Whilst individual planning of treatment and follow-up in every colorectal cancer case is an increasing demand, prognostic markers are needed for predicting cancer progression in the primary phase. We ...studied the effect of replication error (RER)-positivity on colorectal cancer progression by analysing 255 colorectal cancer specimens by polymerase chain reaction (PCR) and fragment analysis and correlating the results with the clinical and histological features of the tumour and with patient outcome. RER-positivity was detected in 12% (28/235) of cases. It was associated with proximal location of the tumour (P<0.001), poor differentiation (P=0.001) and large tumour size (P=0.009). The 5-year cumulative survival rate of the patients with RER-positive cancer of the proximal colon was markedly better (100%) than that of those with RER-negative proximal cancer (74%), whilst in cases of cancer of the distal colon or rectum, RER-positivity (21%) indicated poorer survival than RER-negativity (57%). Thus, it is suggested that RER-positivity has an opposite impact on cancer progression in cases of proximal and distal cancers. RER-positivity appears to indicate improved prognosis only in cases of proximally located cancer, in which it could accordingly be useful as a prognostic marker.
Adjuvant therapies are increasingly used in colorectal cancers for the prevention of recurrence. These therapies have side-effects and should, thus, be used only if really beneficial. However, the ...development of recurrence cannot be predicted reliably at the moment of diagnosis, and targeting of adjuvant therapies is thus based only on the primary stage of the cancer. Loss of heterozygosity (LOH) in the long arm of chromosome 18 is suggested to be related to poor survival and possibly to the development of metastases. We studied the value of LOH at 18q21 as a marker of colorectal cancer prognosis, association with clinicopathological variables, tumour recurrence and survival of the patients. Of the 255 patients studied, 195 were informative as regards LOH status when analysed in primary colorectal cancer specimens using the polymerase chain reaction (PCR) and fragment analysis. LOH at 18q21 was significantly associated with the development of recurrence (P = 0.01) and indicated poor survival in patients of Dukes' classes B and C, in which most recurrences (82%) occurred. An increased rate of tumour recurrence is the reason for poor survival among patients with LOH at 18q21 in primary cancer. These patients are a possible target group for recurrence-preventing adjuvant therapies.
Increasing evidence suggests that a substantial proportion of colorectal carcinomas develop without a preexisting polypoid adenomatous lesion, but it is difficult to detect the possible origin of ...advanced carcinomas. The purpose of this study was to test the validity and significance of a new histopathologic classification system based on the histologic analysis of the tumor edge.
One hundred eighty-six unselected cases of colorectal carcinoma were included. A new classification method to distinguish polypoid and nonpolypoid growth type was based on the presence or absence of elevation of tumor as compared with adjacent mucosa. Inter- and intraobserver agreement of classification was tested. Association with other clinicopathologic features including histopathologic characteristics of the tumors, presence or absence of lesional and concurrent adenoma, K-ras mutations, and prognosis was evaluated.
Classification could be made in 75% of the tumors, and 25% were unclassifiable, mostly due to absence of tumor margin in sections. Of the classifiable carcinomas, 45% were classified as polypoid, of which 52% had lesional adenoma. Nonpolypoid tumors formed 48% of classifiable cases, and only 2% had lesional adenoma. Features of both polypoid and nonpolypoid carcinomas were present in 7% of cases. Concurrent extralesional adenomas were found more frequently in association with polypoid carcinomas. K-ras mutations were more common in polypoid (43%) than in nonpolypoid tumors (8%; P = 0.018). Nonpolypoid carcinomas were significantly (P = 0.03) more aggressive than polypoid carcinoma, with 38% and 20% recurrence rates, respectively.
The authors' results indicate that advanced colorectal carcinomas can be classified according to growth pattern by observing the tumor edge. This classification has prognostic significance because nonpolypoid carcinomas appeared to have a worse prognosis than polypoid ones.
We analyzed clinicopathological variables, cell proliferation activity and genetic aberrations related to colorectal cancer in order to recognize clinically usable predictive markers of cancer ...recurrence.
A total of 111 patients radically operated upon because of primary colorectal cancer in 1986-1991 were studied. Loss of heterozygosity (LOH) at 18q21 and replication errors were studied by polymerase chain reaction and fragment analysis. Expression of p53 protein and that of Ki-67 were studied using immunohistochemical methods.
