Mucin histochemistry of the anal canal epithelium. Studies of normal anal mucosa and mucosa adjacent to carcinoma

Summary The epithelial lining of the anal canal is of colo-rectal type in the upper part and squamous in the lower part, while the middle zone is called the anal transitional zone (ATZ). This zone is characterized by an epithelium which bears a resemblance to that of the anal glands and shows little mucus secretion. The histochemical properties of the mucins in the epithelium of 39 anal canals, resected for ano-rectal adenocarcinoma, basaloid carcinoma, squamous carcinoma and malignant melanoma were investigated. The study reveals that (1) the mucin composition of the ATZ epithelium corresponds to that of the anal glands, being characterized by a mixture of sulpho- and sialomucins with scarcity or absence ofO-acylated sialic acids; and (2) cases with carcinomas located near the dentate line show changes in the mucin composition of the adjoining anal canal epithelium, regardless of tumour type. In colo-rectal type mucosa, these mucins consist of increasing amounts of sialomucins with a predominance ofN-acyl derivatives, and in the anal could be detected in the ATZ epithelium. It is concluded that rectal and anal glands in the anal canal are exposed to stimuli which alter the normal process of glycoprotein synthesis and secretion. The changes seem to be secondary to tumour growth and independent of the histological type of tumour.     

An ultrastructural application of silver methenamine to the study of mucin changes in the colonic mucosa adjacent to and remote from carcinoma

Synopsis A periodic acid-chromic acid-silver methenamine technique for visualizing glycoproteins at the electron microscope level was applied to colonic mucosa taken from areas adjacent to and remote from carcinoma. Normal control mucosa was obtained by biopsy of patients with no known gastrointestinal disease. Non-oxidized control sections were run in parallel. Quantitative and qualitative differences in glycoproteins were detected in the muscosa adjacent to carcinoma (transitional mucosa, as we call it) as compared with the normal. Furthermore, the vesicles in both the intermediate and absorptive cells elaborate a glycoprotein product and it seems that a direct relationship exists between the increased vesiculation and the markedly developed fuzzy coat in the transitional mucosa. It is suggested that these findings may represent one of the features of an early stage of carcinogenesis. Histochemical and ultrastructural techniques of the kind used in this study may thus be of value in identifying or predicting malignancy in the colonic epithelium.     

Variations in sialomucins in the mucosa of the large intestine in malignancy: a quantimet and statistical analysis

Synopsis The periodate-borohydride/saponification/PAS (PB/KOH/PAS) method, for the identification of sialic acid derivatives, was used to investigate possible changes in human colonic epithelium associated with carcinogenesis. The material was obtained from specimens of the large intestine resected for carcinoma and compared with normal control mucosa from biopsies of patients with no known gastro-intestinal diseases, using a Quantimet Image Analyser Densitometer to measure these staining reactions. An ordination or segregation analysis of the results revealed a marked discrimination between tumours and the normal control mucosa, with the values for the transitional mucosa and mucosa remote from the tumour graded in between. Pairedt-tests also showed statistically significant differences between the various types of mucosa. The fact that changes in the staining densities of the sialic acid derivatives are observed in mucosa which is normal by conventional histological criteria raises the hypothesis that malignancy in the colonic epithelium is accompanied by modifications in the sialic acid composition of the mucus secretion. Thus the PB/KOH/PAS method may be of value in the early detection of cancer in colo-rectal biopsies.     

Endocrine cells in gastric carcinoma and adjacent mucosa. An immunohistochemical and ultrastructural study

Endocrine cells are often found in human gastric carcinoma and may be recognized by the immunoreactivity of their chromogranin A, peptides and biogenic amines content. Anti-chromogranin A was used to investigate the morphology of endocrine cells using light and electron microscope immunohistochemical techniques. The hormone content of endocrine cells was examined in both tumour tissue and tumour-adjacent mucosa. It was found that the endocrine cells in tumour tissue were malignant, often had amphocrine differentiation and did not resemble a normal cell type. The hormone content of endocrine cells in tumour tissue seldom corresponded to the hormonal content of endocrine cells in tumour-adjacent mucosa. In intestinal-type carcinoma and in some parts of diffuse-type gastric carcinomas, endocrine cell hyperplasia and an alteration of the differentiation in the tumour-adjacent mucosa were discovered. The distribution of endocrine cells in the tumour tissue was different in both types of gastric carcinoma. The results reported here suggest that endocrine cell differentiation of malignant endocrine cells in human gastric carcinoma develops in a different way from that of endocrine cells in tumour-adjacent mucosa, and as a result, diverse hormonal products may appear in tumour tissue.     

