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ABSTRACT: Clinical staging and histological grading after surgery have been the "gold standard" for predicting prognosis and planning for adjuvant therapy of colorectal cancer (CRC). With the recent development of molecular markers, it has become possible to characterize tumors at the molecular level. This is important for stage II and III CRCs, in which clinicopathological features do not accurately predict heterogeneity, e.g., in their tumor response to adjuvant therapy. In the present study, archival samples from 141 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital (Finland) were used (as microarray blocks) to analyze MUC2 expression by immunohistochemistry. Altogether, 49.7 % of all tumors were positive for MUC2. There was no significant correlation between MUC2 expression and age (P < 0.499), tumor invasion (P < 0.127), tumor staging (P < 0.470), histological grade (P < 0.706), lymph node involvement (P < 0.854), or tumor metastasis (P < 0.586). However, loss of MUC2 expression was significantly associated with disease recurrence (P < 0.031), tumor localization (P < 0.048), and with borderline significance with gender (P < 0.085). In univariate (Kaplan-Meier) survival analysis, positive MUC2 significantly predicted longer disease-free survival (DFS) and disease-specific survival (DSS) as well. However, in multivariate (Cox) survival analysis, MUC2 lost its power as an independent predictor of DFS and DSS. Our results implicate the value of MUC2 expression in predicting disease recurrence and long-term survival in CRC.
Tumor Biology 11/2012; · 1.94 Impact Factor
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ABSTRACT: The traditional staging system is currently inadequate for identifying those patients with colorectal carcinoma (CRC) who carry a high risk for poor outcome. In this study, the expression of E-cadherin was evaluated in CRC to determine its correlation with clinico-pathological variables, and association with disease outcome in patients with long-term follow-up. The present series consisted of tissue samples obtained from 230 patients with stage I, II, III, or IV CRC treated during 1981-1990 at Turku University Hospital. Archival paraffin-embedded samples were used to build up tissue microarray blocks, and E-cadherin expression was assessed by immunohistochemistry using an automated staining system. Different grading systems were tested for expression of E-cadherin. Fifty-nine percent of all tumors were positive for E-Cadherin. There was no significant correlation between E-cadherin expression and gender (p < 0.83), localization (p < 0.45), tumor invasion (p < 0.32), or histologic grade (p < 0.41). However, loss of E-cadherin expression was significantly associated with older age (p < 0.03) and lymph node involvement (p < 0.02), and with borderline significance with advanced stage (p < 0.09) and tumor metastasis (p < 0.09). In univariate (Kaplan-Meier) survival analysis, positive E-cadherin significantly (p = 0.009) predicted longer disease-free survival (DFS), and the same was true with disease-specific survival (DSS) as well (p = 0.007). In multivariate (Cox) survival analysis, E-cadherin retained its significance as independent predictor of DFS (HR = 1.56; 95% CI 1.01-2.42, p = 0.043), but not DSS. A sub-group analysis revealed that E-cadherin expression also predicts DFS (p < 0.01) and DSS (p < 0.04) in stage II CRC. Our results implicate the usefulness of E-cadherin expression in predicting disease recurrence and long-term survival in CRC.
Apmis 07/2012; 120(7):539-48. · 1.99 Impact Factor
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ABSTRACT: The frequency of over-expression of human epidermal growth factor receptor-2 (HER-2) in bladder cancer is one of the highest among all human malignancies. This over-expression is thought to play a role in aberrant proliferation of cancer cells. Studies on HER-2 expression in bladder carcinoma have shown heterogeneous results.
The aim of the study was to evaluate the status of HER-2 protein expression in patients with invasive carcinomas of the urinary bladder as related to tumor grade and stage.
Archival samples from 39 patients (6 women, 33 males) with urinary bladder cancer were analyzed for HER-2 over-expression, using immunohistochemistry with the HercepTest.
HER-2 over-expression was observed in 23/39 tumors (59%) and was more frequent in high-grade than in low-grade carcinomas, but the difference was not statistically significant. A significant correlation was established between HER-2 over-expression and tumor stage (p=0.011). HER-2 expression was more frequent in transitional cell carcinomas (TCC) and adenocarcinomas (AC) as compared with squamous cell carcinoma (SCC). Patients' age and sex were not related to HER-2 over-expression.
