Refined mapping of loss of heterozygosity on 1q31.1-32.1 in sporadic colorectal carcinoma

AIM: To explore precise deleted regions and screen the candidate tumor suppressor genes related to sporadic colorectal carcinoma. METHODS: Six markers on 1q31.1-32.1 were chosen. These polymorphic microsatellite markers in 83 colorectal cancer patients tumor and normal DNA were analyzed via PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for Loss of heterozygosity (LOH) scanning and analysis. Comparison between LOH frequency and clinicopathological factors was performed by χ2 test. RESULTS: 1q31.1-32.1 exhibited higher LOH frequency in colorectal carcinoma. The average LOH frequency of 1q31.1-32.1 was 23.0%, with the highest frequency of 36.7% (18/49) at D1S2622, and the lowest of 16.4% (11/67) at D1S412, respectively. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622 (1q31.3-32.1). There was no significant association between LOH of each marker on 1q31.1-32.1 and the clinicopathological data (patient sex, age, tumor size, growth pattern or Dukes stage), which indicated that on 1q31.1-32.1, LOH was a common phenomenon in all kinds of sporadic colorectal carcinoma. CONCLUSION: Through our refined deletion mapping,the critical and precise deleted region was located within 2 cM chromosomal segment encompassing 2 loci (D1S413, D1S2622). No significant association was found between LOH and clinicopathologic features in 1q31.1-32.1.

Ezrin expression and its translocation in human primary sporadic colorectal carcinoma and prognostic significance

Objective: The membrane-linking protein Ezrin is highly expressed in several types of human cancers. The cor- relations between its immunoreactivity and histopathological data as well as patient outcome have previously been shown. However, the role played by Ezrin in the carcinogenesis, progression and metastasis of primary sporadic colorectal carcinoma (SCRC) is still under investigation. This study assessed Ezrin protein expression in a series of clinical specimens. Methods: Immunohistochemical analysis was used to characterize patterns of Ezrin expression in 132 cases of SCRC, including 74 metastatic cases and 58 non-metastatic cases and 43 adjacent normal colorectal mucosa. Results: (1) The expression rate of Ezrin in SCRC (79.5%) was significantly higher than in adjacent normal colorectal mucosa (11.6%) (P < 0.001); (2) The total expression rate of Ezrin was 86.5% and 70.7% in metastatic group and non-metastatic group, respectively (P = 0.026); the membrane expression rate of Ezrin was 31.1% and 6.9% in the two groups, respectively (P < 0.01); (3) There was no relation- ship between the expression of Ezrin with age, gender, tumor size, location, degree of differentiation and invasive depth; (4) In the cases with followed-up data, univariate analysis demonstrated that Ezrin expression and its membrane translocation was correlated with worse patient’s disease-free survival (DFS) (Puni < 0.05). Conclusion: Ezrin was expressed in the majority of SCRC and associated with adverse prognostic factors. The increase expression and the switch of Ezrin localization from the cytoplasm to the membrane were closely correlated with metastasis in SCRC. It might be served as an important parameter for determining tumor biological behavior.