A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms.

BACKGROUND & AIMS: Numerous gastrointestinal tumors, notably sporadic and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias, gastric cancers, and esophageal carcinomas, manifest microsatellite instability. Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability. One hundred thirty-eight human neoplasms (61 UC-associated, 35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this TGF-beta 1RII mutation. METHODS: Whether instability was present at other chromosomal loci in these lesions was determined. In lesions manifesting or lacking instability, the TGF-beta 1RII coding region polydeoxyadenine (poly A) microsatellite tract was polymerase chain reaction amplified with 32P-labeled deoxycytidine triphosphate. Polymerase chain reaction products were electrophoresed on denaturing gels and exposed to radiographic film. RESULTS: Three of 18 UC specimens with instability at other chromosomal loci (17%) showed TGF-beta 1RII poly A tract mutation, including 2 cancers and 1 dysplasia; moreover, 2% of UC specimens without instability (1 of 43) (1 cancer), 81% of unstable sporadic colorectal cancers (13 of 16), and none of the 61 stable or unstable gastric or esophageal cancers contained TGF-beta 1RII mutations. CONCLUSIONS: Mutational inactivation of the poly A microsatellite tract within TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonly in sporadic colorectal cancers but may be rare in unstable gastric and esophageal tumors.

Infrequent DPC4 gene mutation in esophageal cancer, gastric cancer and ulcerative colitis-associated neoplasms.

Homozygously Deleted in Pancreatic Cancer 4 (DPC4), a recently identified candidate tumor suppressor gene, was previously shown to be altered in human pancreatic cancers. We examined DPC4 mutation in 30 examples of three other types of gastrointestinal malignancy: 10 esophageal cancers, 10 gastric cancers and 10 colorectal cancers occurring in the preneoplastic condition, ulcerative colitis. The entire coding region of DPC4 (including all 11 exons) was analysed by either direct sequencing of PCR product or the in vitro synthesized protein assay. No coding region mutations of DPC4 were found in any of the samples examined. Our results suggest that inactivation of DPC4 may not be important in the majority of these types of gastrointestinal cancer.

[Are lymphocytic and collagenous colitis two forms of a single disease? Arguments taken from a biopsy quantitative study]. / La colite lymphocytaire et la colite collagène sont-elles une seule et même maladie? Arguments tirés d'une étude quantitative sur biopsie.

Collagenous colitis and lymphocytic colitis are defined by a clinicopathologic syndrome with chronic watery diarrhea, microscopic lesions of colonic biopsies, and normal barium enema and colonoscopy. A histopathological study was performed on multiple colorectal biopsies to compare 12 cases of collagenous colitis (defined by a subepithelial collagen thicker than 10 microns) and 7 cases of lymphocytic colitis (defined by a number of intraepithelial lymphocytes more than 20 per 100 epithelial cells at least in one biopsied site). The study included a semiquantitative analysis of inflammatory infiltrate in the lamina propria, crypts distortion and epithelial detachment. The number of intraepithelial lymphocytes per 100 epithelial cells was determined in surface epithelium and crypts. The subepithelial collagen thickening was studied by computerised morphometry. The intraepithelial lymphocytes, villous atrophy and thickness of the subepithelial collagen were also determined in gastric and duodenal biopsies. In collagenous colitis, the subepithelial collagenous thickness ranged from 10 to 40 microns in the colon (median 20.99 microns). In 4 cases of collagenous colitis, no thickening of the collagen plate was seen in the rectum. We found constant epithelial detachment and mucosal distortion. In lymphocytic colitis, the thickness of the subepithelial collagen ranged from 6 to 10 microns in 4 cases and was less than 6 microns in 3 cases (median 6.24 microns). The median number of intraepithelial lymphocytes in surface epithelium was 22.35 (range 18.2 to 40) in lymphocytic colitis versus 12.22 (range 4.6 to 24.4) in collagenous colitis. In conclusion, we observed an overlap of both the collagenous plate thickness and the number of intraepithelial lymphocytes in collagenous colitis and lymphocytic colitis. This result favours a unified histogenesis for these two entities.

Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms.

