BACKGROUND: 8-Hydroxydeoxyguanosine (8-oxodG) is the commonly used marker of oxidative stress-derived DNA damage. 8-OxodG formation is regulated by local antioxidant capacity and DNA repair enzyme activity. Earlier studies have reported contradictory data on the function of 8-oxodG as a prognostic factor in different cancer types. METHODS: We assessed pre-operative serum 8-oxodG levels with an enzyme-linked immunosorbent assay in a well-defined series of 173 breast cancer patients. 8-OxodG expression in the nuclei of cancer cells from 150 of these patients was examined by immunohistochemistry. RESULTS: The serum 8-oxodG levels and immunohistochemical 8-oxodG expression were in concordance with each other (P
Increased synthesis and degradation of extracellular matrix components are associated with breast cancer development. This study evaluated type I and type III procollagen mRNA expression and the corresponding protein synthesis and maturation, as well as the tissue distribution of these collagens, in benign breast lesions, infiltrating ductal carcinomas, and their metastases by in situ hybridization and immunohistochemistry. In the benign lesions, the type I and type III collagen bundles were regularly organized and the expression of the corresponding mRNA was weak, indicating a relatively slow collagen turnover. In the malignant tumours, increased expression of type I and type III procollagen mRNAs was observed in the fibroblastic cells of the stroma; the malignant epithelial cells did not participate. The staining of corresponding newly-synthesized pN-collagens showed aberrant bundles in the invasive front of the malignant tumours. Newly-synthesized type I and type III procollagens were occasionally observed in fibroblastic cells, particularly in grade 2 and grade 3 tumours. Metastases of breast carcinoma resembled poorly differentiated primary tumours with respect to their collagen synthesis and deposition. The increased synthesis of fibrillar type I and type III procollagens may serve as a pathway for tumour invasion. The enhanced synthesis is associated with the formation of aberrant collagen bundles, which may be more readily degradable and may thus facilitate breast tumour invasion.
The majority of oral squamous cell carcinomas (OSCCs) are preceded by visible changes in the oral mucosa, most often white patches. Although the histological finding of dysplasia in oral white patches signals increased risk of developing OSCC, this may also occur in non-dysplastic lesions. However, no reliable markers exist to predict the occurrence of OSCC in these patients. From a total of 263 patients diagnosed with oral white patches, biopsies from 45 patients were selected on the criteria that the patients had lesions histologically proven to be non-dysplastic. The lesions were analyzed with respect to their DNA content. The clinical outcome of the patients was known from the Cancer Registry of Norway, and these data were compared to the DNA content of their lesions. Among the 45 patients, five cases (11%) later developed an OSCC. Four of the cases that subsequently developed an OSCC were among the five aneuploid (abnormal) cases (P=0.001). One aneuploid lesion did not develop a carcinoma during a follow-up time of 120 months. The fifth case that subsequently developed an OSCC was diploid (normal), and developed into an OSCC after an observation time of 73 months (P=0.001). In conclusion, aberrant DNA content reliably predicts the occurrence of OSCC in patients that otherwise would be regarded as at very low risk. Normal DNA content indicates low risk.
To test whether academic centers (ACs) are more successful than nonacademic centers (NACs) in immunohistochemistry (IHC) external quality assessment challenges in the Canadian Immunohistochemistry Quality Control (CIQC) program.
Results of 9 CIQC challenges for breast cancer marker (BM) and various non-breast cancer marker (NBM) tests were examined. Success rates were compared between AC/NAC laboratories and those located in small or large cities. Performance was also correlated with annual IHC case volumes.
There was no statistically significant difference in performance in any of the comparisons. However, overall performance on BM was significantly better (P
BACKGROUND/AIMS: Adenomas develop only rarely in the small bowel mucosa. We particularly tried to clarify the histologic change in atypia of ampullary adenomas which are not familial polyposis. METHODOLOGY: Four adenomas, 4 adenocarcinomas, and 4 normal mucosal regions of the ampulla of Vater were investigated in this study. All cases were characterized in paraffin sections for the presence of p53 protein using the anti-p53 monoclonal antibody (DO7, Dako Corp., Glostrup, Denmark) and proliferating cell nuclear antigen using the anti-PCNA antibody (PC 10, Dako A/S, Copenhagen, Denmark). To obtain the percentages (labeling index) of PCNA, a dual wavelength imaging microdensitometer (CAS 200, Elmhurst, IL) was used. RESULTS: Transition of adenoma into adenocarcinoma was recognized in 2 of 4 cases. Labeling index of PCNA was 12.2% in normal mucosa, 41.3% in adenomas, and 66.0% in adenocarcinoma, respectively. In 2 cases with carcinoma in adenoma, labeling index was higher in carcinomatous lesion than in adenomatous lesion. p53 Protein was positive in all cases of adenocarcinoma of the ampulla of Vater, and not in any case of normal mucosa or adenoma. CONCLUSIONS: The adenoma-carcinoma sequence was morphologically recognized especially in tiny carcinoma in adenoma of the papilla of Vater. Both p53 mutation and high proliferative activity play important roles for the histogenesis of invasive adenocarcinoma.
Capecitabine is an active agent in the treatment of breast cancer. It is not known whether integration of capecitabine into an adjuvant regimen that contains a taxane, an anthracycline, and cyclophosphamide improves outcome in early breast cancer.
Women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive either three cycles of docetaxel and capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX; n = 753) or three cycles of docetaxel (T) followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF; n = 747). The primary end point was recurrence-free survival (RFS).
