Molecular analysis of Iranian colorectal cancer patients at risk for Lynch syndrome: a new molecular, clinicopathological feature.

PURPOSE: Microsatellite instability (MSI) and mismatch repair (MMR) gene expression present a hallmark mutational signature of Lynch syndrome as a common hereditary cancer predisposing condition. Since there is not enough data of molecular and clinicopathological aspects of the disease in Iranian populations, this article is a new description in Central Iran.

METHODS: It is a descriptive analytical study in which we screened 1659 colorectal cancer (CRC) patients based on early-onset disease and Amsterdam II criteria during 14 years (2000-2013). MSI testing was applied through a commercial kit evaluating five mononucleotide markers (BAT-25, BAT-26, MON0-27, NR-21, and NR-24) using a fluorescent multiplex PCR method. Immunohistochemistry (IHC) staining was set up to detect expression of four mismatch repair (MMR) genes including MLH1, MSH2, MSH6, and PMS2. SPSS 16 software was used to analyze the data.

RESULTS: Overall, 31 of 45 screened at-risk families were eventually included to MSI testing of which 9/31 patients (∼29 %) showed MSI in their tumor tissues including 6 (19.4 %) MSI-H (high). BAT-26 was the most instable marker with instability in 7/31 MSI tumors (22.6 %). IHC-MMR staining was absent in 7/31 probands (22.6 %) of which in 4 cases, both MSH2/MSH6 (57.1 %) and, in 2 cases, both MLH1/PMS2 showed deficiency (28.6 %), and just in one case, MSH6 was defective (14.3 %). IHC-MMR was absent in all 6 MSI-H tumors while none of 3 MSI-L tumors were MMR-deficient. Just single MSH6-defective tumor showed MSS state. The frequency of CRC among MMR-deficient and MMR-proficient families was 67.5 and 27.9 %, respectively. The most common extracolonic cancer among both MMR-deficient and MMR-proficient groups was stomach, respectively, with 26.7 and 16.5 %.

CONCLUSIONS: A different molecular and clinicopathological phenotype of tumors in CRC Iranian patients at risk for Lynch syndrome could suggest some new molecular mechanisms about which more evaluations are necessary.