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PURPOSE: Adenomatous polyposis coli protein, glycogen synthetase kinase-3-beta, T cell transcription factor/lymphoid enhancer-binding factor, and beta-catenin modulate cell differentiation and proliferation via the expression of effector genes. It has recently been postulated that betacatenin is a potent oncogene of sporadic colorectal carcinogenesis and a prognostic tumor marker. Our aim was to investigate whether the nuclear overexpression of betacatenin, possibly caused by mutations in exon 3 of betacatenin (CTNNB1), is correlated with distant metastatic spread or disease-free survival in rectal carcinoma. METHODS: Immunohistochemical analysis was performed with an anti-beta-catenin-monoclonal antibody on paraffin sections of two groups of patients (n=2 × 77) with rectal carcinoma curatively treated by surgery alone. The patients selected were all free of local disease, to exclude surgical influence. Patient groups were matched for age, gender, International Union Against Cancer stage, and year of operation (1982 to 1991) and differed only in subsequent metachronous distant metastatic spread. Follow-up was prospective (median, 9.6 years). Three staining patterns were defined: membranous (normal), diffuse cytoplasmic (pathologic), and intense nuclear staining (pathologic). When intense nuclear staining was defined, the specimen was microdissected. Then, DNA was isolated, polymerase chain reaction-amplified, and sequenced to detect mutations in exon 3. RESULTS: Nuclear overexpression of beta-catenin correlated neither with distant metastatic spread (chisquared, 0.37;P=0.79) nor with disease-free survival (log-rank with trend,P=0.62). No mutations were found in the area of the serine/threonine-kinase glycogen synthetase kinase-3-beta-phosphorylation site in exon 3 (CTNNB1) of beta-catenin. CONCLUSION: Although beta-catenin seems to play an important role in early colorectal carcinogenesis, its value as a prognostic marker is questionable. It must be assumed that metastatic ability is determined by other factors than the disturbance of the beta-catenin T cell transcription factor/lymphoid enhancer-binding factor cascade and that other mechanisms might cause the observed nuclear translocation of beta-catenin.

PURPOSE: The aim of this study was to determine the value of DCC (deleted in colorectal cancer) protein for predicting metachronous distant metastases after curative surgery for rectal cancer. The DCC protein—for which a gene has been located on chromosome 18q—has recently been reported to have a prognostic value in colorectal cancer. This finding might have implications for treatment of International Union Against Cancer Stage II rectal carcinoma, in which distant metastases will develop in 14 percent of patients despite optimal surgery. METHODS: Paraffin-embedded tissues from 85 patients who developed distant metastases, but no local recurrence, after curative surgery for rectal cancer were matched with 85 samples from patients who remained disease-free. Matching criteria were tumor stage, age, gender, and date of surgery. Expression of DCC protein was assessed using immunohistochemistry. End points of follow-up were recurrence of disease and death. Mean follow-up was 9.6 years. No patient received either local or systemic adjuvant therapy. RESULTS: The DCC protein was found to be expressed in 64.9 percent of tumor samples. Nonexpression of DCC protein had an negative influence on survival (P=0.03). For all tumor stages together, sensitivity of the test for subsequent occurrence of distant metastases was 42 percent and specificity was 71 percent. In Stage II cancers, the positive predictive value was 19 percent, and the negative predictive value was 88 percent. CONCLUSIONS: Our results confirm that DCC protein is a useful prognostic marker in patients with rectal carcinomas, but the positive predictive value of DCC protein for occurrence of metachronous metastases does not appear to be sufficient to justify adjuvant therapeutic measures in Stage II rectal cancer.