During a median follow-up time of 59 months, 214 RFS events occurred (local or distant recurrences or deaths; TX/CEX, n = 96; T/CEF, n = 118). RFS was not significantly different between the groups (hazard ratio [HR], 0.79; 95% CI, 0.60 to 1.04; P = .087; 5-year RFS, 86.6% for TX/CEX v 84.1% for T/CEF). Fifty-six patients assigned to TX/CEX died during the follow-up compared with 75 of patients assigned to T/CEF (HR, 0.73; 95% CI, 0.52 to 1.04; P = .080). In exploratory analyses, TX/CEX improved breast cancer-specific survival (HR, 0.64; 95% CI, 0.44 to 0.95; P = .027) and RFS in women with triple-negative disease and in women who had more than three metastatic axillary lymph nodes at the time of diagnosis. We detected little severe late toxicity.
Integration of capecitabine into a regimen that contains docetaxel, epirubicin, and cyclophosphamide did not improve RFS significantly compared with a similar regimen without capecitabine.
Comment In: J Clin Oncol. 2012 Jan 1;30(1):1-222105825
Advanced glycation end products (AGE) accumulate in human tissue proteins during aging, particularly under hyperglycemia conditions. AGEs induce oxidative stress and inflammation via the receptor for AGEs (RAGE) and soluble RAGE (sRAGE) can neutralize the effects mediated by RAGE-ligand engagement.
We examined the association between N(e)-(carboxymethyl)lysine (CML), a prominent AGE, and sRAGE and colorectal cancer risk in a prospective case-cohort study nested within a cancer prevention trial among 29,133 Finnish male smokers. Among study subjects who were alive without cancer 5 years after baseline (1985-1988), we identified 483 incident colorectal cancer cases and randomly sampled 485 subcohort participants as the comparison group with the follow-up to April 2006. Baseline serum levels of CML-AGE, sRAGE, glucose and insulin were determined. Weighted Cox proportional hazard regression models were used to calculate relative risks (RR) and 95% CI.
Comparing highest with lowest quintile of sRAGE, the RR for incident colorectal cancer was 0.65 (95% CI, 0.39-1.07; P(trend) = 0.03), adjusting for age, years of smoking, body mass index, and CML-AGE. Further adjustment for serum glucose strengthened the association (RR = 0.52; 95% CI, 0.30-0.89; P(trend) = 0.009). Highest quintile of CML-AGE was not associated with an increased risk of colorectal cancer (multivariate RR = 1.20; 95% CI, 0.64-2.26).
Higher prediagnostic levels of serum sRAGE were associated with lower risk of colorectal cancer in male smokers.
This is the first epidemiologic study to implicate the receptor for AGEs in colorectal cancer development.
Cites: J Am Soc Nephrol. 2005 Aug;16(8):2363-7215930093
Cites: Ann N Y Acad Sci. 2005 Jun;1043:725-3316037299
Angiogenesis, the formation of new blood vessels, has been suggested to provide important prognostic information in prostate cancer. The aim of this study was to investigate, whether microvessel density (MVD) at diagnosis was correlated with disease-specific survival in a non-curative treated population of prostate cancer patients. MVD was immunohistochemically (factor VIII-related antigen) quantified in archival tumours obtained at diagnosis in 221 prostate cancer patients. The maximal MVD was quantified inside a 0.25 mm2 area of the tumour and the median MVD was 43 (range 16-151). MVD was statistically significantly correlated with clinicopathological characteristics and disease-specific survival. A multivariate analysis demonstrated that MVD was a significant predictor of disease-specific survival in the entire cancer population, as well as in the clinically localized cancer population. These findings suggest that quantitation of angiogenesis reflects the spontaneous clinical outcome of prostate cancer.
Among the differentiation-related changes in neuroblastoma are expressions of mdr-1 and bcl-2, which may be potentially related to the resistance to anticancer chemotherapy. In the present study, the authors performed an immunohistochemical analysis of mdr-1 and bcl-2 expressions in 30 neuroblastomas using monoclonal anti-P-glycoprotein(mdr-1 product) antibody and monoclonal anti-bcl-2 antibody to investigate the significance of their expression. The overall incidence of mdr-1 and bcl-2 expressions were 53.3% (16/30) and 93.3% (28/30), respectively. The expressions of mdr-1 and bcl-2 didn't seem to be related to the status of preoperative chemotherapy or stage of disease. The expression of mdr-1 was closely related to the differentiation of tumor cells (p
Reduced expression of components of the cell-cell adhesive cadherin-catenin complex has been related to the invasive phenotype in many malignancies, but the prognostic value of altered expression of its separate components varies in colon cancer. Our objective was evaluation of the cadherin-catenin complex, considered as a functional unit, in colon carcinomas and its relationship to patient outcome.
Tumours from 206 patients operated for colon adenocarcinoma were analysed using immunohistochemistry of E-cadherin, alpha, beta, and gamma-catenins, and p120ctn. The sum of proteins with altered membranous expression was calculated as an overall adhesion score (ranging from 0 to 5) for each patient. The results were correlated with patient outcome.
Of the tumours included in the analysis 0.5% had score 0, 4.9% had score 1, 13.6% had score 2, 31.6% had score 3, 33.0% had score 4, and 16.5% tumours had score 5. None of the proteins examined had individual, independent prognostic value. However, an increase in the number of proteins in the cadherin-catenin complex with altered expression was associated with an increased risk of cancer death (univariate P=0.002; multivariate P=0.007, HR 1.48, 95% CI 1.11-1.96).
An increase in the number of adhesion proteins with altered expression in the primary tumour is associated with increasingly impaired prognosis for patients operated for colon carcinoma. The results reveal that the entire cadherin-catenin complex should be evaluated when assessing its prognostic value in the disease.