Enzyme patterns and flow cytometric DNA measurements in colorectal hyperplastic polyps and tubular adenomas less than five millimeters.

Glucose-6-phosphate dehydrogenase (G6PD) activity, lactate dehydrogenase (LD) activity, and cytometric flow measurement of nuclear size and cell cycle distributions were registered in biopsy specimens from adenomas and hyperplastic polyps less than 5 mm. The G6PD and LD activities in adenomas, 36.8 +/- 4 U/g protein and 1580 +/- 163 U/g, respectively, were significantly higher than in hyperplastic polyps, 17.9 +/- 2.6 U/g and 1080 +/- 107 U/g, or in normal mucosa, 14.7 +/- 0.8 U/g and 1174 +/- 56 U/g, respectively. G6PD activity was significantly higher in adenomas with moderate (44 +/- 5.8 U/g) than in those with mild (32 +/- 5.9 U/g) dysplasia, in contrast to LD. No difference in enzyme activity was observed between hyperplastic polyps and normal mucosa. The growth of adenomas and hyperplastic polyps was not significantly different during the 2 years of follow-up study before biopsy specimens were taken. Increased nuclear size, unrelated to grade of dysplasia, was registered in 12 of 20 adenomas, in 1 of 10 hyperplastic polyps, and in 2 of 42 specimens from normal mucosa. Adenomas and normal mucosa from individuals with adenomas showed a significantly increased number of cells in S-phase. The values were 10.2 +/- 3% and 8.8 +/- 4%, respectively. Normal control value was 6.8 +/- 2.2%. An increased number of cells in G2-phase was observed only in adenomas (6.9 +/- 2.7% compared with 4.9 +/- 1% in controls). None of the adenomas showed aneuploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mucin histochemical changes in various colo-rectal polyps in relation to carcinoma of the large bowel].

210 various colo-rectal polyps including 46 inflammatory polyps, 21 juvenile polyps, 9 hyperplastic polyps, 65 tubular adenomas, 51 familial polyps, 11 villous adenomas, 7 adenomatous polyps with focal cancer, and 14 carcinoma of the large bowel were investigated by HE,HID-AB,PAT-KOH-PAS staining in order to study the mucin changes of these lesions. N-acetylated and C7,C9 O-acetylated sialomucin were mainly obtained in those adenomas with moderate and severe dysplasia (55-64.3%) and the proportion was even higher in cases of villous adenomas, familial polyps, adenomas with focal cancer and advanced carcinoma. These mucins might be assumed as a criteria in representing malignant transformation.

Mucin profiles and potential for malignancy of human colorectal adenomatous polyps.

The mucin histochemical and histologic features of 166 colorectal adenomatous polyps from 124 patients were studied. A majority of the polyps (62%) had a tubular growth pattern whereas 38% showed villous growth. Severe dysplasia was more frequently found in the latter group. A significant correlation (r = 0.27, P less than 0.001) was found between the severity of dysplasia and the size of the polyps. Moreover, the ratio between goblet and columnar cells was also found to decrease (P less than 0.0001) with the severity of dysplasia. Independent of the mucin stain used (periodic acid-Schiff, alcian blue, and high-iron diamine stains), mucin reactive cells were found to be negatively correlated (-0.17 less than r less than -0.44, P less than 0.01) with severity of dysplasia, especially in the tubular adenomas. These findings suggest that evaluation of mucin stain, related to dysplasia, may contribute to the assessment of premalignant and early malignant changes in adenomas of the colon.

The possibility of nonpolypoid carcinogenesis in the large intestine as inferred from frequencies of DNA aneuploidy of polypoid and crater-shaped carcinomas.

DNA ploidy patterns were studied by cytofluorometry in 60 cases of crater-shaped invasive carcinoma and 30 cases of polypoid tumor (severe dysplasia or submucosally invasive carcinoma located in the pedunculated, semipedunculated, or sessile polyp) of the large intestine. The data were compared with 20 cases of intramucosal differentiated (or intestinal type) adenocarcinoma of the stomach, with special reference to their macroscopic shape and frequency of DNA aneuploidy. DNA aneuploidy was found in 77% of the crater-shaped carcinomas and in 17% of the polypoid tumors of the large intestine. The frequencies were significantly different and the frequency gap amounted to 60%. However, 18 of 20 (90%) gastric adenocarcinomas were nonpolypoid in shape, whereas two (10%) were polypoid. DNA aneuploidy was found in 50% of the gastric adenocarcinomas and 56% of the nonpolypoid gastric adenocarcinomas. This value did not differ from the values reported previously for the submucosally invasive and advanced crater-shaped intestinal type adenocarcinomas of the stomach. Biologic characteristics of adenocarcinomas of the large intestine can be compared with those of intestinal type adenocarcinomas of the stomach, because intestinal type gastric adenocarcinoma is surrounded mostly by intestinalized mucosa and considered to arise from the epithelium under induction or progression of intestinal differentiation. Therefore, we inferred that the frequency gap in DNA aneuploidy between the crater-shaped and polypoid tumors of the large intestine implies that in the large intestine approximately 60% of the crater-shaped invasive carcinomas develop from the small nonpolypoid carcinomas.

