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International Journal of Colorectal Disease

, Volume 22, Issue 2, pp 115–126 | Cite as

Distinct molecular patterns based on proximal and distal sporadic colorectal cancer: arguments for different mechanisms in the tumorigenesis

  • Cinzia Azzoni
  • Lorena Bottarelli
  • Nicoletta Campanini
  • Gabriella Di Cola
  • Giovanni Bader
  • Antonio Mazzeo
  • Carlo Salvemini
  • Silvia Morari
  • Davide Di Mauro
  • Enrico Donadei
  • Luigi Roncoroni
  • Cesare Bordi
  • Leopoldo Sarli
Original Article

Abstract

Background and aims

Colorectal cancer (CRC) ranks as the fourth most frequently diagnosed cancer worldwide. CRCs that arise proximally or distally to the splenic flexure show differences in epidemiologic incidence, morphology, and molecular alterations, suggesting the existence of two categories of CRC based on the site of origin. The aim of the present work is to investigate the histological and molecular differences between CRCs located proximally and distally to the splenic flexure, and their potential involvement in tumor prognosis and therapeutic strategies.

Methods

We evaluated 120 patients affected by sporadic CRC for clinicopathologic features, microsatellite instability (MSI), loss of heterozygosity (LOH) of chromosomes 18q, 8p, and 4p; they were also investigated for hMlh1, hMsh2, Fhit, p27, and Cox-2 immunostaining.

Results

The mucinous histotype was more frequent in the proximal than in the distal CRCs (p<0.004). The frequency of MSI phenotype was higher in proximal than in distal tumors (p<0.001); moreover, reduced or absent hMlh1, Fhit, p27 immunohistochemical expressions were more frequent in proximal than in distal tumors (p<0.001 and 0.01 for p27). In contrast, the frequency of LOH in 18q was higher in distal than in proximal tumors (p=0.002). No significant differences were observed between proximal and distal tumors in the frequency of LOH in 8p and altered expression of hMsh2 and p53 protein.

Conclusion

These different features may reflect different genetic pathways of carcinogenesis and support the hypothesis of a different mechanism of cancer development between the proximal and the distal colon, with potential implications in the therapeutic approach.

Keywords

Colon cancer Proximal colon Distal colon Molecular profile Therapeutic approach 

Notes

Acknowledgement

This work was supported in part by a grant from “ Lega Italiana per la lotta contro i tumori”.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Cinzia Azzoni
    • 2
  • Lorena Bottarelli
    • 2
  • Nicoletta Campanini
    • 2
  • Gabriella Di Cola
    • 3
  • Giovanni Bader
    • 1
  • Antonio Mazzeo
    • 1
  • Carlo Salvemini
    • 1
  • Silvia Morari
    • 1
  • Davide Di Mauro
    • 1
  • Enrico Donadei
    • 1
  • Luigi Roncoroni
    • 1
  • Cesare Bordi
    • 2
  • Leopoldo Sarli
    • 1
  1. 1.Dipartimento di Scienze Chirurgiche, Sezione di Chirurgia Generale e Terapia ChirurgicaUniversità di ParmaParmaItaly
  2. 2.Department of Pathology and Laboratory Medicine, Section of Pathological AnatomyParma University, Medical SchoolParmaItaly
  3. 3.Research Laboratory “Biotech”Parma University, Medical SchoolParmaItaly

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