Pericyte plasticity - comparative investigation of the angiogenic and multilineage potential of pericytes from different human tissues.

Pericyte recruitment is essential for the stability of newly formed vessels. It was also suggested that pericytes represent common ancestor cells giving rise to mesenchymal stem cells (MSCs) in the adult. Here, we systematically investigated pericytes and MSCs from different human tissues in terms of their angiogenic and multilineage differentiation potential in vitro in order to assess the suitability of the different cell types for the regeneration of vascularised tissues. Magnetic-activated cell sorting (MACS®) was used to enrich CD34-CD146+ pericytes from adipose tissue (AT) and bone marrow (BM). The multilineage potential of pericytes was assessed by testing their capability to differentiate towards osteogenic, adipogenic and chondrogenic lineage in vitro. Pericytes and endothelial cells were co-seeded on Matrigel™ and the formation of tube-like structures was examined to study the angiogenic potential of pericytes. MSCs from AT and BM were used as controls. CD34-CD146+ cells were successfully enriched from AT and BM. Only BM-derived cells exhibited trilineage differentiation potential. AT-derived cells displayed poor chondrogenic differentiation upon stimulation with transforming growth factor-ß1. Interestingly, osteogenic differentiation was more efficient in AT-PC and BM-PC compared to the respective full MSC population. Matrigel™ assays revealed that pericytes from all tissues integrated into tube-like structures. We show that MACS®-enriched pericytes from BM and AT have the potential to regenerate tissues of different mesenchymal lineages and support neovascularisation. MACS® represents a simple enrichment strategy of cells, which is of particular interest for clinical application. Finally, our results suggest that the regenerative potential of pericytes depends on their tissue origin, which is an important consideration for future studies.

Susceptibility of larval Aedes aegypti and Aedes albopictus (Diptera: Culicidae) to dengue virus.

Mosquitoes vertically transmit many arthropod borne viruses, and as a consequence arboviruses are often present within the larval environment. We tested the hypothesis that Aedes aegypti (L.) and Aedes albopictus (Skuse) larvae were susceptible to dengue virus through two infection methods: exposure to dengue in the larval growth environment via viral supernatant, and exposure to infected tissue culture along with viral supernatant. In addition to investigating for the first time the susceptibility of larval Ae. albopictus to dengue virus, we analyzed the infection rate and viral titer of infected pools of Ae. aegypti when exposed to multiple serotypes of dengue. We found that both Ae. aegypti and Ae. albopictus larvae were susceptible to the three dengue virus serotypes to which they were exposed regardless of the exposure method and that there were significant differences between the serotypes in infection titer and infection rate. The finding that larval Ae. aegypti and Ae. albopictus are susceptible to dengue indicates that dengue might be able to spread among larvae within the larval habitat potentially contributing to the persistence of dengue in the environment.

Fetal gastric and small intestine pattern of intestinal mucus antigens in human gastric carcinomas.

The present immunohistological study was performed to investigate the expression of intestinal mucus-associated antigens in the different histological types of gastric carcinoma according to the classification of Laurèn and the WHO classification. We used the following antigenic markers: M3, present in all the goblet cells of the whole small and large intestine; M3SI, expressed in all the goblet cells of the small intestine, but only in some of them of the large intestine; M3D, mainly produced in the upper small intestine; and M3C, specific for colonic mucus cells. All these antigens were found to be similarly expressed in both Laurèn's intestinal and diffuse types. Nevertheless, M3 and M3C appeared to be more largely produced in carcinomas showing well-differentiated cells (tubulopapillary, mucinous, and signet ring cells according to the WHO classification). Our results evidenced the occurrence of two main fetal antigenic patterns in gastric carcinomas, one of the gastric type (M3SI produced to a larger extent than M3 and M3C) and the other one of the small intestinal type (M3 and M3SI more largely expressed than M3C). On the basis of their similar antigenic pattern, the histogenesis of carcinomas showing the fetal small intestinal antigenic profile may be associated with intestinal metaplasia. On the other hand, carcinomas with the fetal gastric pattern may originate from undifferentiated stem cells of the gastric mucosa. Thus, such immunohistological studies could lead to a better understanding of the histogenesis of gastric carcinomas.

Abnormal pattern of mucus-associated M1 antigens in histologically normal mucosa adjacent to colonic adenocarcinomas.