Lectin histochemistry in colorectal polyps.

Lectin histochemistry has permitted an assessment of the glycoconjugate expression in colorectal polyps (Table 8). The T-antigen, a cancer-associated antigen, is expressed in colorectal adenomatous polyps. The apparent expression of T-antigen is related to the methodology used for its detection. FITC-PNA does not bind to glycoconjugates in the normal colon, however it is a sensitive marker for glycoconjugates secreted by colorectal cancers. The binding of FITC-PNA in adenomatous polyps is related to size and histology. The use of biotinylated PNA (followed by avidin-biotin-peroxidase) or PNA:anti-PNA is a more sensitive technique, and the result is that binding may be seen in the normal colon as well as most neoplastic lesions. The use of polyclonal and monoclonal antibodies to the T-antigen are more specific than the PNA:anti-PNA technique. Binding of PAb and MAb anti-T-antigen to colorectal polyps is related to the size of the polyp for both probes, and binding is also related to the degree of dysplasia for the MAb. The future of this work may be directed at an attempt to determine whether a family of closely related antigens are expressed in colorectal neoplasia with varying degrees of affinity for different probes of the T-antigen.

Hyperplastic polyposis of the colorectum and adenocarcinoma in a 24-year-old man.

Hyperplastic polyps in the large intestine are considered common after the age of 40, devoid of neoplastic transformation capability, and have a well-defined histological picture. Nevertheless, there exists evidence that hyperplastic polyps can present with adenomatous areas, eventually leading to carcinoma. There has been a suggestion in certain cases that a transformational sequence might exist in the genesis of colorectal cancer: hyperplastic polyp-adenoma-adenocarcinoma. Adenocarcinoma resulting from a pure hyperplastic polyp has also been described. These data have generated reconsideration of the significance of hyperplastic polyps in relation to cancer. In this paper we present a 24-year-old man with adenocarcinoma of the colon who underwent a right hemicolectomy. Twenty-eight hyperplastic polyps were found in the surgical specimen. Two of these polyps had adenomatous areas. The patient died 18 months after the surgical resection.

Nuclear steroid receptors and dysplasia in adenomatous polyps of the colon as markers of high risk for malignant transformation.

To detect an early colon carcinoma in its stage of carcinoma in situ, colonoscopic examinations with removal of all adenomas of the left colon (particularly of the sigmoid tract and rectum), followed by histological and biochemical evaluations, have been performed on 30 patients. Two-thirds of the adenomas examined presented histological patterns of tubular, tubulovillous, and villous adenomas; those with moderate or severe dysplasia were at high risk of neoplastic transformation. Measurement of estradiol (ER) and progesterone (PR) receptors was performed in the cytosol and in the nuclei of solitary and multiple adenomas and in those with synchronous carcinomas using the dextran-coated-charcoal (DCC) method. Steroid receptors were usually found in the cytosol of the large polyps of male rather than female patients (46% vs 11%) and in the cytosol of the adenomas with moderate or severe dysplasia in male patients. Malignant lesions usually possessed both ER and PR in the cytosol and nuclear fraction. These findings led to hypothesize that patients with adenomas of the colorectal tract with moderate or severe dysplasia and nuclear steroid receptors should be considered at high risk for colon carcinoma and therefore need a special follow-up program.

[Determination of cyclic AMP and protein kinases in the diagnosis of colonic tumors]. / Opredelenie tsAMF i proteinkinaz v diagnostike opukholei tolstoi kishki.

The cAMP level and the activity of cAMP-dependent and independent protein kinases were measured in adenomatous polyps, villous polyps (premalignant condition) and adenocarcinomas. The cAMP concentration and ratio of cAMP level versus cAMP-independent casein kinase activity were significantly lower in adenocarcinomas compared to adenomatous polyps, thus permitting differentiation between benign and malignant lesions. The cAMP versus cAMP-dependent histone kinase level ratio was used as a test for differentiation between malignancies and premalignant condition. It was markedly lower in adenocarcinomas than in villous polyps.

Mucin abnormality of colonic mucosa in patients with familial polyposis coli. A new tool for early detection of the carrier?

Colonic mucosa in 62 patients with familial polyposis coli (FPC) was stained by a Periodic Acid-Thionin Schiff/Potassium Hydroxide/Periodic Acid-Schiff method in which the normal colonic mucosa usually stained red and carcinoma stained blue or purple. In FPC, 82.2 percent stained blue or purple, whereas 38.8 percent stained blue or purple in normal controls. The data suggest that sialomucin properties of the normal-appearing flat mucosa in FPC are different from those of the normal colon, and that this simple technique may be useful for the early detection of high-risk individuals in the FPC family.

Tissue CEA detection by immunoperoxidase (PAP) test in colorectal polyps: correlations with the degree of dysplasia.

