Breast carcinoma is the most common primary tumor producing intraocular metastasis. Metastases to the iris and ciliary body are relatively rare. The authors report a case of a 61-year-old lady, operated for carcinoma of the left breast 3 years back, who presented with symptoms and signs of acute narrow-angle glaucoma in the right eye. A diffuse whitish plaque-like mass in the upper nasal quadrant of the iris with an episcleral nodule on the limbus in the corresponding area and all the signs of acute narrow-angle glaucoma were present in the right eye. Intraocular pressure was controlled medically. Fine-needle aspiration cytology from the episcleral nodule showed malignant cells. Histopathology of the excised nodule showed metastatic poorly differentiated carcinoma, and the cellular pattern was similar to the carcinoma of the breast. There was no other metastasis anywhere in the body. Fine-needle aspiration cytology from an external lesion of the eye is a less invasive and easier procedure than paracentesis to diagnose the metastatic nature of the lesions. The rare features in our case are the clinical presentation as acute glaucoma and the ocular structures being the first and only site of metastasis.

Biopsy, Needle↗

Carcinoma of the penis metastasizing to the dorsal spine. A case report.

Carcinoma of the penis tends to have a predictable route of spread by direct invasion and by regional lymphatic involvement to the inguinal group of lymph nodes. Blood-borne distant spread is rare, last to occur, and is seen in 1-3% of cases. Metastasis to the spine is even rarer. We encountered one such case who presented with spinal metastasis, as documented by the whole body bone scan, and this was later followed by involvement of the inguinal nodes. This case is unique in its site of metastatic presentation as well as its pattern of presentation.

Aged↗

Binding of T-antigen-bearing neoglycoprotein and peanut agglutinin to cultured tumor cells and breast carcinomas.

Chemical conjugation of appropriate carbohydrate ligands to an inert labeled carrier renders probes available to screen for the presence of respective binding sites. A set with a certain plant lectin and a suitable neoglycoprotein can thus determine complementary parts of a potentially relevant glycobiological interaction system. Owing to the interest in the peanut agglutinin-reactive T-antigen, we performed chemical synthesis of the respective disaccharide structure to serve as glycohistochemical ligand and established refinements of the synthetic patway. Coupling of the derivatized monomers had to be performed in the presence of sodium sulfate for optimal results. Complete removal of the protective groups from the p-nitrophenyl derivative of the N-acetylgalactosamine moiety was achieved under mild conditions with 2,3-dichloro-5,6-dicyanobenzoquinone without affecting any other functional groups. Specific binding sites for the synthetic neoglycoprotein as well as for the plant lectin were demonstrated in cell lines of human breast carcinoma colon adenocarcinoma, and erythroleukemia. ABC reagents in conjunction with DAB as peroxidase substrate were used to visualize specific binding sites. Binding complied with the accepted criteria for specificity. Moreover, carbohydrate-specific binding sites were detected in sections of nine out of 14 cases with malignant breast lesions. The percentage of positive tumor cells with both neoglycoprotein and lectin was similar in each of the individual sections, regardless of quantitative variations between cases, lectin staining intensity often being more pronounced. The reactivity pattern in sections of primary and metastatic lesions was not significantly correlated with the lymph node status. This study emphasized that custom synthesis of saccharides and histochemical application of the resulting neoglycoprotein has a remarkable potential for complementary assessment of endogenous binding sites for carbohydrate structures, localized by external tools such as plant lectins, as a step to elucidate the importance of a putative proteincarbohydrate interaction.

Adenocarcinoma↗

The reverse target sign in liver disease: a potential ultrasound feature in cirrhotic liver nodules characterization.

In patients with suspected liver disease, ultrasound is the most commonly performed initial imaging modality. We report a patient who had previously undiagnosed liver cirrhosis with target-shaped lesions interspersed throughout the liver parenchyma on ultrasound seen as multiple uniform round shaped lesions with varying isoechoic to hyperechoic centres surrounded by a hyperechoic rim. We have termed this the "reverse" target sign as there is inversion of the typical echoic pattern that is normally seen in metastatic liver disease. We suggest this ultrasound sign may represent a method for differentiating cirrhotic liver nodules from other nodular liver lesions.

Diagnosis, Differential↗

Current epidemiological trends and surveillance issues in brain tumors.

The absence of an overall increase in incidence rates for all primary brain tumors since the 1950s argues against a recently introduced environmental tumorigen impacting these tumors. Historical increases in brain cancer mortality and incidence rates appear to be leveling off following the widespread introduction of CT and MRI scans, indicating that increases in overall rates of malignant tumors are likely to be an artifact of diagnosis and reporting issues. Further studies are needed to understand those tumor types with rates that do appear to be increasing among adults; specifically lymphomas, nerve sheath tumors, pituitary tumors and ependymomas. Patterns of incidence by race, ethnicity, socioeconomic status, and seasonal and regional variation would assist in directing relevant new research questions. Filling in the gap of information on patterns for prevalent, second primaries and metastatic tumors may be useful in understanding the public perception regarding brain tumor rates and would be a valuable addition to healthcare planning tools.

