On multivariable analyses patients with ERCC1 positive tumors had significantly better disease-free survival (HR 0.70, p = 0.028) and cancer specific survival (HR 0.70, p = 0.032) than those with ERCC1 negative tumors.
We investigated the associations between tumor location, KRAS and BRAF mutation status, and the messenger RNA (mRNA) expression of proteins involved in major signaling pathways, including tumor growth (epidermal growth factor receptor (EGFR)), angiogenesis (vascular endothelial growth factor receptor 2 (VEGFR2)), DNA repair (excision repair cross complement group 1 (ERCC1)) and fluoropyrimidine metabolism (thymidylate synthase (TS)).
Patients with negative expression of ERCC1 in tumor tissues had a significantly longer median DFS and median OS compared to patients with positive expression of ERCC1 (median DFS, 18 vs 10 months, P = 0.006; median OS, 30 vs 17 months, P = 0.012).
Polymorphisms in ERCC1, XPD, and XRCC1 were examined for (a) association with the clinical outcome of 107 non-small cell lung cancer patients receiving front-line platinum-based chemotherapy, and (b) correlation with the ERCC1 mRNA levels of 176 chemo-naive primary tumors.
We observed no correlation between initial ERCC1 level or ERCC1 decrease and overall survival, but we demonstrated correlations between decrease in ERCC1 expression and histologic subtypes of tumors and gender.
We used the tumor tissue samples for an immunohistochemical evaluation of eight biomarkers: ERCC1, BRCA1, p53, p27kip1, class III β-tubulin (TUBB3), Bax, Fas, and FasL.
ERCC1 mRNA levels were higher in metastatic adenocarcinoma NSCLC; TUBB3 mRNA levels were significantly higher in poorly differentiated tumors and in advanced stage NSCLC, which indicates the poor prognosis.
NSCLC specimens that harboring EGFR-activating mutations are more likely to express low ERCC1 and high TUBB3 mRNA levels, whereas tumors from patients with NSCLC harboring KRAS mutation are more likely to express high ERCC1 mRNA levels.
Tumor blocks from these patients were then used in a gold standard analysis to determine individual laboratory sensitivity and specificity for ERCC1 results.Results.
Immunohistochemical analysis revealed that ERCC1 protein expression was not associated with clinicopathological factors, whereas a significantly higher BRCA1 positive rate was found in poorly differentiated tumors (P=0.02).
A set of 6 molecular markers including KRAS, BRAF, and PI3K mutations and expression of topoisomerase-1 (Topo-1), ERCC-1, and thymidylate synthase (TS) using immunohistochemistry were performed in a tumor biopsy.
This study aims to assess the role of polymorphisms in DNA repair genes, excision repair cross-complementation group 1 (ERCC1) and methyl-methanesulfonate sensitivity 19 (MMS19), in tumor response to platinum-based chemotherapy and survival in advanced epithelial ovarian cancer (EOC).
ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.
The significant tumor type (P=0.045), differentiation (P=0.021), p53 (P=0.000) or ERCC1 (P=0.033) positivity dependent differences of SUVmax values were observed.
Furthermore, tumors with EML4-ALK fusions had significantly higher levels of ERCC1, a molecule with a key role in platinum drug efficacy, than tumors without EML4-ALK fusions.
Collectively, these data suggest that there is a synergistic relationship between PARP inhibition and low ERCC1 expression in NSCLC that could be exploited for novel therapeutic approaches in lung cancer therapy based on tumorERCC1 expression.