PURPOSE Total mesorectal excision (TME) and other technical surgical factors reduce local recurrence rate in rectal cancer. Scientific evidence of the positive effect of optimal surgery on survival is locking. Whether a reduction in the incidence of distant metastases can be achieved with optimal surgery is uncertain. We examine the effects of the quality of surgery, as reflected by local recurrence rate, on survival and the incidence of initial distant metastases. PATIENTS AND METHODS Between 1974 and 1991, 1,581 consecutive patients who underwent curative resection (RO) for rectal carcinoma were monitored for recurrence and survival. TME was introduced in 1985. No patient received adjuvant radiotherapy or chemotherapy. The median follow-up time was greater than 13 years. RESULTS The local recurrence rate decreased from 39.4% to 9.8% during the study period (P < .0001). The observed 5-year survival rate improved from 50% to 71% (P < .0001). Three hundred six patients with local recurrence had a significantly lower observed 5-year survival rate (P < .0001). A total of 1,285 patients had no local recurrence, but 275 of them developed distant metastases (International Union Against Cancer [UICC] stage I, 8%; stage II, 16%; stage III, 40%). Better-quality surgery had no effect on the incidence of initial distant metastases, which remained constant (P = .44). CONCLUSION Quality of surgery is an independent prognostic factor for survival in rectal cancer, but has no influence on initial occurrence of distant metastases. Local recurrence cannot be considered an outcome criterion of adjuvant treatment without consideration of the surgeon as a risk factor.

Introduction Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old). However, more recently, it has been observed that younger patients (less than 40 years of age) are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda. Case presentation A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon. Conclusions Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the diagnosis of colorectal malignancy in young African patients.

This study was performed to define selection criteria for adjuvant therapy in rectal cancer.An immunohistochemical analysis using nine monoclonal antibodies against CEA, CD15s, CD44v6, DCC, E-cadherin, EGF-R, NM23, PAI-1, and P53 was performed on paraffin sections of two matched (age, gender, UICC stage [I-III], year of operation [1982-1991]) groups of patients (n = 2 x 64) with rectal carcinoma curatively treated by surgery alone. The two groups differed only with regard to metachronous distant metastatic spread. In order to exclude the influence of surgery, all patients had to meet the selection criterion "free of locoregional disease." Follow-up was prospective (median 80 months). Conventional staining procedures and immunohistochemical evaluation were used. Tumor grading and lymphatic and extramural venous invasion were also investigated. Analysis was performed with Fisher's exact test and Kaplan-Meier estimates of disease-free survival (log rank). The Cox model was used for multivariate analysis.In univariate analysis only grading (P0.001) and extramural venous invasion (P0.001) correlated significantly with metachronous metastases. In multivariate analysis, beside grading (P = 0.010) and extramural venous invasion (P = 0.011), CD15s (P = 0.042) was also of significance. All other immunohistochemical markers failed.The histopathological parameters grading and extramural venous invasion appear to be acceptable predictors of metachronous distant spread in curatively resected rectal cancer. In contrast to the immunohistochemical markers, grading seems to better reflect the individual tumor phenotype and its behavior.

Two selected groups of 77 patients each (matched for age, sex, UICC stage and year of surgery) were compared. All patients were curatively operated on for rectal cancer by surgery alone. All remained locally disease-free, differing only in distant metachronous metastatic spread. β-Catenin expression was investigated using immunohistochemical methods. Overexpression of nuclear β-catenin was not correlated with diseasefree survival or distant metachronous metastasis. Thus, this potential oncogen cannot be used as a prognostic marker in rectal cancer. Additionally, in four cases of intense nuclear staining, after DNA isolation and sequencing of exon 3, which encodes for the GSK-3β phosphorylation site, no mutations could be detected.

we select these patients, and which effect can be achieved? The MRC trialists present data showing an unacceptably low rate of curative resections and a high rate of residual tumour and local recurrences. The question is whether a more appropriate surgical approach would give more benefit to the patients than any preoperative radiotherapy can do. Any additional therapy for rectal cancer must be aiming for better results and a better quality of life by achieving fewer abdominoperineal excisions, lowering of local recurrence, and better survival rates. None of these is clearly proved in this study.