Brain Neoplasms↗

Renal cell carcinoma presenting as a cervical mass.

The authors report a case of a 60-year-old woman presenting with a renal cell carcinoma in which the first sign leading to its diagnosis was a cervical metastasis, an uncommon site of distant disease in renal neoplasms. The patient had an 18-month history of a progressively enlarging cervical mass at the anterior aspect of the neck. After laboratory and radiological evaluation, the cervical mass was excised, and the microscopic and immunohistochemical patterns suggested the possibility of a metastatic renal cell carcinoma. Computerized tomography of the abdomen showed a solid, 4 cm left renal mass. A radical left nephrectomy was performed, and the histology confirmed the suspected diagnosis. The patient received immunotherapy, and in a follow-up period of 9 months, there was no evidence of recurrent disease. It seems that head and neck metastasis of renal cell carcinoma should preferentially be treated with surgical excision because of the associated morbidity and quality-of-life issues.

Carcinoma, Renal Cell↗

Esophageal aperistalsis secondary to metastatic invasion of the myenteric plexus.

A case of aperistalsis of the esophagus secondary to isolated invasion of the myenteric plexus of Auerbach by metastatic carcinoma is presented. The unique pattern of tumor involvement and the resultant aperistalsis supports the contention that involvement of the neurons in the deep myenteric plexus, either by inflammation or tumor, may be the key factor in producing aperistalsis. No similar cases were found in the literature.

Aged↗

99mTc-labeled macroaggregated albumin in intrahepatic arterial chemotherapy.

One hundred eighty-four 99mTc-labeled macroaggregated albumin (99mTc-MAA) perfusion studies were carried out in 39 patients with histologically proven primary (four) and metastatic (35) hepatic neoplasms. Three different patterns of tumor perfusion were observed: (1) increased central radioactivity (33%); (2) decreased central radioactivity (33%); and (3) mixed and/or diffuse radioactivity (33%). Extrahepatic perfusion as evidenced by radioactive localization in the region of the stomach, pancreas, and small bowel was noted in 51%. Its presence was associated with a higher incidence of gastrointestinal complications (45% vs. 16%). Tumor arteriovenous shunting was demonstrated in 38%, showing localization of radiotracer activity in the lungs, and decreased as tumors decreased in size. The use of 99mTc-MAA infusion studies in intrahepatic arterial chemotherapy offers an excellent evaluation of catheter placement and tumor perfusion, in addition to helping to avoid gastrointestinal complications.

Adult↗

[A comparative study on p53 gene mutation in primary human Dukes C colon cancer with that in matched lymph node metastasis].

OBJECTIVE: To study the relationship between metastasis of colon cancer and the mutation of p53 gene. METHODS: PCR-SSCP was used to analyse exon 5-9 of the p53 gene in 73 cases of Dukes C human primary cancer and 40 cases of matched lymph node metastasis. RESULTS: Mutations were identified in 27 of 73 primary cancers (37%) and 19 of 40 lymph node metastasis (47.5%) with the overall incidence of p53 mutation being 44%. In 21 of 40 cases in which both primary and metastatic cancers were analysed by SSCP, we found no p53 mutations in both lesions. While the same exon and exactly the same mutated band pattern could be seen both in primary and metastatic cancers in another 12 cases (30%). In addition, the agreement of p53 mutation status in primary cancer to the lymph node metastases was lost in the remaining 7 cases (17.5%). All of the 7 cases were confirmed to have base substitution mutations by DNA direct sequencing. In 5 of 7 individuals, the point mutations were detected only in lymph node metastases but not in the primary cancers and in 2 of 7 cases, two exons were found to have mutations in lymph node metastases while only one or no mutation was identified in the primary cancers. CONCLUSION: Most p53 mutations occurred before metastasis and p53 mutations persist throughout the final stage of the progression and metastasis in colon cancer. Furthermore, the metastasis of colon cancer is accompanied by the emergence of new mutation in p53 gene or metastasis is selected against the p53 mutation, which suggests that the mutations in p53 gene may be related to the metastasis of colon cancer.

Aged↗

[Usefulness of power Doppler sonography for the assessment of subpleural lesions].

