Expression of hMSH2 and hMLH1 in colorectal carcinomas with microsatellite instability.
Kim H. Piao Z. Kim JW. Choi JS. Kim NK. Lee JM. Park JH.
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea. email@example.com
Microsatellite instability (MIN) due to defective mismatch repair (MMR) genes has been reported in a subset of sporadic colorectal carcinomas and in the majority of tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. Among the known MMR genes, hMSH2 and hMLH1 genes are known to be predominantly altered in HNPCC patients and MIN-positive tumors. In this study, we examined MIN and the protein expression pattern of the hMSH2 and hMLH1 by Western blot and immunohistochemistry from 32 sporadic colorectal carcinomas. MIN was observed in 6 (18%) colorectal carcinomas. Of the 6 MIN-positive tumors, one case showed no expression of either protein, 3 cases showed an absence of hMSH2 protein expression, one case showed an absence of hMLH1 protein expression and one case showed no altered expression of either protein by immunohistochemistry. The decreased expression of the hMSH2 protein in a tumor compared to the normal mucosa was also observed in 5 of the 6 MIN-positive cases by Western blot analysis. All of the MIN-negative tumors showed expression of both proteins by immunohistochemistry. Thus most of the MIN-positive tumors appear to be directly related to the altered expression of these two genes and can be diagnosed by the examination of protein expression.
The value of PCNA and AgNOR staining in endoscopic biopsies of gastric mucosa.
Irazusta SP. Vassallo J. Magna LA. Metze K. Trevisan M.
Department of Pathology, Faculty of Medical Sciences, State University of Campinas, S.P., Brazil.
The aim of the present study was to examine the usefulness of the quantification of PC10-positive-cells and of Argyrophilic Nucleolar Organizer Regions (AgNORs) in gastric biopsies for the identification of gastric mucosal proliferative lesions. Fifty seven paraffin-embedded endoscopic biopsies were classified into four histologic groups: normal, inflammatory, dysplastic and neoplastic mucosa. The percentage of PC10-positive cells was determined by immunohistochemistry. The AgNOR parameters determined included the total number of all identifiable silver precipitations in the nucleus, the mean number of silver precipitations per cluster, and the presence of morphologically heterogenous silver precipitations. Group comparisons were performed using the Kruskall Wallis and Dunn non-parametric tests with a significance level of 5%. A discriminant analysis (followed by the jack-knife procedure) was performed using the three AgNOR parameters plus the percentage of PCNA-positive cells as the independent variables and histological groups as the dependent variable. All three AgNOR parameters, as well as the percentage of PCNA-stained nuclei, showed their highest values in the carcinoma group. However, no good differentiation among the four histologic groups was obtained using only one of these parameters, since there was always considerable overlap among them. By combining all the parameters in a linear discriminant analysis, we obtained a correct classification in 48 out of 57 cases. Within the classification errors there was only one false positive carcinoma, which was in fact a dysplasia and only one false negative carcinoma erroneously classified as dysplasia. The number of cells with heterogenous AgNORs was the most important parameter for the discriminant analysis. No correlation between PCNA values and the AgNOR parameters could be found, thus indicating that they do not represent the same phenomenon in the cell cycle. We concluded that the use of a combination of various proliferation parameters in a linear discriminant analysis may be helpful for differentiating gastric mucosal lesions. The peculiar AgNOR morphology is an important variable which should be taken in consideration in quantitative studies. PCNA and AgNORs seem to represent different physiological phenomena in the cell cycle.
The pS2 protein in colorectal carcinomas and metastases.
Hackel C. Falkenberg B. Gunther T. Lippert H. Roessner A.
Institute of Pathology, Otto-von-Guericke University, Magdeburg, Germany. firstname.lastname@example.org
Expression of pS2 protein in 50 primary tumors, metastases and recurrent tumors of colorectal carcinomas has been analyzed by immunohistochemistry. Sixty percent of the primary tumors were at least focally positive for the antigen. There was no correlation between pS2 expression and histologic grade of the lesions. In contrast, pS2 expression in T4 and T3 tumors was significantly higher than in T2 carcinomas. Immunoreactions in carcinomas with distant metastases (MI) were stronger than in M0 cases. However, this difference did not reach statistical significance. The presence of lymph node metastases did not correlate with pS2 expression. High expression of pS2 in T4 and T3 carcinomas together with the finding of pronounced expression of the antigen at invasion fronts in single cases could be interpreted as a function in tumor cell invasion and motility. However, in metastases and recurrent tumors, pS2 expression did not differ from primary lesions (53% positive lesions). All in all, under consideration of the latter finding in particular and together with the randomly distributed immunopositive tumor cells and cell clusters in the majority of cases, it is more likely that the expression pattern of pS2 in colorectal carcinomas is a result of overall tumor cell heterogeneity.
A simple method of tumour culture.
Hood CJ. Parham DM.
Department of Histopathology, Royal Bournemouth Hospital, Dorset, U.K.
We describe a simple explant primary cell culture system which maintains the normal tumour stroma relationship. This technique utilises conventional cell culture methods combined with the skills found in the histopathological laboratory. This produces sections of tumour visible by light microscopy. Using this method we were able to maintain for up to 7 days good morphological preservation and demonstrated continued proliferation. This technique produces histological sections of tumour following in vitro culture that can be utilised for other molecular studies, e.g. immunohistochemistry and in situ PCR. This method should prove invaluable to pathologists enabling direct visualisation and localisation of molecular events involved in tumour growth.
Subtotal liver calcification due to epithelioid hemangioendothelioma.
den Bakker MA. den Bakker AJ. Beenen R. Mulder AH. Eulderink F.
Department of Pathology, Reinier de Graaf Gasthuis/SSDZ, Delft, The Netherlands. email@example.com
A hepatic epithelioid hemangioendothelioma leading to almost complete calcification of the right and left liver lobes in a 75-year-old female is reported. Over a period of 16 years the liver progressively calcified, but its function remained normal by compensatory hypertrophy of the caudate lobe. Multiple partially calcified metastases were present in the lungs, peripancreatic region and along the left principal bronchus. Extreme liver calcification has only rarely been reported. The case presented here reflected slow tumor growth and subsequent long disease course. The vascular nature of the tumor was confirmed by immunohistochemical and ultrastructural analysis.
Signet-ring cell aggregates simulating carcinoma in colon and gallbladder mucosa.
Michal M. Chlumska A. Mukensnabl P.
Medical Faculty, Charles University Pilsen, Czech Republic. firstname.lastname@example.org
We describe three cases of benign signet-ring cell aggregates in the colon associated with pseudomembranous colitis, adenomatous polyp of the colon and ulcerated mucosa of the gallbladder excised for gallstones. In all cases, we found loose, benign signet-ring cell aggregates overlying the ulcerated mucosa surface, simulating signet ring-cell carcinoma. The most important sign of the benign signet-ring cell aggregates is that they are always confined to the surface of the mucosa of the intestine or gallbladder mucosa or crypts of the intestinal epithelium. In no case did we see an invasion of these cells into the lamina propria of the mucosa. In all cases, the benign signet-ring cell aggregates were immunohistochemically positive with antibodies to cytokeratins. The occurrence of benign signet-ring cell aggregates is a rare and very misleading diagnostic pitfall which must be differentiated from signet-ring cell carcinoma of the colon and gallbladder.