Time to first recurrence, pattern of recurrence, and survival after recurrence in endometrial cancer according to the molecular classification.

OBJECTIVE: Despite its generally favorable prognosis at primary diagnosis, recurrence of endometrial cancer remains an important clinical challenge. The aim of this study was to analyze the value of molecular classification in recurrent endometrial cancer. METHODS: This study included patients with recurrent endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort) with molecular classification of the primary tumor. RESULTS: Out of 594 molecularly classified endometrial cancer patients, 101 patients experienced recurrence, consisting of 2 POLEmut, 33 MMRd, 30 p53abn, and 36 NSMP tumors. Mean age at recurrence was 71 years and mean follow-up was 54 months. Overall, median time to first recurrence was 16 months (95% CI 12-20); with the shortest median time in MMRd patients, with 13 months (95% CI 5-21). The pattern of recurrence was distinct among molecular subgroups: MMRd tumors experienced more locoregional, while p53abn cases showed more abdominal recurrences (P = .042). Median survival after recurrence was best for MMRd cases (43 months, 95% CI 11-76), compared to 39 months (95% CI 21-57) and 10 months (95% CI 7-13) for the NSMP and p53abn cases respectively (log-rank, P = .001). CONCLUSION: Molecular classification is a significant indicator of survival after recurrence in endometrial cancer patients, and patterns of recurrence differ by molecular subgroups. While MMRd endometrial cancer show more locoregional recurrence and the best survival rates after recurrence, p53abn patients experience abdominal recurrence more often and had the worst prognosis of all recurrent patients.

[Hereditary colorectal cancer : An update on genetics and entities in terms of differential diagnosis]. / Hereditäres Dickdarmkarzinom : Ein Update zu Genetik und Entitäten aus differenzialdiagnostischer Sicht.

The pathologist can contribute to recognizing hereditary causes of colorectal cancer via morphology. By identifying so-called index patients, it is possible to take preventive measures in affected families. The precise definition of the clinical presentation and the histopathological phenotype help to narrow the spectrum of expected genetic alterations. Novelties within Lynch syndrome include the recognition of EPCAM as a fifth gene locus, as well as the newly defined Lynch-like syndrome with evidence of somatic mismatch repair (MMR) mutations. With regard to polyposis-associated syndromes, the spectrum of polyps, whether serrated, hamartomatous or classic adenoma, is of crucial importance. The resulting differential diagnosis includes (attenuated) familial adenomatous polyposis ([a]FAP), MUTYH-associated polyposis (MAP), polymerase proofreading-associated polyposis (PPAP), phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS), Peutz-Jeghers syndrome and juvenile polyposis, each with a specific genetic background.

CD101 inhibits the expansion of colitogenic T cells.

CD101 exerts negative-costimulatory effects in vitro, but its function in vivo remains poorly defined. CD101 is abundantly expressed on lymphoid and myeloid cells in intestinal tissues, but absent from naïve splenic T cells. Here, we assessed the impact of CD101 on the course of inflammatory bowel disease (IBD). Using a T-cell transfer model of chronic colitis, we found that in recipients of naïve T cells from CD101(+/+) donors up to 30% of the recovered lymphocytes expressed CD101, correlating with an increased interleukin (IL)-2-mediated FoxP3 expression. Transfer of CD101(-/-) T cells caused more severe colitis and was associated with an expansion of IL-17-producing T cells and an enhanced expression of IL-2Rα/ß independently of FoxP3. The co-transfer of naïve and regulatory T cells (Treg) protected most effectively from colitis, when both donor and recipient mice expressed CD101. Although the expression of CD101 on T cells was sufficient for Treg-function and the inhibition of T-cell proliferation, sustained IL-10 production required additional CD101 expression by myeloid cells. Finally, in patients with IBD a reduced CD101 expression on peripheral and intestinal monocytes and CD4(+) T cells correlated with enhanced IL-17 production and disease activity. Thus, CD101 deficiency is a novel marker for progressive colitis and potential target for therapeutic intervention.

Multi-colour FISH in oesophageal adenocarcinoma-predictors of prognosis independent of stage and grade.