Contribution of the microflora to proteolysis in the human large intestine

Protease activities in human ileal effluent were approximately 20-fold greater than in normal faeces. Comparative studies with faeces from a person who did not have a pancreas suggested that a substantial proportion of the proteolytic activity in normal faeces was of bacterial origin. Thimerosal, iodoacetate, EDTA and cysteine significantly inhibited proteolysis in faeces, but not in small intestinal contents, showing that cysteine and metalloproteases were produced by bacteria in the large gut. These results, together with results from studies using p-nitroanilide substrates, demonstrated that faecal proteolysis was both qualitatively and quantitatively different from that in the small intestine. Studies with pure cultures of proteolytic gut bacteria indicated that the cell-bound proteases of Bacteroides fragilis-type organisms were likely to contribute significantly towards proteolytic activity associated with the washed cell fraction and washed particulate fraction of faeces. Extracellular proteases were formed by Streptococcus faecalis ST6, Propionibacterium acnes P6, Clostridium perfringens C16, Cl. bifermentans C21 and Cl. sporogenes C25. Inhibition results suggested that these bacteria, and similar organisms, may be partly responsible for the extracellular proteolytic activity found in the cell-free supernatant fraction of faeces.     

Contribution of the microflora to proteolysis in the human large intestine

Protease activities in human ileal effluent were approximately 20-fold greater than in normal faeces. Comparative studies with faeces from a person who did not have a pancreas suggested that a substantial proportion of the proteolytic activity in normal faeces was of bacterial origin. Thimerosal, iodoacetate, EDTA and cysteine significantly inhibited proteolysis in faeces, but not in small intestinal contents, showing that cysteine and metalloproteases were produced by bacteria in the large gut. These results, together with results from studies using p -nitroanilide substrates, demonstrated that faecal proteolysis was both qualitatively and quantitatively different from that in the small intestine. Studies with pure cultures of proteolytic gut bacteria indicated that the cell-bound proteases of Bacteroides fragilis -type organisms were likely to contribute significantly towards proteolytic activity associated with the washed cell fraction and washed particulate fraction of faeces. Extracellular proteases were formed by Streptococcus faecalis ST6, Propionibacterium acnes P6, Clostridium perfringens C16, Cl. bifermentans C21 and Cl. sporogenes C25. Inhibition results suggested that these bacteria, and similar organisms, may be partly responsible for the extracellular proteolytic activity found in the cell-free supernatant fraction of faeces.     

The immunohistochemical study of trophoblast beta 1-globulin expression in cancer and in the mucosa of the large intestine]

The expression of pregnancy-specific beta-1-globulin (SP1) was studied in cancer-affected and nonaffected colon mucosa. The antigen was revealed in 19 out of 50 (38%) cases of carcinoma and in 1 out of 4 cases of ulcerative colitis. SP1 was found neither in noncancer colon mucosa nor in transitional mucosa and adenomas. The antigen was detected in the epithelium and stromal macrophages of carcinoma. SP1-positive cells were located mainly in the sites of tumor invasion. The results allow considering SP1 the tumor marker suitable for immunohistochemical diagnosis of colon cancer.     

Eicosanoids and the large intestine

During the past three decades, many studies have been conducted to determine the precise role of eicosanoids in colorectal physiology and pathophysiology. This research has increased our understanding of bioactive lipid signaling, and may contribute to the development of more effective therapeutic modalities for digestive diseases in the future. The purpose of this report is to provide a brief overview of the role of eicosanoids in the colon and rectum. This information has been organized according to both functional and disease-related categories. The role of eicosanoids in colonic secretion, motility, inflammatory bowel disease, and colorectal neoplasia will be discussed.     

Endometriosis of the large intestine]

Two cases of large intestine endometriosis are presented. The disease was diagnosed during histological examination of samples taken during surgery. Clinically one case was diagnosed as Crohn's disease, while the second as cancer of the large intestine. The authors suggest, that an extent of surgery for, tumours of the large intestine should be carefully planned, specially if the tissue specimen was not examined histologically earlier.     

Ligament system of the large intestine

Unconstant ligaments of the large intestine perform the function of its additional fixation. Their number increases as the mobility of the large intestine intensifies. During operative interventions the ligaments of the large intestine should be preserved. If their cutting is necessary, they should be subsequently restored.