Patients with hMLH1 or/and hMSH2-deficient Metastatic Colorectal Cancer Are Associated with Reduced Levels of Vascular Endothelial Growth Factor-1 Expression and Higher Response Rate to Irinotecan-based Regimen.

Abstract

BACKGROUND/AIM:

The benefit of IFL (irinotecan, fluorouracil and leucovorin) regimen for metastatic colorectal cancer patients (mCRCs) with high levels of microsatellite instability (MSI-H) or loss of mismatch repair (dMMR) protein expression, is uncertain. This study investigated the association of tumour MMR-status and VEGF-1 expression with response to first-line IFL regimen in mCRCs.

PATIENTS AND METHODS:

This prospective study analyzed patients diagnosed with mCRC between August 1st, 1998, and August 30th, 2003, at the Turku University Hospital, Finland. All patients received postoperative IFL regimen. Tumour expression of the MMR proteins, hMLH1 and hMSH2, and VEGF-1 expression were assessed by immunohistochemistry (IHC). Tumours with dMMR were those demonstrating loss of MMR protein expression, and tumours with high VEGF-1 expression were those showing moderate or strong cytoplasmic staining. The primary endpoint was the association between tumour hMLH1 or/and hMSH2-deficient and VEGF-1 expression; the relation between tumour MMR-status and IFL response rate was the secondary endpoint.

RESULTS:

Of the 67 mCRCs patients, 29 (43%) were hMLH1 or/and hMSH2-deficient and 15 (22%) were pMMR mCRCs. At diagnosis, patients with hMLH1 or/and hMSH2-deficient tumours expressed lower levels of VEGF-1 compared to pMMR tumour patients (p=0.01). More than half (n=17, 59%) of those with dMMR were chemosensitive to first-line IFL regimen, while just one-fifth (n=3, 20%) of those with pMMR were chemosensitive to the IFL regimen (p=0.045).

CONCLUSION:

Association between MMR-status and VEGF-1 expression predicts clinical outcome in mCRC patients.

• Authors: Riyad Bendardaf, Fatemeh Saheb Sharif-Askari, Narjes Saheb Sharif-Askari, Kari Syrjänen, Seppo Pyrhönen
• Journal: Anticancer research (Anticancer Res) Vol. 38 Issue 11 Pg. 6399-6404 (Nov 2018) ISSN: 1791-7530 [Electronic] Greece
• PMID: 30396964 (Publication Type: Journal Article)
• Copyright: Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• MLH1 protein, human
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• MSH2 protein, human
• MutL Protein Homolog 1
• MutS Homolog 2 Protein
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives, therapeutic use)
• Colorectal Neoplasms (drug therapy, metabolism)
• Female
• Fluorouracil (administration & dosage, therapeutic use)
• Humans
• Leucovorin (administration & dosage, therapeutic use)
• Male
• Middle Aged
• MutL Protein Homolog 1 (deficiency)
• MutS Homolog 2 Protein (deficiency)
• Neoplasm Metastasis
• Prospective Studies
• Survival Analysis
• Treatment Outcome
• Vascular Endothelial Growth Factor A (metabolism)