BACKGROUND & AIMS: Gastric cancers, sporadic colorectal cancers, and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias manifest microsatellite instability (MI); however, esophageal carcinomas rarely exhibit MI. Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in primary colorectal carcinomas demonstrating MI. No previous studies of TGF-beta 1RII have addressed mechanisms of inactivation other than MI in human tumors; furthermore, MI-negative tumors have not been examined for TGF-beta 1RII mutation. We evaluated 138 primary human neoplasms for mutation in the poly-A microsatellite tract of TGF-beta 1RII. Additionally, a group of esophageal tumors was evaluated for the expression of TGF-beta 1RII messenger RNA (mRNA). METHODS: First, we determined whether MI was present at other chromosomal loci in these lesions. The poly-deoxyadenine (poly-A) microsatellite tract within the TGF-beta 1RII coding region was then PCR-amplified. In a group of MI-negative esophageal tumors, RT-PCR was performed to determine the expression of TGF-beta 1RII mRNA. RESULTS: Among 17 MI+ UC specimens, 3 (18%) demonstrated TGF-beta 1RII poly-A tract mutation (2 cancers and 1 dysplasia), while 2 (4%) of 44 MI-negative UC specimens (1 dysplasia and 1 tumor), and 13 (81%) of 16 MI+ sporadic colorectal cancers, contained TGF-beta 1RII poly-A mutation. No gastric or esophageal tumors contained TGF-beta 1RII mutation. Among 21 MI-negative esophageal carcinomas. 6 cases (28.5%) had TGF-beta 1RII transcripts that were low or undetectable by RT-PCR. CONCLUSIONS: Mutation within the poly-A microsatellite tract of TGF-beta 1RII occurs early in a subset of UC-neoplasms and commonly in sporadic colorectal cancers, but may be rare in MI+ gastric tumors. Diminished expression of TGF-beta 1RII mRNA in esophageal tumors suggests that mechanisms of inactivation in this gene other than MI play a role in esophageal carcinogenesis.

Adenomatous polyposis coli gene mutations in ulcerative colitis-associated dysplasias and cancers versus sporadic colon neoplasms.

Adenomatous polyposis coli (APC) gene mutations occur in most sporadic colonic adenomas and carcinomas. Precursor lesions of ulcerative colitis (UC)-associated colon carcinomas, although morphologically similar to sporadic adenomas, may be biologically distinct from them and are, in fact, managed differently. Since sporadic adenomas may also occur in UC, a method of discriminating between these forms of neoplasia could have clinical utility. We examined 33 patients with UC-associated dysplasias and cancers and 23 sporadic colon neoplasms in a side-by-side comparison for APC mutations. Codons 686-1693, containing 64% of all reported APC mutations (the mutation cluster region), were screened for truncating mutations using an in vitro synthesized protein assay. Two of thirty-three patients (6%) with UC-associated dysplasias and cancers had a total of three truncating APC mutations, all in frank carcinomas, while 17 of 23 (74%) with sporadic colonic neoplasms had mutations. DNA sequencing confirmed two mutations in codon 1460, replacing arginine with a stop codon, as well as one 2-base pair deletion, resulting in a frameshift and a stop at codon 1477. One specimen contained one each of these APC mutations. This apparent contrast in mutation rates at the mutation cluster region of APC is consistent with other biological characteristics separating sporadic colon neoplasms from UC-associated dysplasias and cancers. These data raise the possibility that nonadenomatous UC dysplasias may arise by a molecular pathway distinct from that prevailing in sporadic colon carcinogenesis, and they suggest a molecular assay to discriminate between sporadic adenomas and dysplasias occurring in UC.

[Esophageal anomalies developed from tracheobronchial remnants. Reports of two cases with delayed diagnosis in adults]. / Anomalies oesophagiennes développées sur reliquats trachéobronchiques. A propos de deux cas de diagnostic tardif chez l'adulte.

Congenital esophageal stenosis and bronchogenic cyst are secondary to the same dysembryoplastic disorder in spite of different clinical signs. These lesions are revealed during infancy, unusually during adult age. Dysphagia is the most common symptom. Our two cases highlight these topics. Imaging methods displayed, in case 1, a distal stenosis, associated with a proximal dilatation, in case 2, a benign independent mass, without connection with the respiratory tract. A chirurgical excision was carried out in the two cases and the post operative course was uncomplicated. Histologically the two resection specimens showed a respiratory mucosa trapping cartilaginous pieces.