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High frequency of concomitant nm23-H1 and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas

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Abstract

This study evaluated the added significance of nm23-H1 to that of E-cadherin in determining metastatic proclivity in primary sporadic colorectal carcinomas (SCRCs). A clinical cohort of 52 SCRCs was examined for the significance of nm23-H1 and E-cadherin mRNA levels and E-cadherin protein expression levels into the progression of colorectal tumor invasion, determined by their relevance compared with conventional biological markers. A more than twofold decreased expression of nm23-H1 mRNA was reported in 28/52 (54%) of the carcinomas and was positively associated with the presence of nodal metastases and Astler-Coller stages B1 and B2 in 29% and 35% of the SCRCs, respectively. Reduced expression of E-cadherin mRNA was reported in 38.5% of the carcinomas and was similarly associated with stages Astler-Coller B1 and B2 in 27% of the SCRCs. Decreased E-cadherin immunohistochemical expression (grades II and III) was observed in 67% of the samples. E-cadherin mRNA and protein expression were significantly related to each other. The nm23-H1 (+)/E-cadherin (+) coexpression profile was observed in 31% and was significantly related to the absence of lymph node metastases in 31% and stages Astler-Coller B1 and B2 in 29% of the carcinomas examined. Furthermore, the nm23-H1 (−)/E-cadherin (+) coexpression profile was coupled to decreased E-cadherin immunohistochemical protein detection (grade II) in 21% of the cases examined. These findings suggest that impairment of nm23-H1 expression is an early event into the progression of colorectal metastasis that precedes E-cadherin transcriptional silencing in the majority of SCRCs examined. Nm23-H1 may therefore play an important role in suppressing the early steps of metastasis in sporadic cases of colorectal carcinomas.

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Abbreviations

Ab :

Antibody

IHC :

Immunohistochemistry

PCR :

Polymerase chain reaction

RT :

Reverse transcription

SCRC :

Sporadic colorectal carcinoma

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Author notes

  1. George A. Garinis & George P. Patrinos

    Present address: Erasmus University Rotterdam, Faculty of Medicine, MGC-Department of Cell Biology and Genetics, Rotterdam, The Netherlands

Authors and Affiliations

  1. Nursing Military Academy, Laboratory of Research, Athens, Greece

    George A. Garinis, George P. Patrinos & Panayiotis G. Menounos

  2. University of Athens, School of Nursing, Department of Anatomy and Histology, Athens, Greece

    Evangelos N. Manolis

  3. Nikaia Hospital, Department of Surgery, Athens, Greece

    Nick E. Spanakis & George Peros

  4. MGC-Department of Cell Biology and Genetics, Erasmus University Rotterdam, P.O. Box 1738, Dr. Molenwaterplein 50, 3000DR, Rotterdam, The Netherlands

    George A. Garinis

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  1. George A. Garinis
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  2. Evangelos N. Manolis
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  4. George P. Patrinos
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  6. Panayiotis G. Menounos
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Correspondence to George A. Garinis.

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Garinis, G.A., Manolis, E.N., Spanakis, N.E. et al. High frequency of concomitant nm23-H1 and E-cadherin transcriptional inactivation in primary non-inheriting colorectal carcinomas. J Mol Med 81, 256–263 (2003). https://doi.org/10.1007/s00109-003-0420-4

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  • DOI: https://doi.org/10.1007/s00109-003-0420-4

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