We study the presence of Carcinoembryonic antigen (CEA) on 39 colorectal polyps by the immunoperoxidase technique. The histological examination demonstrated 15 tubular adenomas, one villous adenoma, two tubulo-villous adenomas, six tubular adenomas with slight dysplasia, one tubular adenoma with moderate dysplasia, four tubular adenomas with severe dysplasia, three tubulo-villous adenomas with severe dysplasia, five tubular adenomas with neoplastic degeneration, and two tubulo-villous adenomas with neoplastic degeneration. Twenty-eight of thirty-nine polyps (71.79%) showed a positive staining reaction for CEA. Regarding the intensity of the reaction (classified as absent or negative [-], slightly positive [+], and markedly positive [+ +]), 11/39 polyps presented a negative reaction (28.21%), 19/39 (48.71%) presented a slight reaction, and 10/39 polyps (25.64%) presented a marked reaction. Results demonstrated a higher intensity of the staining reaction in severely dysplastic polyps and in neoplastic degeneration. In conclusion, it is possible that the presence of CEA can be useful to show an initial cellular restlessness of certain polyps.

Bile acid receptors in colorectal cancer.

Bile acids are thought to be involved in both the aetiology and development of colorectal cancer. In this study the existence of specific bile acid receptor proteins has been postulated. A receptor assay which involved labelling with 14C-deoxycholic acid was performed as well as autoradiography using 3H-deoxycholic acid. In an initial study resected colorectal cancer and adjacent histologically normal colorectal mucosa from 39 patients were studied, as were samples of normal gastric mucosa, cancers and benign colorectal tumours. Specific receptors to deoxycholic acid were detected in 12 (30.8 per cent) of the colorectal cancers, but in only 1 (2.6 per cent) of the samples from normal colorectal mucosa (X2 = 11.16, P less than 0.005). No deoxycholic acid receptors were detected in any other tissue studied. Autoradiographs of colorectal cancers showed binding of 3H-deoxycholic acid in receptor-positive tumour tissue. These findings might provide some explanation for the evidence linking bile acids with the disease.

Tumour marker acquisition in the polyp-to-cancer sequence in the colon.

Sequential studies of 6 tumour markers in an adenomatous polyp which eventually metastesized as adenocarcinoma are described. The findings suggest that with the development of malignancy, clones of cells with an increasing number of markers are favoured for continued growth and that this probably represents progressive gene derepression.

[Microspectrophotometric study of the DNA content of the nucleus of cells from premalignant polyps and cancer of the rectum]. / Mikrospektrofotometricheskoe issledovanie soderzhaniia DNK v iadrakh kletok maligniziruiushchikhsia polipov i raka priamoi kishki.

38 adenomatous polyps, 42 villous polyps with varying degree of proliferation and epithelial dysplasia, 34 polyps with preinvasive cancer components and 44 polyps containing invasive cancer elements were examined microspectrophotometrically. The analysis established an increased level of epithelial cells with ploidy varying 3c-5c to be a characteristic feature of the initial stages of malignant transformation of rectal polyps. The invasive cancer had similar peculiarities.

Tissue bile acids in patients with colon cancer and colonic polyps.

The purpose of this study was to determine whether in man unusual types of concentrations or bile acids were present in colonic polyps, colon carcinomas, or the adjacent, apparently normal tissue. Methods for the determination of soluble and tissue-bound bile acids were validated. Of 14 polyps analyzed, eight contained detectable levels of bile acid, predominantly chenodeoxycholic acid; no lithocholic acid was observed in either the tissue-bound or soluble bile acid fractions. Bile acids were found in four of nine samples of colon carcinoma; in one tumor, tissue-bound lithocholic acid was present. Bile acids were similarly found in seven of 10 samples of normal bowel taken adjacent to the carcinoma. In the soluble bile acid fraction, cholic acid was more abundant than chenodeoxycholic acid. There was no correlation between tissue histology and bile acid composition or concentration. Under the conditions used, this study did not disclose a relationship between tissue bile acids and colorectal histology.

Immunohistochemical evaluation of carcinoembryonic antigen, secretory component, and epithelial IgA in tubular and villous large-bowel adenomas with different grades of dysplasia.

In a material of 513 consecutively collected large-bowel polyps, tubular and villous adenomas with corresponding histologic grades of epithelial dysplasia were selected. Fifty-two samples of the former and 27 of the latter category were evaluated semiquantitatively for immunohistochemical staining of the epithelial marker proteins carcinoembryonic antigen (CEA), secretory component (SC), and IgA. No consistent differences in the overall staining properties were found between the two types of tumours. In both categories the staining intensity for SC and epithelial IgA decreased with increasing degree of dysplasia, most strikingly so for IgA. This observation shows that the malignant alterations impair the capacity of the columnar epithelium to produce SC and to express it as a functional receptor mediating uptake of dimeric IgA. Thus, the absence of epithelial IgA in large-bowel adenomas may be a useful adjunct in grading of dysplasia. Conversely, the presence of CEA did not seem to be related to dysplastic alterations in the epithelium.