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Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival.

BACKGROUND & AIMS: The E-cadherin-catenin complex plays a critical role in the maintenance of normal tissue architecture. Mutation of any of its components is believed to result in loss of cell-cell adhesion and contribute to neoplasia. The aim of this study was to examine the expression of E-cadherin and alpha-, beta-, and gamma-catenin in gastric carcinoma and dysplasia and determine any relationship with tumor characteristics and survival. METHODS: Immunoperoxidase staining of E-cadherin and alpha-, beta-, and gamma-catenin was performed using 89 gastric carcinomas, lymph node metastases, and gastric biopsy specimens from 14 patients with dysplasia and 10 healthy controls. RESULTS: Membranous staining was observed in control biopsy specimens for all components of the complex. Up to 57% of gastric dysplasia and 90% of tumors stained abnormally for one or more components of the cadherin-catenin complex. Abnormal E-cadherin and gamma-catenin staining occurred more frequently in diffuse than intestinal tumors (P < 0.0005 and < 0.05, respectively). No association with tumor grade or stage was found. A survival advantage was noted in intestinal and diffuse tumors retaining membranous expression of beta-catenin, independent of tumor type, grade, or stage (P < 0.005). CONCLUSIONS: Abnormal expression of the E-cadherin-catenin complex occurs frequently in gastric carcinoma. The close correlation with poor survival suggests that abnormal beta-catenin may be a useful prognostic marker.

Adult↗

Predictors of malignancy in childhood peripheral lymphadenopathy.

PURPOSE: The aim of this study was to identify factors associated with malignant etiologies of childhood peripheral lymphadenopathy and to construct a model that may be used to assess the risk of malignancy. METHODS: The medical records of 60 consecutive patients 18 years old or less who underwent peripheral lymph node biopsies were reviewed. RESULTS: Increasing node size, number of sites of adenopathy, and age were associated with an increasing risk of malignancy (P < .05 for all variables). Graphs useful for risk determination were constructed based on these variables. Additional factors associated with malignancy included the presence of supraclavicular adenopathy (P < .01), an abnormal chest x-ray (P < .01), and fixed nodes (P < .01). Variables that were not statistically different between patients with benign and malignant adenopathy included the duration of adenopathy (P = .43), the presence of fever (P = .36), cough (P = .14), splenomegaly (P = .93), skin involvement (P = .39), tenderness (P = .49), and bilateral adenopathy (P = .39). Fluctuance was associated with benign adenopathy (P < .04). CONCLUSIONS: The risk of malignancy increased with increasing size and number of sites of adenopathy and age. Other significant predictors of malignancy included supraclavicular location, an abnormal chest x-ray, and fixed nodes. These data may be used to supplement clinical judgment to predict the risk of malignancy.

Child↗

[Subjective stress of adjuvant chemotherapy in breast cancer patients].

50 patients, suffering from carcinoma of the breast pT1-3 with concomitant metastatic affection of the lymph nodes with no evidence of distant metastases, and who received adjuvant chemotherapy (either CMF od AC/EC) were examined. Somatic and psychic interferences, the feeling of well-being and general condition, as well as a critical estimation of the clinical situation were assessed. Besides nausea and vomiting, and still prior to hair fall out, chemotherapy activated the memory of the carcinoma. 92% of the patients agreeing to chemotherapy described their decision as having been based exclusively on the medical information. Nevertheless, 30% feel insufficiently informed, so the fear of side effects, the waiting period prior to application, and the confrontation with the seriously ill, were described as a negative experience. An optimistic view with respect to improving the prognosis of the disease were correlated with chemotherapy: 74% would agree to a further chemotherapy. Psychic abnormalities, e.g. depressions, could not be shown following chemotherapy when compared to a reference population.

Adaptation, Psychological↗

Randomized controlled trial of EUS-guided fine needle aspiration techniques for the detection of malignant lymphadenopathy.

BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) is a highly accurate method of detecting malignant lymphadenopathy. The optimal methods for performing EUS-FNA to maximize sensitivity and to minimize the number of needle passes necessary are unknown. This is a report of the results of a prospective randomized controlled trial to determine the effect of suction, the site of FNA (edge or center of lymph node), and the method of preparation of cytologic specimens on accuracy, number of needle passes needed, and specimen quality. METHODS: Consecutive patients with lymphadenopathy detected by EUS underwent FNA. Each lymph node was sampled with or without suction and from the edge or center in a 2 x 2 factorial design. The samples were expressed onto slides for cytology, and the residual material in the needle was analyzed by the cytospin-cellblock technique. Each aspirate was individually characterized for a diagnosis of malignancy, cellularity, and bloodiness. RESULTS: Forty-three patients with a total of 46 lymph nodes were evaluated. The final lymph node diagnosis was benign in 22 (48%), "suspicious for malignancy" in 6 (13%), and malignant in 18 (39%). The use of suction was associated with an increase in the cellularity of the specimen, but did not improve the likelihood of obtaining a correct diagnosis (OR 1.52: 95% CI [0.81, 2.85]). Samples obtained with suction were of worse quality because of excessive bloodiness (OR 4.7: 95% CI [1.99, 11.24]). Aspiration from the edge of the lymph node (compared with the center) did not increase the likelihood of a correct diagnosis (OR 1.16: 95% CI [0.42, 3.21]). For 78% of malignant lymph nodes, the correct diagnosis was obtained on the first needle pass and for 100% by the third pass. Cytospin-cellblock methods did not add any additional diagnostic information compared with direct smear cytology. CONCLUSIONS: The traditional method of applying suction during EUS-FNA does not improve diagnostic accuracy and worsens specimen bloodiness compared with FNA without suction. The site of FNA within the lymph node does not affect accuracy. When EUS-FNA is necessary, our recommendation is up to 3 FNAs without suction from the most convenient and safe location within abnormal-appearing lymph nodes.

Biopsy, Needle↗

Adenocarcinoma of the lung with selective metastasis to the lung: clinical, histologic and DNA-cytofluorometric analyses.

In order to examine selective lung metastasis in lung adenocarcinoma, 7 patients who had died due to metastasis exclusively to the lung were analyzed. Because all of the tumors had been well differentiated adenocarcinoma, 21 cases of well differentiated adenocarcinoma which had metastasized to both the lung and other distant organs were selected as controls. Histologically, 6 of the 7 study cases were bronchiolo-alveolar carcinoma (BAC) of variable cytological type or papillary adenocarcinoma with a thin fibrovascular stroma without apparent destruction of the alveolar wall. There was no difference in clinical findings or nuclear DNA content (NDC) between the BAC and papillary adenocarcinoma with thin fibrovascular stroma. The fibrovascular stroma in the study cases was significantly thinner than that in the control cases (P less than 0.01). Cytofluorometrically, the study cases had a significantly lower and less abnormal NDC than the control cases in terms of the mean NDC and DNA histogram patterns (P less than 0.01 and P less than 0.05, respectively). On the basis of these findings, we conclude that 1) BAC can be classified within the same spectrum as well differentiated papillary adenocarcinoma, and 2) selective lung metastasis occurs in well differentiated adenocarcinomas showing mild NDC abnormalities and having a thin fibrovascular stroma without apparent destruction of the alveolar wall.

Adenocarcinoma↗

Frequent amplification of the cyclin E gene in human gastric carcinomas.

We searched for genetic alterations of the cyclin D1 and cyclin E genes in 45 human gastric carcinoma tissues. Expression of cyclin E mRNA and protein was also analyzed in eight of them by Northern and Western blots and immunohistochemical staining. The cyclin E gene was amplified 3-10 fold in seven gastric cancer tissues (15.6%), of which six were advanced gastric cancers. All of the cases with the cyclin E gene amplification displayed lymph node metastasis. Moreover, the case with the gene amplification overexpressed the cyclin E mRNA and protein. One of eight gastric cancer cell lines, MKN-7, shared the cyclin E gene amplification, and all of the gastric cancer cell lines expressed high levels of the cyclin E mRNA and protein even without gene amplification. Amplification of the cyclin D1 gene was not observed in any of the gastric carcinoma tissues or gastric carcinoma cell lines. These results suggest that the gene amplification and overexpression of cyclin E play an important role in the abnormal growth and progression of gastric carcinoma.

Aged↗

Influence of different criteria for abnormal lymph node size on reliability of computed tomography in patients with non-seminomatous testicular tumor.

The reliability of computed tomography (CT) using different criteria for abnormal size of retroperitoneal lymph nodes (5, 10, 15 mm in largest diameter) was evaluated prospectively in 90 consecutive patients with a non-seminomatous testicular tumor and lymph nodes less than 20 mm at CT. Correlation was made with histologic findings following retroperitoneal lymphadenectomy. Histologic examination revealed metastases in 38 patients (42%). Using a strict criterion of 15 mm for abnormal node size, sensitivity was 37%, specificity 98%, positive predictive value 93% and negative predictive value 68%. A relaxed criterion of 5 mm led to a sensitivity of 71%, specificity 67%, positive predictive value 61% and negative predictive value 76%. Overall accuracy was approximately 70% with the 5, 10 and 15 mm criteria for abnormal size. The inability of a normal scan to exclude metastases was the main limitation of CT.