Over-expression of HER-2 was frequent in carcinomas of the urinary bladder. Knowing the HER-2 status would be helpful in formulating a rational treatment strategy for patients with urinary bladder cancer.
Libyan Journal of Medicine 01/2012; 7. · 0.18 Impact Factor
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ABSTRACT: Among the patients with bladder cancer, a group is still at risk of disease recurrence, progression, and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial carcinoma and is a potential therapeutic target.
To quantify tumor angiogenesis in bladder cancer and determine whether it correlates with tumor stage and grade.
A series of 42 archival samples from carcinomas of the urinary bladder were graded, staged, and analyzed for microvessel density (MVD) by a double immunohistochemical technique using Factor VIII (FVIII) and CD31 antibodies. The correlation between MVD and histopathological grade and tumor stage was evaluated.
FVIII and CD31 immunoreactivity was observed in 100% of cases and more intensely with CD31. Significantly higher MVD was determined in invasive tumors than in superficial tumors (p<0.05). MVD increased with tumor grade and stage (p<0.05); MVD was not affected by age or sex of the patients.
These data demonstrate that MVD in bladder carcinoma correlates with the tumor grade and stage. Quantification of tumor angiogenesis may allow selection of the type of treatment for bladder cancer patients.
Libyan Journal of Medicine 01/2011; 6. · 0.18 Impact Factor
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ABSTRACT: Ezrin is a membrane-cytoskeleton anchor, which, in experimental models, regulates tumor cell invasion and metastatic ability. We carried out immunohistochemical analysis of ezrin in 74 advanced colorectal cancer patients and correlated it to clinicopathologic variables and disease outcome. In contrast to the predominantly membraneous immunoreactivity of normal colorectal epithelium, ezrin expression in the colorectal cells was typically cytoplasmic. Altogether, 16.2% (12/74) of the tumors showed negative/weak ezrin staining, 35.1% (26/74) had moderate staining, and 48.6% (36/74) had intense staining. The expression was more intense in colon than in rectal carcinomas (P = .003). Increased ezrin expression was associated with adverse outcome, that is, shorter disease-specific survival; 48.3 months and 36.6 months for negative-weak versus intense expression (P = .041) as well as shorter survival with metastases at 36 months (P = .030); the metastases(36) rates in ezrin(neg/weak), ezrin(moderate), ezrin(intense) are 58.3%, 25.0%, and 18.4%, respectively. In univariate survival analysis, dichotomized (negative/weak versus moderate/strong) ezrin expression significantly predicted both the 5-year disease specific survival (P = .035) and 5-year metastases (P = .018) but lost this predictive power in multivariate (Cox) analysis. High ezrin expression was also related to high E-cadherin (cytoplasmic) expression, DNA aneuploidy, and high thymidylate synthase expression (P = .046, P = .042, P = .046, respectively). These results suggest that ezrin may play a role in colorectal cancer progression and that ezrin expression might provide clinically valuable information in predicting the biological behavior of colorectal cancer.
Human pathology 09/2008; 39(12):1737-43. · 3.03 Impact Factor
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ABSTRACT: To investigate the changing pattern of alpha-catenin expression and its relationship to clinical and pathological features of colorectal cancer (CRC) patients.
Archival tumor samples were analyzed using immunohistochemistry (IHC) for alpha-catenin in 91 patients with advanced CRC.
The values of alpha-catenin membrane index (MI) and cytoplasmic index (CI) were significantly related to the depth of tumor invasion (P = 0.027, P = 0.020, respectively), high indices being associated with increased depth of the primary tumor invasion (T3 and T4). Similarly, patients with high alpha-catenin expression had a significantly increased risk of lymph node metastasis (32/39 vs 37/52 for MI and 37/45 vs 32/46 for CI) (P = 0.001, P = 0.0001, respectively, for LNN status). An altered expression (i.e., cytoplasmic pattern) was also related (P = 0.047) to the response to chemotherapy; patients with low CI were more responsive (CR: 7/46) than patients with high CI values (CR: 0/45). There was a marginal effect on survival in patients time with metastases (SWM) (P = 0.087); patients with low CI showing slightly longer SWM, but no such effect on disease free survival (DFS) or disease specific survival (DSS). As to co-expression with another member of the adhesion complex (beta-catenin), high alpha-catenin/beta-catenin MI index was of marginal significance in predicting longer DSS (P = 0.063, log-rank).
