Clinical implications of proliferation activity in T1 or T2 male gastric cancer patients

Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.

Clinicopathologic significance of fascin, extracellular matrix metalloproteinase inducer, and ezrin expressions in colorectal adenocarcinoma.

Background: The over expression of fascin, extracellular matrix metalloproteinase inducer (EMMPRIN), and ezrin proteins has been associated with poor prognosis in various carcinomas and sarcomas. However, very few studies have reported the relationship between the expression of fascin, EMMPRIN, and ezrin proteins and the clinico-pathologic parameters of colorectal carcinomas. Aims: The aim was to investigate the relationship between fascin, EMMPRIN, and ezrin proteins in colorectal adenocarcinomas and their correlation with clinico-pathologic parameters. Settings and Design: The expression of fascin, EMMPRIN, and ezrin proteins was studied in 210 colorectal adenocarcinoma patients through immunohistochemical staining. Materials and Methods: Immunohistochemical staining by the avidin-biotin peroxidase method was done. The scoring of each protein expression was done and divided into three groups (negative, low-, and high-expression groups). Statistical Analysis: A chi-square test, and Kendall's tau-b correlation test were used for comparing. Survival analysis was performed using the Kaplan-Meier method with log-rank tests and the Cox proportional hazard model. Results: The percentages of the high-expression group of fascin, EMMPRIN, and ezrin proteins in colorectal adenocarcinomas were 24%, 73%, and 62%, respectively. Weak positive correlations were observed among these protein expressions. An increased expression of the fascin protein was significantly associated with advanced tumor depth and shorter survival times, and a high expression of fascin protein was an independent prognostic factor in univariate and multivariate survival analyses. EMMPRIN and ezrin protein expressions were not associated with the clinico-pathologic parameters. Conclusions: The high expression of fascin protein may be an unfavorable prognostic marker for individual colorectal cancer patients.

Expression of E-Cadherin and alpha-, beta-, gamma-Catenin Proteins in Endometrial Carcinoma

Loss of the cell adhesion molecule E-cadherin is suggested to promote tumor invasion and distant metastasis in tumor development. Recently, it has been proposed that E-cadherin function requires its linkage to the cytoskeleton through catenins. We evaluated the expression of E-cadherin and alpha-, beta-, gamma-catenins in tissues of human endometrial carcinoma, analyzed the patterns of cell adhesion molecules' expression in endometrial carcinoma and investigated the relationship between the statuses of cell adhesion molecules and various clinicopathological factors. This study investigated the immunohistochemical expression of E-cadherin and alpha-, beta-, gamma-catenins in 33 paraffin embedded formalin fixed tissues of endometrial carcinomas. Aberrant E-cadherin, and alpha-, beta-, gamma-catenin expression was observed in 33.3 (11 of 33), 27.3 (9 of 33), 18.2 (6 of 33), and 51.5 (17 of 33) % of the specimens, respectively. Statistically significant correlation was found between aberrant expression of E-cadherin and lymph node metastasis and cell types other than endometrioid adenocarcinoma. Aberrant pattern of gamma-catenin expression was also correlated with deep myometrial invasion. However, alpha-, and beta-catenin expression was not correlated with any clinicopathological parameters. Using the Kaplan-Meier method and log-rank comparison test, abnormal expression of E-cadherin was correlated closely with poor survival (p < 0.05), but cases with loss of both E-cadherin and catenin expression predicted even poorer survival than cases with only one or no aberrant expression in E-cadherin and catenins. We revealed aberrant expression of these cell adhesion molecules among patients with endometrial carcinoma. Aberrant expression of E-cadherin was correlated with lymph node metastasis and cell types other than endometrioid adenocarcinoma, while aberrant expression of gamma-catenin was related with deep myometrial invasion. The expression of E-cadherin might be a possible prognostic factor for endometrial cancer while the expression of catenins may help predict patient's survival.

Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an Indian autosomal recessive limb girdle muscular dystrophy patient : immunochemical analysis and clinical aspects.