False Negative Reactions↗

The relevance of internal mammary lymphoscintigraphy in the management of breast carcinoma.

The incidence, implications, and significance of an abnormal internal mammary lymphoscintigram (IML) in 981 breast carcinoma patients without histologic or clinical evidence of axillary metastases is reported. A 13%-16% incidence of parasternal abnormality in patients with early, operable disease correlates well with clinical data. The statistically significant increase, with P consistently less than or equal to 0.005, in incidence of local or distant relapse associated with an abnormal IML when compared to the normal IML emphasizes the value of the procedure as a marker. These results indicate that patients with negative axillae but an abnormal IML should be considered to have stage II disease and should be offered adjuvant therapy. The significance of the IML in determining the true extent of disease in patients with apparent local relapse as well as the prognostic implications of an abnormal IML in 311 patients seen initially with recurrent breast carcinoma is also reported.

Actuarial Analysis↗

[Auto-immune hemolytic anemia associated with Kaposi's sarcoma. Report of a new case (author's transl)].

The association of Kaposi angiosarcomatosis and an auto-immune haemolytic anaemia is reported in a 69-year-old woman. The direct Coombs test was "igG complement" type positive. This is the 5th reported case and the 2nd in which haemolysis developed during an acute malignant exacerbation of the disease. The patient died less than 4 months following the diagnosis of Kaposi's sarcoma, after treatment with prednisone and chlorambucil. Lymphoid and immunological abnormalities are not rare during the course of Kaposi's sarcoma. The reasons are discussed briefly.

Aged↗

[Morpho-immunologic phenotypes of T-cell non-Hodgkin's malignant lymphoma in baboons and their connection with with T-lymphotropic retrovirus STLV-1].

8 cytological types were detected among 58 cases of T-NHL of Papio hamadryas according to human updated Kiel classification (1988). 5 of them were of low grade (lymphocytic, prolymphocytic, T-zone, angioimmunoblastic, small cell pleomorphic) and 3-of high grade (medium and large cell pleomorphic, immunoblastic, large cell anaplastic CD30/Ki-1+). There are differences in a tumor structure and generalization in baboon and human lymphomas in spite of significant similarities. STLV-1 presence (antibodies in blood and virus genome fragments in the lymphoma cell DNA) detected by PCR-amplification in 7 investigated types of baboon T-NHL. CD4+ immune phenotypes were predominant in T-cell baboon lymphomas, while CD8+ phenotypes were rare. Abnormal phenotypes in some cases were also detected in the three-color FACS-analyses.

Animals↗

Major histocompatibility antigens and antigen-processing molecules in retinoblastoma.

BACKGROUND: Malignant transformation of cells is frequently associated with abnormalities in human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLAs mediate interactions of tumor cells with cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Retinoblastoma is the most common intraocular malignant tumor in childhood and is characterized by direct spread to the optic nerve and orbit as well as hematogeneous and lymphatic spread. Little is known about the role of HLA expression in the progression of this malignant disease. METHODS: HLA Class I antigen, beta2-microglobulin (beta2-m), HLA Class II antigens, and the antigen-processing molecules (APMs) of the HLA Class I pathway, including proteasomal subunits (low-molecular mass polypeptide 2 [LMP-2] and LMP-10), the transporter-associated protein (TAP-1) subunit, the binding protein tapasin, and the chaperone molecule calnexin, were studied in 30 archival retinoblastoma specimens by immunohistochemistry. Immunoanalysis was performed based on the International Histocompatibility Working Group Project Description. RESULTS: HLA Class I antigen, beta2-m, HLA Class II antigen, and APMs were positive in 12 tumors with no invasion and were decreased in 13 tumors with choroidal and optic nerve invasion. The difference in HLA and APM expression between the 2 groups was statistically significant (P < 0.001). CONCLUSIONS: Decreased expression of HLA was observed in aggressive tumors and in poorly differentiated tumors. The current findings support a role for both CTLs and NK cell-mediated control of tumor growth in the clinical course of retinoblastoma.

Biomarkers, Tumor↗

An overview and critical analysis of breast cancer screening.