The results implicate that high alpha-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in CRC.
World Journal of Gastroenterology 09/2008; 14(31):4903-8. · 2.47 Impact Factor
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ABSTRACT: To investigate the changing pattern of beta-catenin expression and its prognostic value in advanced colorectal cancer (CRC).
Archival tumor samples were analyzed for beta-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC.
Membranous beta-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a significant predictor of disease free survival (DFS) (P = 0.023; n = 35), with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045, ANOVA). The other indices were not significant predictors of DFS, and none of the three tested indices (for membranous, cytoplasmic, or nuclear expression) predicted disease-specific survival (DSS). However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046).
Nuclear beta-catenin expression provides additional information in predicting patient outcome in advanced CRC.
World Journal of Gastroenterology 07/2008; 14(24):3866-71. · 2.47 Impact Factor
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ABSTRACT: Thymidylate synthase (TS) is the rate-limiting enzyme in the synthesis of pyrimidine nucleotides and as such a critical target for fluoropyrimidines, which are widely used in the treatment of colorectal cancer (CRC). The purpose of this study was to investigate TS expression in the primary tumours (PTs) and their metastases (M) in advanced CRC.
TS expression was determined immunohistochemically in paraffin-embedded biopsies of PT-M pairs in 39 CRC patients, as related to the clinical data.
There was no difference in the mean TS index of PTs compared with that of M, 1.25 and 1.14, respectively (p=0.12). TS expression of PTs was above the mean more often than that of M (61.5% and 41.0%, respectively, p=0.035). High TS expression in PTs was significantly related to high expression in M (the Fisher exact test, p=0.001). Using the absolute index values, TS expression in PT and M was significantly correlated (Pearson R=0.501, p=0.001). In 29/39 (74.3%) pairs, PT and M had concordant expression levels (Cohen's kappa 0.508, 95% CI 0.260-0.756, p=0.001; intraclass correlation coefficient (ICC) = 0.679, 95% CI 0.358-0.836, p=0.0001). No significant association was found between TS expression and any of the clinicopathological variables, disease outcome (DFS, DSS) or its response to treatment in univariate or multivariate analysis.
Albeit usually higher, TS expression in PT was closely correlated with TS expression in M. This suggests that measurement of TS in primary CRC accurately predicts TS expression in subsequent metastases, which may help in selecting those patients most likely to respond to 5-FU-based regimens.
Scandinavian Journal of Gastroenterology 05/2007; 42(4):471-6. · 2.02 Impact Factor
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ABSTRACT: To investigate the changes that occur in E-cadherin expression during the process of metastasis in colorectal cancer.
E-cadherin expression was detected by immunohistochemistry and two indices of expression were calculated which reflected the level of expression and the locations (membrane and cytoplasm). Univariate and multivariate survival analyses were used to assess the value of these two E-cadherin indices as predictors of both disease-free (DFS) and disease-specific (DSS) survival.
E-cadherin membrane index (MI), but not cytoplasmic index (CI), was significantly higher in primary tumors than their metastases (P = 0.0001). Furthermore, both primary tumor MI and CI were higher among the patients who developed subsequent metastasis (P = 0.022 and P = 0.007, respectively). Interestingly, both indices were higher in liver metastase compared to other anatomic sites (MI, P = 0.034 and CI, P = 0.022). The CI of the primary tumors was a significant predictor of DFS (P = 0.042, univariate analysis), with a strong inverse correlation between CI and DFS (P = 0.006, multivariate analysis). Finally, the MI of primary tumor proved to be a significant independent predictor of DSS, with higher indices being associated with a more favorable outcome (P = 0.016).
Examination of E-cadherin expression and distribution in colorectal tumors can be extremely valuable in predicting disease recurrence. The observation that aberrant cytoplasmic expression of E-cadherin can predict disease recurrence is obviously of great importance for both patients and clinicians, and significantly affects decisions concerning the therapy and management of the patients.
World Journal of Gastroenterology 08/2006; 12(27):4304-9. · 2.47 Impact Factor