Abnormalities of dystrophin are a common cause of muscular dystrophy and testing for dystrophin gene or protein has become a part of routine diagnostic evaluation of patients who present with progressive proximal muscle weakness, high serum creatine kinase concentrations, and histopathological evidence of a dystrophic process. Patients who have no dystrophin abnormalities are assumed to have autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2 mentally normal brothers presented with abnormal gait and protrusion of chest and hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy binding of dystrophin. No detectable deletion was observed in the patient's DNA and his brother with cDMD probes. Dystrophin associated proteins, beta-dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha-sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta-sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal molecular weight but of decreased quantity, beta-dystroglycan was reduced by about 37% while alpha-sarcoglycan was completely absent. This study is a first attempt for a systematic clinical, genetic and molecular investigation of the autosomal recessive LGMD in India.

Localization of cytoskeletal proteins in Pneumocystis carinii by immuno-electron microscopy

Pneumocystis carinii causes serious pulmonary infection in immunosuppressed patients. This study was undertaken to observe the cytoskeletal proteins of P. carinii by immuno-electron microscopy. P. carinii infection was experimentally induced by immunosuppression of Sprague-Dawley rats for seven weeks, and their lungs were used for the observations of this study. The gold particles localized actin, tropomyosin, and tubulin. The actin was irregularly scattered in the cytoplasm of the trophic forms but was much more concentrated in the inner space of the cell wall of the cystic forms called the inner electron-lucent layer. No significant amount of tropomyosin was observed in either trophic forms or cystic forms. The tubulin was distributed along the peripheral cytoplasm and filopodia of both the trophic and cystic forms rather than in the inner side of the cytoplasm. Particularly, in the cystic forms, the amount of tubulin was increased and located mainly in the inner electron-lucent layer of the cell wall where the actin was concentrated as well. The results of this study showed that the cell wall of P. carinii cystic forms is a structure whose inner side is rich in actin and tubulin. The location of the actin and tubulin in P. carinii suggests that the main role of these proteins is an involvement in the protection of cystic forms from the outside environment by maintaining rigidity of the cystic forms.

Endodermal sinus tumor: immunophenotypic expression of a carcinoma

A series of five endodermal sinus tumors was studied for their cytoskeletal and other phenotypic markers. They included 2 ovarian, 2 testicular, and 1 inguinal tumors. The cytoskeletal expression was also studied by gel electrophoresis and immunoblotting. Every tumor was diffusely and strongly immunostained for cytokeratin. By SDS-PAGE and immunoblotting, cytokeratins 8 & 18 were detected. Vimentin was focally coexpressed in 4 cases. The stroma was diffusely immunostained for vimentin. None of them expressed desmin, neurofilament, or glial filament protein. Desmoplakin was expressed only in one ovarian tumor. Alpha-fetoprotein and S-100 protein were also diffusely positive among the neoplastic cells; intracytoplasmic globules were especially strongly immunostained. These findings suggest that endodermal sinus tumors represent a group of pure malignant epithelial neoplasms, and may be regarded as primitive carcinomas.

Role of immunoperoxidase staining in serous effusions.

Immunoreactivity with monoclonal antibodies against epithelial membrane antigen, vimentin, keratin-squamous epithelium, keratin-nonsquamous epithelium and with polyclonal antibodies against keratin, involucrin, S-100 protein, desmin and varies; is directly proportional to-1 antitrypsin was done in 30 pleural and peritoneal effusion fluids; 15 each of benign and malignant origin using the avidin-biotin-peroxidase complex (ABC) technique to differentiate between the mesothelial cells and the adenocarcinoma cells. In the present study we have demonstrated that desmin and S-100 protein are distributed in the cancer cells and the mesothelial cells of the effusion fluids. Neither EMA nor keratin has the specific reactive pattern which could lead to the differentiation of the mesothelial cells from the cancer cells, but vimentin and keratin could be used for the diagnosis of the mesothelial cells since they had maximum reactivities compared to the cancer cells.