Apparently normal mucosae adjacent to colon adenocarcinomas were studied by cutting strips of mucosa from the entire length of 120 surgical specimens (94 located on the distal colon and 26 on the proximal colon). These mucosae were coiled into "Swiss rolls." Their mucus alterations were mapped by immunoperoxidase using antibodies against M1 antigens, oncofetal markers associated with precancerous colonic mucosa. We demonstrated mucus modifications in patches of mucosa at a distance from frank tumors. The extent of these alterations was not related to invasion by the adjacent carcinoma according to Dukes' classification. However, these mucus modifications were more frequently observed on the distal than on the proximal side, were more often found adjacent to mucinous hyperplasia or adenoma, and were observed in 8 of 10 mucosae bearing metachronous or synchronous distal colonic adenocarcinomas. Our results suggest that the M1 modifications characterizing an early stage of carcinogenesis could have a putative prognostic value in estimating the risk for metachronous distal colonic adenocarcinomas.

Monoclonal antibodies against oncofetal mucin M1 antigens associated with precancerous colonic mucosae.

We obtained seven monoclonal antibodies (MAb) against a gastric mucin of an ALeb patient. By immunoperoxidase on normal gastric mucosae, two MAbs (3-3A and 2-25 LE) reacted exclusively with the A and Lewis-positive individuals, respectively; the five other MAbs (1-13 M1, 2-11 M1, 2-12 M1, 9-13 M1, and 58 M1) stained the mucus cells of surface gastric epithelium independently of ABO or Lewis status. They did not stain normal colonic mucosae, but did stain fetal and precancerous colonic mucosae. Using serial sections, each anti-M1 MAb stained the same goblet cells in fetal and precancerous colon. Extensive search of other normal tissues showed that M1 antigens were restricted to the epithelium embryologically derived from the foregut (gastric and bronchial epithelium) and from Müllerian ducts (mucus cells of endocervix and prostatic utriculus). Some differences in the reactivities of the various anti-M1 MAb were observed in subesophageal, subtracheal, and endocervical mucus cells, suggesting that each anti-M1 MAb characterized a different M1 epitope. A mixture of these five anti-M1 MAbs allowed the estimation of M1 mucus modification in the precancerous colonic mucosae with a sensitivity near to that obtained with polyclonal anti-M1 antibodies. Papain and mercaptoethanol treatments destroyed the M1 epitopes, at variance with the A- or Lewis-related antigens. Our results therefore suggest that the expression of M1 epitopes in precancerous colonic mucosae cannot be due exclusively to alterations in mucin glycosylation but may be related to the reexpression of antigens associated with native gastric mucin which is normally produced by the fetal colon during the sixth month of gestation.

Early oncofetal antigenic modifications during rat colonic carcinogenesis.

M1 antigens, associated with adult rat surface gastric epithelium and which are present in fetal but not adult distal colon, were investigated in this colonic mucosa during carcinogenesis. Fifty Wistar rats were given s.c. injections of 1,2-dimethylhydrazine for 28 weeks. Using an immunohistochemical method, M1 antigens associated with goblet cells were shown to be present after 2 weeks of 1,2-dimethylhydrazine treatment in histologically normal mucosa and then in 78% of mucinous hyperplasia and polypoid-like glands, in 54% of hyposecreting glands, in 58% of dysplasias, Grades 1 and 2, in two of 12 dysplasias, Grade 3, and in five of five transitional mucosas adjacent to carcinoma. The production of sialomucins associated with M1 antigens was often seen in the same histological lesion, although not always associated in the same goblet cells. The number of these histological lesions as well as the production of M1 antigens increased with the number of injections. Thus, these antigenic changes of an oncofetal nature can be regarded as early transformations of goblet cell differentiation in colonic mucosa subjected to chemical carcinogen.

A new mucin-associated oncofetal antigen, a marker of early carcinogenesis in rat colon.

We report the characterization of an IgG2a monoclonal antibody, (MAb) 660, prepared against rat gastric high molecular weight glycoproteins. By immunoperoxidase staining, MAb 660 reacted only with the mucous cells of surface gastric epithelium and with a few duodenal goblet cells close to the pylorus in normal adult rats. In fetuses, it reacted with intestinal and colonic goblet cells. The adult colon was always negative. The MAb 660 stained 100% (30 of 30) of chemically induced colonic carcinomas and 100% (7 of 7) of duodenal carcinomas. Several weeks before the appearance of tumors, histologically normal glands, then hyperplasia and dysplasia were precociously stained with MAb 660. The tissue distribution was different from that of blood group related antigens and M1 fucomucins. The recognized antigen was not sensitive to neuraminidase treatment. After electrophoresis in polyacrylamide gel, staining with periodic acid-Schiff reagent and Western blotting showed that the MAb 660 recognized an epitope associated with high molecular weight glycoproteins. This epitope was unaffected by beta-mercaptoethanol reduction-periodate treatment and neuraminidase and trypsin digestion. However, trypsin digestion performed after beta-mercaptoethanol reduction destroyed the 660 epitope. These data suggest that the antibody could recognize the peptide moiety of the mucin rather than its carbohydrate moiety. Thus, the new antigen identified by MAb 660 is a mucin-type glycoprotein with an oncofetal behavior in the rat colon and is precociously expressed by precancerous colonic mucosa.

