BACKGROUND: Colorectal cancer (CRC) is a common cancer that in 25-30% of cases develops recurrence in the absence of positive regional lymph nodes. CRC is the second leading cause of cancer-related deaths in the USA. According to the AJCC the 5-year survival ranges from 90% and 50% according to the stage (I vs. III). Thus, the presence of lymph node metastases represents an important prognostic factor. The standard H&E stain nodal evaluations are inadequate for the detection of micrometastasis, especially when sentinel node technique is performed and intraoperative frozen section examination is required. It has been shown that multilevel sectioning and cytokeratin immunohistochemistry (CK-IHC) may improve sensitivity, showing the presence of micrometastases (2 mm or less) in 20-25% of patients with negative H&E routine stain. Molecular markers detected using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) based on mRNA marker detection allows rapid detection of occult micrometastases both in bone marrow aspirates and lymph nodes. We hypothesized that patients initially defined as N0 had nodal occult micrometastasis, which can be revealed by CK-IHC or tumor mRNA marker hepatocyte growth factor receptor (c-MET) overexpression. PATIENTS & METHODS: During postoperative follow-up, 11 patients (8 males, 3 females, median age 59 years) who had undergone colectomy and sentinel node mapping for CRC developed disease recurrence. Intraoperative sentinel node (SLN) evaluation was negative. SLNs were examined using CK-IHC and RT-PCR assay was done to assess the presence of c-MET mRNA. RESULTS: CK-IHC was positive in 6 SLNs and negative in 5, while c-MET detected micrometastases in 10 SLN out of 11 (chi-square= 3.35, OR=12.0, 95%CI 1.11-128.8, p=0.03). CONCLUSIONS: Both CK-IHC and RT-PCR assay to assess c-MET mRNA reveal micrometastases in SNLs from patients with CRC, and may help to identify patients at risk of recurrence.
Occult nodal micrometastases revealed by the mRNA C-MET and its significance in patients with recurrent colorectal cancer.
LUMACHI, FRANCO;
2013
Abstract
BACKGROUND: Colorectal cancer (CRC) is a common cancer that in 25-30% of cases develops recurrence in the absence of positive regional lymph nodes. CRC is the second leading cause of cancer-related deaths in the USA. According to the AJCC the 5-year survival ranges from 90% and 50% according to the stage (I vs. III). Thus, the presence of lymph node metastases represents an important prognostic factor. The standard H&E stain nodal evaluations are inadequate for the detection of micrometastasis, especially when sentinel node technique is performed and intraoperative frozen section examination is required. It has been shown that multilevel sectioning and cytokeratin immunohistochemistry (CK-IHC) may improve sensitivity, showing the presence of micrometastases (2 mm or less) in 20-25% of patients with negative H&E routine stain. Molecular markers detected using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) based on mRNA marker detection allows rapid detection of occult micrometastases both in bone marrow aspirates and lymph nodes. We hypothesized that patients initially defined as N0 had nodal occult micrometastasis, which can be revealed by CK-IHC or tumor mRNA marker hepatocyte growth factor receptor (c-MET) overexpression. PATIENTS & METHODS: During postoperative follow-up, 11 patients (8 males, 3 females, median age 59 years) who had undergone colectomy and sentinel node mapping for CRC developed disease recurrence. Intraoperative sentinel node (SLN) evaluation was negative. SLNs were examined using CK-IHC and RT-PCR assay was done to assess the presence of c-MET mRNA. RESULTS: CK-IHC was positive in 6 SLNs and negative in 5, while c-MET detected micrometastases in 10 SLN out of 11 (chi-square= 3.35, OR=12.0, 95%CI 1.11-128.8, p=0.03). CONCLUSIONS: Both CK-IHC and RT-PCR assay to assess c-MET mRNA reveal micrometastases in SNLs from patients with CRC, and may help to identify patients at risk of recurrence.
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