Abnormal Fhit protein expression and high frequency of microsatellite instability in sporadic colorectal cancer
| Autor: | Cinzia Azzoni, Lorena Bottarelli, Giuseppe Caruso, Enrico Donadei, Cesare Bordi, Luigi Roncoroni, Giovanni Bader, Leopoldo Sarli, Nicoletta Campanini, Costi Renato, Tiziana D'Adda, Domenico Iusco, Gabriella Di Cola, Carlo Salvemini, Silvia Pizzi |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Base Pair Mismatch Colorectal cancer Gene Expression Loss of Heterozygosity Biology medicine.disease_cause MLH1 Polymerase Chain Reaction FHIT Proto-Oncogene Proteins medicine Humans neoplasms Adaptor Proteins Signal Transducing Aged Aged 80 and over Nuclear Proteins Microsatellite instability Cancer Middle Aged medicine.disease Immunohistochemistry digestive system diseases Acid Anhydride Hydrolases Neoplasm Proteins DNA-Binding Proteins MutS Homolog 2 Protein Oncology MSH2 Cancer research Female DNA mismatch repair Carrier Proteins Colorectal Neoplasms MutL Protein Homolog 1 Carcinogenesis Microsatellite Repeats |
| Zdroj: | European Journal of Cancer. 40:1581-1588 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2004.02.021 |
| Popis: | The role of Fhit protein in the oncogenesis of colorectal cancer is still in debate. Recent studies have revealed that reduced Fhit protein expression is associated with a deficiency of the mismatch repair protein. One hundred and twenty unselected patients who underwent curative resection for sporadic colorectal cancer in a three-year period were evaluated for microsatellite instability (MSI) using six microsatellite markers, and for the presence of Fhit and mismatch repair (MMR) proteins (Mlh1 and Msh2) by means of immunostaining. The relations between these markers were analysed. Reduced or absent Fhit expression was noted in 18 out of 118 patients. This altered expression was significantly higher in right-sided cancer (P = 0.005), mucinous tumours (P = 0.005) and in poorly differentiated histological types (P = 0.0001). MSI was found in 22 out of 109 patients, more so in right-sided cancer (P = 0.0001), poorly differentiated histology (P = 0.0001), and mucinous tumours (P = 0.0001). No association was found with TNM stage. MSI was present in 66.7% of tumours with altered Fhit expression and in only 10% of tumours with preserved or intermediate Fhit expression (P = 0.0001). Of the tumours with reduced or absent Fhit expression, 72.2% had loss of nuclear Mlh1 or Msh2 expression compared with only 14% of the preserved or intermediate Fhit expression tumours (P = 0.0001). These results support the hypothesis that deficiency in a MMR gene could be a cause of the high frequency of alterations in Fhit expression, and they permit the suggestion that FHIT gene alteration may be part of the genetic pathway involving MSI through which some colorectal cancers arise. |
| Databáze: | OpenAIRE |
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