We investigated the usefulness of color Doppler power mode imaging for the assessment of subpleural lesions in 48 patients (27 with pneumonia, 4 with pulmonary abscesses, 12 with primary lung cancer, and 5 with metastatic lung cancer). We classified the patterns obtained by color flow imaging of subpleural lesions into six groups: type 0, no color flow; type I, spotty color flow; type II, linear color flow; type III, branchy color flow; and type IV, tortuous color flow, with type IV-A, for partial tortuous flow and type IV-B, for general tortuous flow. The color Doppler power mode proved better than velocity mode in terms of ability to generate clear color flow patterns. Color flow patterns obtained in power mode on the patients with pneumonia differed significantly from the patterns obtained on the lung cancer patients. Although the color flow patterns observed in power mode differed significantly for the benign and malignant groups, no statistically significant differences were observed in velocity mode. These findings illustrated the usefulness of color Doppler power mode imaging as a means of diagnosing benign and malignant subpleural lesions.

Adolescent↗

E-cadherin regulates the function of the EphA2 receptor tyrosine kinase.

EphA2 is a member of the Eph family of receptor tyrosine kinases, which are increasingly understood to play critical roles in disease and development. We report here the regulation of EphA2 by E-cadherin. In nonneoplastic epithelia, EphA2 was tyrosine-phosphorylated and localized to sites of cell-cell contact. These properties required the proper expression and functioning of E-cadherin. In breast cancer cells that lack E-cadherin, the phosphotyrosine content of EphA2 was decreased, and EphA2 was redistributed into membrane ruffles. Expression of E-cadherin in metastatic cells restored a more normal pattern of EphA2 phosphorylation and localization. Activation of EphA2, either by E-cadherin expression or antibody-mediated aggregation, decreased cell-extracellular matrix adhesion and cell growth. Altogether, this demonstrates that EphA2 function is dependent on E-cadherin and suggests that loss of E-cadherin function may alter neoplastic cell growth and adhesion via effects on EphA2.

Breast Neoplasms↗

Differentiation of benign and malignant lymph nodes with contrast-enhanced echolymphography using endoscopic ultrasound-guided puncture.

BACKGROUND/AIMS: Although endoscopic ultrasonography is considered the most useful diagnostic modality for the regional staging, the capability of diagnosing lymph node metastasis based on endoscopic ultrasonography images alone is not sufficient. To improve the capability of differential diagnosis of lymph node enlargement, contrast-enhanced echolymphography was performed using endoscopic ultrasonography-guided puncture. METHODOLOGY: Contrast-enhanced echolymphography was performed in 8 metastatic lymph nodes surgically resected from patients with gastrointestinal cancers (in vitro study) and also in 55 patients in whom abdominal lymph node swelling was indicated by endoscopic ultrasonography (in vivo study). Lymph nodes were punctured under real-time endoscopic ultrasonography guidance, and carbon dioxide microbubbles were injected to evaluate echo features before and after microbubbles injection. RESULTS: Contrast-enhanced echolymphography of freshly resected metastatic lymph nodes showed nonhomogeneous echo patterns. In regions demonstrating filling defects detected by contrast-enhanced echolymphography, neoplastic infiltration was pathologically observed. In almost all of the malignant lymph nodes studied in vivo, filling defects and heterogeneous enhancements were observed by contrast-enhanced echolymphography. However, contrast-enhanced echolymphography demonstrated uniform patterns in most of the benign group. The sensitivity, specificity, positive and negative predictive value, and accuracy of differential diagnosis by contrast-enhanced echolymphography were 95.8%, 90.3%, 88.5%, 96.6%, and 92.7%, respectively. CONCLUSIONS: Contrast-enhanced echolymphography is a useful method for help in the differentiation between reactive and malignant alterations of lymph nodes.

Adult↗

[Case of leptomeningeal carcinomatosis effectively treated with intrathecal chemotherapy using ventriculoperitoneal shunt].

A 70-year-old man presented with dizziness, headache and hearing loss. He was admitted to our hospital because of increasing unsteadiness of gait. Magnetic resonance imaging of the brain revealed meningeal thickening with enhancement. The lumbar puncture revealed high opening pressure. The cerebrospinal fluid showed pleocytosis, high carcinoembryonic antigen (CEA) concentration, and presence of neoplastic cells, leading to the diagnosis of leptomeningeal carcinomatosis. Systemic investigation for primary neoplasm identified a Bormman type 3 gastric cancer (papillary adenocarcinoma with micropapillary pattern). Except for the meninges, no metastatic lesions could be detected. A ventriculoperitoneal shunt (Codman Hakim Programmable Valve) was placed for management of intracranial hypertension and intrathecal chemotheray. He was started on oral S-1 (TS-1) combined with intrathecal methotrexate injection using the VP shunt reservoir. In two weeks, headache and hearing loss completely disappeared and gait disturbances started to improve. CSF findings also improved remarkably with disappearance of neoplastic cells and almost normalization of CEA. For the next five months, he was well on oral S-1 and monthly intrathecal chemotherapy, being able to walk using a walker and to stay at home. He subsequently developed posterior cortical symptoms such as prosopagnosia and cortical blindness and gradually lapsed into coma. He died from pneumonia one year after the onset of neurological symptoms. At autopsy, primary gastric cancer was found but much reduced in size. No peritoneal metastasis could be found. In the brain, leptomeningeal carcinomatosis involved the occipital lobes, the base of the temporal lobe, and the cerebellum. We suggest that intrathecal chemotherapy using ventriculoperitoneal shunt with programmable valve system could be an effective method for the treatment of meningeal carcinomatosis.