Immunohistological study of precancerous mucus modification in human distal colonic polyps.

The M1 antigens associated with gastric fucomucins, oncofetal markers of the distal colonic mucosa, were demonstrated to be more closely associated with adenomas [92 of 139 (66%)] than with invasive adenocarcinomas [27 of 218 (12%)]. They were always expressed in tumors containing the M3 antigen normally associated with the intestinal mucus. The M1 antigens, present in 100% of hyperplastic polyps (30 of 30), were not specific for a particular histological type of adenoma but were found to be more closely associated with those showing a villous differentiation [41 of 47 (87%)] than with those having a tubular pattern [51 of 92 (55%)]. The presence of these M1 antigens depended neither on the size nor on the degree of cytological atypia of the nodular adenomas. However, M1 antigens were found in 94% of the adenomas (35 of 37) concomitant with adenocarcinomas; in contrast, only 56% of adenomas (55 of 102) observed on noncancerous mucosa contained these M1 antigens. As already demonstrated during rat colonic carcinogenesis, mucus modification characterized by the presence of M1 antigens could represent early molecular changes occurring before malignant transformation related to a chemical carcinogen. These M1 antigens might be regarded as early precancerous markers of an oncofetal type, associated with human distal colonic mucosa.

Monoclonal antibody FW6 defines an epitope on alpha 3/4-monofucosylated polylactosaminoglycans expressed by fetal and colon carcinoma-associated mucins.

A mouse IgM monoclonal antibody FW6 was established after immunization of mice with mucins from human amniotic fluid and was characterized with regard to its binding epitope. According to a series of biochemical criteria the epitope is located on O-linked neutral carbohydrates of M(r) 700,000 and M(r) 570,000 mucins in human amniotic fluid. The epitope is presumed to contain alpha 3/4-linked fucose and terminal beta 3/4-linked galactose that are labile to the fucosidase I from almond emulsion or to the galactosidase from bovine testes, respectively. Immunoreactive fractions of glycan alditols from human amniotic fluid mucins were partially characterized by fast atom bombardment-mass spectrometry and methylation analysis to be composed of monofucosylated polylactosamine-type deca- or nonasaccharides. According to antibody competition studies, inhibition assays with defined carbohydrates and binding assays on neoglycolipids monoclonal antibody FW6 are presumed to recognize a novel epitope that is distinct from known carbohydrate markers of the Lex/Ley family associated with colonic carcinomas. The selective reactivity of this monoclonal antibody to the majority of human colonic carcinomas and its nonreactivity to normal colonic mucosa may render this antibody as a valuable tool in cancer diagnosis or cancer treatment.

Tk, a new colon tumor-associated antigen resulting from altered O-glycosylation.

Erythrocyte polyagglutination antigens T and Tn are truncated O-glycan chains that are also carcinoma-associated antigens. We investigated whether Tk polyagglutination antigen could similarly be a carcinoma-associated marker and a target of immunotherapy. Monoclonal antibody LM389 was raised against Tk erythrocytes and tested by immunohistochemistry. LM389 strongly reacted with 48% human colorectal carcinomas. Labeling of normal tissues was visible on epithelial cells, mainly digestive, but was confined at a supranuclear level. Expression of the antigen on cloned human carcinoma cells correlated with sialosyl-Tn expression. O-Sialoglycoprotein endopeptidase treatment revealed that on carcinomas and cell lines, the epitope was present on O-glycans. Antibody specificity was determined using synthetic carbohydrates. Direct binding and inhibition studies indicated that LM389 best ligands were terminated by two branched N-acetylglucosamine units. Screening of murine cellular cell lines with LM389 allowed development of an experimental model with Tk-positive and -negative cells in syngeneic BDIX rats. Vaccination of rats with Tk erythrocytes provided a protection against growth of rat Tk-positive, but not of Tk-negative, tumor cells in association with the development of antibodies. Taken together, the results indicate that Tk polyagglutination antigen is a new colorectal carcinoma-associated antigen, absent from the normal cell surface, resulting from alteration of O-glycans biosynthesis and with potential as a target of immunotherapy.