From October 1973 through September 1979, 10,000 women were screened for breast cancer as part of a national project. In this follow-up analysis, we evaluate the current status of 166 women whose tumors were detected by this screening project (women with bilateral malignant neoplasms have been excluded). Mammogram abnormalities only were present in 55 women and abnormal physical findings with or without an abnormal mammogram were present in 111 women. Overall, 75% of patients were diagnosed with stage I (n = 86) or stage II (n = 39) disease. Median follow-up was 117 months. Only eight women (14.5%) whose tumors were detected by mammogram have suffered a relapse. Recurrences have developed in 27 women (24.3%) in the group with abnormal physical findings with or without an abnormal mammogram. Disease-free and relative survival at ten years' follow-up are 79.6% and 83.7%, respectively, for the 166 women whose cancer was detected by mammography only and by physical examination with or without an abnormal mammogram. Further follow-up will be required to determine the impact of screening detection on the natural history of breast cancer.

Adult↗

Chromosomal abnormalities in skin following total body or total lymphoid irradiation.

Patients undergoing bone marrow transplantation often receive total body or total lymphoid irradiation as part of the conditioning regimen prior to marrow infusion. The cytogenetic effects of this therapy on skin fibroblasts were studied. Fibroblast cultures from eight skin biopsies were harvested in early passages for G-banded chromosome analysis. Four biopsies were from three patients who had high-dose cyclophosphamide and total body radiotherapy; one was from within and one was from outside the radiation field of a patient who had high-dose cyclophosphamide and lymphoid radiotherapy, one was from a patient who had combination chemotherapy alone, and one was from a normal control. No abnormal mitoses were found in the control or the patient who had chemotherapy alone, and only two of 30 mitoses from skin outside the lymphoid radiotherapy field were abnormal. However, most cells (49-88%) from five biopsies within radiotherapy fields were abnormal. Typically, abnormal karyotypes were pseudodiploid and contained multiple balanced rearrangements, of which reciprocal translocations were most common. The data indicate that the radiotherapy used for bone marrow transplantation induces extensive, sustained chromosome abnormalities in vivo in skin fibroblasts.

Adolescent↗

Decreased expression of Bax is correlated with poor prognosis in oral and oropharyngeal carcinoma.

We investigated the expression of apoptosis-related factors, p53, Bax, Bcl-2, and spontaneous apoptosis in 57 cases of oral and oropharyngeal squamous cell carcinoma (SCC) by immunochemical staining and ApopTag kit. Positive expression of Bax was inversely associated with advanced tumor stage (P = 0.0225), lymph node metastasis (P = 0.0225), clinical stage (P = 0.0083) and poor prognosis (P = 0.0478). Positive expression of p53 was related to poor prognosis (P = 0.0445) and was associated with negative expression of Bax (P = 0.0439). The apoptosis index did not correlate with clinical outcome. These results suggest that abnormality of Bax expression plays an important role in tumor progression in oral and oropharyngeal SCC.

Apoptosis↗

[The spiral CT of cervical lymph node enlargements. The initial clinical results].

Spiral CT was performed before treatment in 35 patients with suspected cervical lymph node enlargement. By coronary and sagittal reconstruction it is possible to utilise the M/Q quotient which has become accepted as the result of sonographic and MRI examinations. It is now possible to obtain high diagnostic accuracy (97%) for distinguishing between reactive change from metastatic infiltration of lymph nodes (> 8 mm) by using CT. Using spiral CT with 5 mm table movement, three patients diagnosed as stage N1 by axial CT were shown to be N2b. This represents a highly sensitive and highly specific method of lymph node diagnosis. Further diagnostic improvement derives from the ability to relate the lymph nodes to surrounding tissues. Spiral CT is also suitable for defining other space occupying lesions, e.g., the exact extent of retropharyngeal abscesses, abnormalities of the salivary glands or laryngoceles.

Abscess↗

A case of myasthenia gravis associated with thymoma, multiple schwannomas and monoclonal IgA gammopathy.

Myasthenia gravis, malignant thymoma, multiple schwannomas and monoclonal IgA gammopathy coexisted in a 54-year-old Japanese man. Serum acetylcholine receptor antibody activity was located in the IgG fraction, but not in the paraprotein peak. It was speculated that all these disorders might fall under the spectrum of the diseases associated with thymic abnormality or that some growth factors might induce neoplasms and activation of B cell clones of autoantibodies (including acetylcholine receptor antibody) in this case.

Autoantibodies↗