LOH at 18q21 was the only factor associated with recurrence (P = 0.03), and indicated a worse five-year cumulative survival rate (42%) than did LOH-negativity (72%) in cases of Dukes classes B and C. Expression of p53 protein indicated recurrence (P = 0.07), short disease-free time and poor survival (P = 0.03) in Dukes class A cases.
LOH at 18q21 appears useful in predicting recurrence and poor survival in cases of Dukes classes B and C, as does p53 expression in class A cases.
The Cretaceous-Paleogene mass extinction approximately 66 million years ago is conventionally thought to have been a turning point in mammalian evolution. Prior to that event and for the first ...two-thirds of their evolutionary history, mammals were mostly confined to roles as generalized, small-bodied, nocturnal insectivores, presumably under selection pressures from dinosaurs. Release from these pressures, by extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, triggered ecological diversification of mammals. Although recent individual fossil discoveries have shown that some mammalian lineages diversified ecologically during the Mesozoic era, comprehensive ecological analyses of mammalian groups crossing the Cretaceous-Paleogene boundary are lacking. Such analyses are needed because diversification analyses of living taxa allow only indirect inferences of past ecosystems. Here we show that in arguably the most evolutionarily successful clade of Mesozoic mammals, the Multituberculata, an adaptive radiation began at least 20 million years before the extinction of non-avian dinosaurs and continued across the Cretaceous-Paleogene boundary. Disparity in dental complexity, which relates to the range of diets, rose sharply in step with generic richness and disparity in body size. Moreover, maximum dental complexity and body size demonstrate an adaptive shift towards increased herbivory. This dietary expansion tracked the ecological rise of angiosperms and suggests that the resources that were available to multituberculates were relatively unaffected by the Cretaceous-Paleogene mass extinction. Taken together, our results indicate that mammals were able to take advantage of new ecological opportunities in the Mesozoic and that at least some of these opportunities persisted through the Cretaceous-Paleogene mass extinction. Similar broad-scale ecomorphological inventories of other radiations may help to constrain the possible causes of mass extinctions.
The study of mammalian evolution depends greatly on understanding the evolution of teeth and the relationship of tooth shape to diet. Links between gross tooth shape, function and diet have been ...proposed since antiquity, stretching from Aristotle to Cuvier, Owen and Osborn. So far, however, the possibilities for exhaustive, quantitative comparisons between greatly different tooth shapes have been limited. Cat teeth and mouse teeth, for example, are fundamentally distinct in shape and structure as a result of independent evolutionary change over tens of millions of years. There is difficulty in establishing homology between their tooth components or in summarizing their tooth shapes, yet both carnivorans and rodents possess a comparable spectrum of dietary specializations from animals to plants. Here we introduce homology-free techniques to measure the phenotypic complexity of the three-dimensional shape of tooth crowns. In our geographic information systems (GIS) analysis of 441 teeth from 81 species of carnivorans and rodents, we show that the surface complexity of tooth crowns directly reflects the foods they consume. Moreover, the absolute values of dental complexity for individual dietary classes correspond between carnivorans and rodents, illustrating a high-level similarity between overall tooth shapes despite a lack of low-level similarity of specific tooth components. These results suggest that scale-independent forces have determined the high-level dental shape in lineages that are widely divergent in size, ecology and life history. This link between diet and phenotype will be useful for inferring the ecology of extinct species and illustrates the potential of fast-throughput, high-level analysis of the phenotype.
Regulation of Mammalian Tooth Cusp Patterning by Ectodin Kassai, Yoshiaki; Munne, Pauliina; Hotta, Yuhei ...
Science (American Association for the Advancement of Science),
09/2005, Letnik:
309, Številka:
5743
Journal Article
Recenzirano
Mammalian tooth crowns have precise functional requirements but cannot be substantially remodeled after eruption. In developing teeth, epithelial signaling centers, the enamel knots, form at future ...cusp positions and are the first signs of cusp patterns that distinguish species. We report that ectodin, a secreted bone morphogenetic protein (BMP) inhibitor, is expressed as a "negative" image of mouse enamel knots. Furthermore, we show that ectodin-deficient mice have enlarged enamel knots, highly altered cusp patterns, and extra teeth. Unlike in normal teeth, excess BMP accelerates patterning in ectodin-deficient teeth. We propose that ectodin is critical for robust spatial delineation of enamel knots and cusps.
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