Prospective study of Lewis antigen alterations in the gastric precancerous process.

A prospective study with two gastric biopsies taken several years apart was carried out in 117 subjects with intestinal metaplasia who are of the Lewis(a-b+) phenotype. They are residents of a rural Andean region in Colombia displaying very high rates of gastric cancer. The anomalous expression of Lewis(a) antigens in the metaplastic epithelium carried a significantly increased risk of colonic metaplasia and dysplasia. Such risk was much higher when the simultaneous expression of sulfomucins and Lewis(a) antigen was observed.

Immunohistological characterization of mucin epitopes by pre-treatment of gastro-intestinal sections with periodic acid.

Periodate pretreatment of paraffin sections of ethanol-fixed gastrointestinal mucosae was used to characterize the carbohydrate or peptidic nature of mucin epitopes by immunoperoxidase. Immunoreactivity of monoclonal antibodies (MAbs) against histo-blood group related carbohydrate epitopes such as A, Lea, Lec, Sialosyl Lea, H type 2, I, T, Tn and sialosyl Tn dramatically decreased or even disappeared after periodate pretreatment of deparaffinized sections. In contrast, the immunoreactivity of MAbs against peptide mucin epitopes such as the gastric M1 mucin epitopes was almost unaffected by this treatment. Moreover, periodate treatment revealed cryptic peptide M1 mucin epitopes and the peptide MUSE11 epitope associated with the 20 amino acid tandem repeat (PDTRPAPGSTAPPAHGVTSA). An increase of cross-reactions of anti-human M1 MAbs with gastric epithelium of different vertebrate species was detected with periodate treatment. Our results suggest that this method can be useful for preliminary characterization of the biochemical nature of mucin epitopes (peptidic or saccharidic) and for demasking peptidic tumour markers which are hidden by saccharide molecules in normal tissues.

Intestinal metaplasia and carcinomas of the human stomach: an immunohistological study.

Rabbit immunization with duodenal or colonic high molecular weight components allowed us to distinguish three new M3 antigens associated with intestinal goblet cells; these were denoted as M3SI, M3D, and M3C. Using immunoperoxidase staining, the anti-M3SI serum labeled all goblet cells in the small intestine, and a certain number of them in the colon, mainly in its proximal part. The anti-M3D serum reacted primarily with the goblet cells of the duodenal villosities, and the anti-M3C serum with all goblet cells of the large, but not the small, intestine. Moreover, the M3C antigen was recovered in some goblet cells of the fetal duodenum, in association with the two other markers. Only the M3D and the M3SI antigens were observed in the normal duodenum and intestinal metaplasia (IM) of benign gastric mucosa. In contrast, IM adjacent to gastric carcinomas, whatever their histological type, contained the M3C antigen in addition to M3D and M3SI antigens, and thus showed an antigenic pattern similar to fetal duodenum. Some gastric carcinomas, especially those with intestinal-like differentiation, produced the colonic M3C antigen as the neighboring IM. Thus, these two tissues displayed common differentiation features, which could be related to fetal duodenum rather than to adult colon.

Expression of mucin peptide and blood group ABH- and Lewis-related carbohydrate antigens in normal human conjunctiva.

PURPOSE: The immunohistochemical characterization of mucin peptide antigens and identification of blood group ABH- and Lewis-related carbohydrate antigens expressed in epithelium of normal human conjunctiva. METHODS: Immunoperoxidase characterization of conjunctival glycoproteins was performed using antibodies against peptide and saccharide moieties of gastrointestinal mucins on conjunctival biopsy specimens from 89 healthy individuals of known ABO and Lewis red cell phenotypes. RESULTS: Ocular mucins had epitopes in common with the peptidic core of gastric mucin (M1 epitopes), but also contained sialylated saccharide chains like those of intestinal mucins. Anti-M1 gastric mucins, anti-type 1 precursor, and anti-T antibodies strongly stained the cytoplasm of goblet cells. Anti-Lea, anti-NeuAc-Lea, and anti-Leb antibodies stained both epithelial and goblet cells of Lewis-positive individuals only. Anti-H type 1, anti-H type 2, anti-A, and anti-B stained epithelial cells of ABH secretors. In addition, A-like epitopes independent of secretor phenotype were found in epithelial and goblet cells of all donors. CONCLUSIONS: The conjunctival mucins cross-react with antibodies specific for digestive mucins and for blood group-related carbohydrate epitopes. The distributions of Lewis and secretor phenotypes in conjunctiva are: 19% Lewis-positive nonsecretors, 71% Lewis-positive secretors, and 10% Lewis-negative secretors. Lea and Leb antigens are present on epithelial cells of Lewis-positive nonsecretors and Lewis-positive secretors, respectively, as expected for antigens under control of Lewis and secretor genes. The secretor alpha-2-fucosyltransferase is not expressed on goblet cells, as described for the goblet cells of the distal rectal colonic mucosae. ABH antigens synthesized by the products of A1, A2, B, and Se genes and modulated by the presence of the product of the Lewis gene are found in epithelial cells. In addition, A-related epitopes independent of the A1-A2 subtype, secretor, and Lewis phenotypes also are present in both epithelial and goblet cells.