Adenocarcinoma, Papillary↗

[Dynamic MRI of liver tumors--evaluation by inversion recovery snap shot FLASH MR imaging].

We have studied 20 patients with liver tumor (hepatoma 12, hemangioma 6, metastatic tumor 2) using inversion recovery snap shot FLASH dynamic MR imaging. After intravenous injection of Gd-DTPA, serial 17 images were obtained during 7 minutes. Hepatoma showed central enhancement on early phase (0-20 sec) in 11 patients and absent or less enhancement than surrounding liver parenchyma on late phase (1-3 min) in 12 patients. Hemangioma showed peripheral enhancement on early phase in 6 patients, and slight to moderate enhancement on late phase in 5 patients. Peripheral slight enhancement were seen on late and delayed (5-7 min) phase in two patients with metastatic liver tumor. These characteristic enhancement patterns should facilitate differential diagnosis of liver tumors.

Aged↗

[Echographic semeiotics of metastatic lesions of the liver].

Real-time sonography was carried out in 273 patients with metastatic lesions in the liver. Sonographic patterns of hepatic metastases were identified. Relationships between sonographic semiotics and patterns of primary tumor are discussed.

Adolescent↗

[Invasiveness and metastases of bladder cancer].

An analysis of post-mortem data on 918 cases of bladder cancer established tumor invasion into adjacent tissues in 50.2 +/- 1.61 and metastases--in 36.9 +/- 1.59% of cases. Paravesical fat tissue, the prostate and ureter were the most frequent sites of invasion: 34.7 +/- 1.57, 15.6 +/- 1.20 and 7.5 +/- 0,87%, respectively. Invasion proved to be among the basic risk factors of recurrence development and vesical fistula formation. Tumors were mostly disseminated into lymph nodes (21.6 +/- 1.36), liver (14.9 +/- 1.17) and lung (10.7 +/- 1.02%). A relationship between histologic pattern of tumor and frequency of metastatic spread was found. Bladder cancer extension into the small pelvis and dissemination were frequently the source of diagnostic errors.

Adenocarcinoma↗

Monoclonal antibody against human ovarian tumor-associated antigens.

Mouse monoclonal antibodies (OV-TL 3) were raised against human ovarian tumor-associated antigens for diagnostic purposes. A cloned hybridoma cell line was obtained by fusion of murine myeloma cells with spleen lymphocytes from BALB/c mice immunized with a tumor cell suspension prepared from an ovarian endometrioid carcinoma. The antibodies were initially screened for their ability to bind on frozen sections of human ovarian carcinoma tissue and a negative reaction on gastric carcinoma tissue by indirect immunofluorescence. The reactivity of the selected OV-TL 3 clone (IgG1 subclass) was studied on normal and neoplastic tissues as well as on a cell line derived from the original tumor cell suspension used for immunization. OV-TL 3 antibodies stained frozen sections of human ovarian carcinomas of the following histological types: serous, mucinous, endometrioid, and clear cell. No reaction was found with breast cancers or other nongynecological tumors. No differences in staining pattern were observed between primary and metastatic ovarian carcinomas. OV-TL 3 antibodies brightly stained ovarian carcinoma cell clusters in ascitic fluids and left unstained mesothelial cells and peripheral blood cells. The OV-TL 3-defined antigen also remained strongly expressed on a cell line derived from the endometrioid ovarian carcinoma originally used for generation of OV-TL 3 clone. Reactivity was weak and irregular in a few ovarian cysts, while traces of fluorescence were sometimes detected in epithelial cells lining the female genital tract. In only 3 specimens of 15 endometrium carcinomas was weak focal reactivity with OV-TL 3 antibodies observed. The results of the immunofluorescence study were confirmed by the more sensitive avidin-biotin method and by 125I-labeled OV-TL 3 antibodies. Thus OV-TL 3 recognizes a common antigen for most ovarian carcinomas and may be a useful tool for rapid diagnosis of ovarian carcinomas.

Animals↗