A positive association was found between ERCC1 and XPB expression (r=0.53, p<0.0001) and between TAL2 and EGF expression (r=0.817, p<0.0001) suggesting the existence of gene linkage in these tumors.
The existence of a significant correlation between blood and tumour tissue expression of some genes of clinical interest, such as ERCC1 in NSCLC and HNSCC, could allow the introduction in clinical practice of a simple test that would measure mRNA levels of DNA repair genes in peripheral blood samples instead of tissue samples to determine prognostic and predictive factors in NSCLC and HNSCC patients.
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-expressing circulating tumor cells as a potential diagnostic tool for monitoring response to platinum-based chemotherapy and for predicting post-therapeutic outcome of ovarian cancer.
Among patients with completely resected transitional cell carcinoma of the bladder, those with ERCC1-negative tumors seemed to benefit more from adjuvant gemcitabine plus cisplatin chemotherapy than those with ERCC1-positive tumors.
ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction (PCR-LDR) method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available.
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.
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.
This retrospective study indicates that immunostaining for ERCC1 and class III beta-tubulin may be useful for predicting survival in NSCLC patients receiving carboplatin and paclitaxel against recurrent tumors after curative resection and can provide information critical for planning personalized chemotherapy.
Patients with completely resected non-small-cell lung cancer and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors do not.
Specific mutations in the epidermal growth factor receptor (EGFR) gene as predictors of response to EGFR tyrosine kinase inhibitors (erlotinib, gefitinib) is the first example of markers which predict response to targeted agents.Actual drug targets [e.g. thymidilate synthase (TS) - pemetrexed] or markers of the tumour's ability to repair cytotoxic drug-induced damage [e.g. excision repair cross-complementation group 1 (ERCC1) - cisplatin] may well also complement NSCLC diagnosis.
The CA-125 response rate was 94.5% (52/55) in patients with ERCC1-negative tumors compared to 80% (36/45) in patients with ERCC1-positive tumors (P = 0.026, chi(2)).
However, with reliable methods, established cut-off values and validation in large, prospective, randomized trials, ERCC1 may possibly prove to play an important role as a tumor marker in individualized treatment for upper gastrointestinal cancer.
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)).
On this basis, a retrospective study of mRNA expression of BRCA1 (breast cancer susceptibility 1 gene), XPG (Xeroderma pigmentosum group G gene) and ERCC1 (excision-repair cross complementing group 1 gene) in tumour samples from sarcoma patients treated with trabectedin was conducted, to correlate DNA repair profiles with patient outcome.
A prospective phase II clinical trial in patients with locally advanced non-small-cell lung cancer was conducted with pretreatment tumor collection for determination of RRM1 and ERCC1 expression by real-time reverse transcriptase polymerase chain reaction.
ERCC1 codon 118 polymorphism is a predictive factor for the tumor response to oxaliplatin/5-fluorouracil combination chemotherapy in patients with advanced colorectal cancer.
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).
The results of the present study suggest that ERCC1 expression is an important prognostic indicator for NSCLC, particularly for patients with stage II-III tumors who receive systematic platinum-based adjuvant chemotherapy.