Alteration of sialyl Lewis epitope expression in pterygium.

PURPOSE: Mucin-related antigens are abundantly expressed by the cells of the normal human conjunctiva. The pattern of these antigens in pterygium, and especially the role of Galbeta1-3GlcNAc alpha2,3-sialyltransferase (ST3Gal III), sialyltransferase necessary to build the sialyl-Le(a) (Lewis(a)) antigen, were studied. METHODS: Immunoperoxidase staining was performed on 28 pterygia using different monoclonal antibodies: anti-M1 (against the peptidic core of gastric mucins encoded by MUC 5AC gene), anti-Le(a)(7LE), anti-sialyl Le(a)(NS 19-9), and anti-Le(b)(2-25LE). A serologic Lewis determination was done in 18 patients. ST3Gal III sialyltransferase expression was also studied in 10 healthy conjunctiva and 10 pterygia by reverse transcriptase-polymerase chain reaction (RT-PCR). Glyceraldehyde-3-phosphate-dehydrogenase was used as an endogenous internal control. RESULTS: First, Le(a), sialyl Le(a), and Le(b) immunoreactivities either decreased or were no longer detectable in pterygium goblet cells as opposed to normal conjunctiva. Second, unlike in pterygium, the Lewis immunoreactivity, which is mainly located in the surface epithelial cells in the normal conjunctiva, was occasionally restricted to the epithelial cells of the deep layers. However, M1 mucins did show an identical pattern expression in a normal conjunctiva and pterygium. ST3Gal III expression was significantly lower in pterygium (0.20+/-0.02 AU [arbitrary units]) than in normal conjunctiva (0.95+/-0.12 AU). CONCLUSIONS: ST3Gal III gene is less expressed in pterygium than in normal conjunctiva. This observation could explain the decrease of sialyl Le(a) expression observed in pterygium by immunohistology.

Gastric carcinoma with argyrophilic cells: light microscopic, electron microscopic, and immunochemical study.

An immunochemical study of a gastric adenocarcinoma with argyrophilic cells showed two areas of tumor that react differently with the usual histochemical reagents as well as with immune sera against gastrin and mucoprotein associated with antigens. Ninety per cent of the tumor cells were PAS positive and contained M2 antigen, and some also contained M1 antigen. About 30 per cent of the M2-positive cells stained strongly with an antigastrin serum as well as with the argyrophilic reagents. The remaining 10 per cent of tumor cells were signet-ring cells located in several clumps in the tumor. These cells were positive for both PAS and alcian blue and contained intestinal M3 antigen. Forty-five per cent of them also contained M1 gastric antigens. Carcinoembryonic antigen (CEA) was found in the cytoplasm of each tumor cell. The presence of CEA and M1 antigen together indicates a fetal pattern, suggesting that the cells originate from very immature gastrointestinal stem cells.

The foveolar cell component of gastric cancer.