BACKGROUND: Oesophageal adenocarcinoma or Barrett's adenocarcinoma (EAC) is increasing in incidence and stratification of prognosis might improve disease management. Multi-colour fluorescence in situ hybridisation (FISH) investigating ERBB2, MYC, CDKN2A and ZNF217 has recently shown promising results for the diagnosis of dysplasia and cancer using cytological samples. METHODS: To identify markers of prognosis we targeted four selected gene loci using multi-colour FISH applied to a tissue microarray containing 130 EAC samples. Prognostic predictors (P1, P2, P3) based on genomic copy numbers of the four loci were statistically assessed to stratify patients according to overall survival in combination with clinical data. RESULTS: The best stratification into favourable and unfavourable prognoses was shown by P1, percentage of cells with less than two ZNF217 signals; P2, percentage of cells with fewer ERBB2- than ZNF217 signals; and P3, overall ratio of ERBB2-/ZNF217 signals. Median survival times for P1 were 32 vs 73 months, 28 vs 73 months for P2; and 27 vs 65 months for P3. Regarding each tumour grade P2 subdivided patients into distinct prognostic groups independently within each grade, with different median survival times of at least 35 months. CONCLUSIONS: Cell signal number of the ERBB2 and ZNF217 loci showed independence from tumour stage and differentiation grade. The prognostic value of multi-colour FISH-assays is applicable to EAC and is superior to single markers.

Gastrin mediated down regulation of ghrelin and its pathophysiological role in atrophic gastritis.

The gastric hormone ghrelin is known as an important factor for energy homeostasis, appetite regulation and control of body weight. So far, ghrelin has mainly been examined as a serological marker for gastrointestinal diseases, and only a few publications have highlighted its role in local effects like mucus secretion. Ghrelin can be regarded as a gastroprotective factor, but little is known about the distribution and activity of ghrelin cells in pathologically modified tissues. We aimed to examine the morphological changes in ghrelin expression under several inflammatory, metaplastic and carcinogenic conditions of the upper gastrointestinal tract. In particular, autoimmune gastritis showed interesting remodeling effects in terms of ghrelin expression within neuroendocrine cell hyperplasia by immunohistochemistry. Using confocal laser microscopy, the gastrin/cholecystokinin receptor (CCKB) could be detected on normal ghrelin cells as well as in autoimmune gastritis. Functionally, we found evidence for a physiological interaction between gastrin and ghrelin in a primary rodent cell culture model. Additionally, we gathered serological data from patients with different basic gastrin levels due to long-term autoimmune gastritis or short-term proton pump inhibitor treatment with slightly reactive plasma gastrin elevations. Total ghrelin plasma levels showed a significantly inverse correlation with gastrin under long-term conditions. Autoimmune gastritis as a relevant condition within gastric carcinogenesis therefore has two effects on ghrelin-positive cells due to hypergastrinemia. On the one hand, gastrin stimulates the proliferation of ghrelinpositive cells as integral part of neuroendocrine cell hyperplasia, while on the other hand, plasma ghrelin is reduced by gastrin and lost in pseudopyloric and intestinal metaplastic areas. Ghrelin is necessary for the maintenance of the mucosal barrier and might play a role in gastric carcinogenesis, if altered under these pre neoplastic conditions.

Plexiform angiomyxoid myofibroblastic tumour: differential diagnosis of gastrointestinal stromal tumour in the stomach.

Mesenchymal tumours other than gastrointestinal stromal tumours are rare in the stomach. Nevertheless it is important to incorporate them into the differential diagnosis. Plexiform angiomyxoid myofibroblastic tumour is a recently described new entity of a presumably benign mesenchymal gastric tumour. This report presents what is believed to be the third case of this tumour. The tumour is characterised by bland spindle cells in a plexiform pattern, a mucinous extracellular matrix and a network of thin blood vessels. These findings are completely in line with the two previous reported cases. There was a strong positivity for alpha-smooth muscle actin and a low proliferation index (<2%). The tumour had no C-KIT or CD34 expression and no mutation in the C-KIT and PDFGRalpha genes. Plexiform angiomyxoid myofibroblastic tumour may present a new mesenchymal tumour entity in the stomach.