M1, a mucin antigen, and cathepsin E, an aspartic proteinase, are both expressed in normal gastric superficial-foveolar epithelial cells. In this study, we determined by immunohistochemical staining the prevalence of these antigens in 316 gastric cancers representative of the main histologic types and stages of the disease. M1 was expressed in 201 cases (64%) and cathepsin E was expressed in 235 cases (75%) of the 313 cases investigated. Both antigens were expressed more commonly in diffuse and mixed cancers than in glandular tumors. M1 was found in 64 of 83 (77%) diffuse cancers and in 48 of 59 (81%) mixed cancers, but in only 74 of 146 (51%) glandular cancers. For cathepsin E, the prevalence was 93% in diffuse cancer, 81% in mixed cancer, and 71% in the 143 glandular cancers examined. Among 25 mucoid tumors, 15 (60%) expressed M1 but only eight (32%) expressed cathepsin E. Overall, 262 (84%) of the tumors expressed at least one of these antigens and of these, 173 (66%) expressed both antigens. No significant difference in the prevalence of M1 or cathepsin E was found between early and advanced cancer or between metastatic and nonmetastatic cancer. The two markers differed in their intracellular localization. In superficial-foveolar cells, M1 immunostaining was concentrated in secretory granules, Golgi complex, and luminal mucous, whereas cathepsin E was found in the endoplasmic reticulum. Moreover, cathepsin E, but not M1, was found in the enterocytes of duodenal villi and, occasionally, in mucopeptic cells. Parallel histochemical and ultrastructural investigations confirmed the occurrence in gastric cancer of foveolar-type cells, manifested by periodic acid-Schiff- and/or alcian blue-reactive mucous granules having a punctate substructure. We conclude that superficial-foveolar cell differentiation is common in gastric cancer and is a major component of this type of tumor. However, pure foveolar cell differentiation is rare. Rather, most gastric cancers consist of cells exhibiting features of foveolar, intestinal, and mucopeptic cell lines.

Distribution of GICA in normal gastrointestinal and endocervical mucosae and in mucinous ovarian cysts using antibody NS 19-9.

Through the immunoperoxidase method using antibody 19-9, we demonstrated the presence of gastrointestinal cancer-associated antigen (GICA) in normal gastrointestinal and endocervical mucosae and in benign mucinous ovarian cysts of pure endocervical type in Le(a+b-) and Le(a-b+) patients exclusively. However, GICA was more quantitatively expressed in Le(a+b-) than in Le(a-b+) patients. GICA was always encountered in the ducts of esophageal glands, Wirsung's ducts, goblet cells of villosities near the ileo-colonic junction, and the mucus columnar cells of the endocervical mucosae or ovarian mucinous tumor epithelium. In other areas of the gastrointestinal tract, GICA was sometimes found in the mucus cells of esophageal glands, near the neck cells of gastric mucosae, in goblet cells of the upper part of the small intestinal villosities, and in colonic Lieberkühn glands, especially in the cell maturation compartment. GICA therefore appears to be a normal component of gastrointestinal and endocervical mucosae.

Aneuploidy and expression of gastric-associated mucus antigens M1 and CEA in colorectal adenomas.

A series of 55 flow cytometric characterized colorectal adenomas was analyzed with four different monoclonal antibodies (Mabs) for the occurrence of M1 antigens (associated with gastric fucomucins) and one Mab for carcinoembryonic antigen (CEA). The antigens were detected with an indirect immunoperoxidase technic on paraffin sections after pretreatment with pronase for M1 antigens and without pretreatment for CEA. The staining pattern revealed different correlations with the various parameters, i.e., size, histologic type, atypia, and ploidy of the adenomas. Especially the cytoplasmic staining of anti-M1, Mab (1-13 M1) correlated well with aneuploidy (R = 0.43; P less than or equal to 0.001) and with the DNA index (R = 0.34; P less than or equal to 0.01). Staining of the anti-CEA Mab only correlated with the size of the adenomas (R = 0.29; P less than or equal to 0.03). It is concluded that the immunoreactivity of Mab (1-13 M1), which significantly correlated with aneuploidy, may be associated with malignant transformation in the adenoma-carcinoma sequence.

Early precancerous modifications in the mucus of human and rat distal colon: a comparative immunohistologic study.

The M1 antigens, associated with gastric fucomucin, the early oncofetal precancerous marker for the distal colon, were studied using the immunoperoxidase method in the distal colon. We compared human tumoral mucosa with that of rats during DMH-induced carcinogenesis. In both cases we examined histologically normal mucosa, mucinous hyperplasia, glands with serrated epithelium and hypermature goblet cells like those observed in human hyperplastic polyps, dysplasia, and transitional mucosa. We were able to assess similarities between these rat and human mucosae in terms of the tissue and cell location of these M1 antigens as well as the frequency of occurrence in the different comparative lesions. Thus, we demonstrated that such similarities can be observed not only at a histologic level, but also on a molecular level. The presence of M1 antigens in the human distal colon is comparable to mucous modifications induced by a chemical carcinogen, as observed during DMH-induced carcinogenesis in the rat.