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Gajjar et al. ERCC1 in colorectal cancer

were 47.6%, 39.9% and 12.5%, respectively in Asian correlation found between ERCC1 polymorphism and
[20]
patients, very similar to previous reports in Caucasian ERCC1 protein expression. Similarly, Qi et al. in
populations. [4,13] patients with gastric cancer and Takenaka et al. in
[21]
patients with non-small cell lung cancer also showed
In the present study, it was found that there was positive that ERCC1 genotypes were not correlated with
ERCC1 protein expression in 72% of CRC patients. ERCC1 protein expression. On the other hand, another
Likewise Wang et al. reported 68.1% positive ERCC1 study found increased ERCC1 protein levels in CRC
[14]
immunoreactivity in patients with gastric cancer. patients with the C/T or T/T genotypes. [4]
However, in 2 studies, ERCC1 positivity was observed
in 45% and 55% of patients with colorectal and stage Several studies have investigated the prognostic role
III disease, respectively. [4,15] This discrepancy may be of ERCC1-118 SNP and ERCC1 protein expression
due to several factors including antibody used, scoring in CRC patients and other cancers types but the
technique, used and in preparation of the paraffin results obtained were controversial. In one report
embedded tissue blocks. ERCC1 codon 118 C/C genotype was significantly
associated with higher response rates, progression-
To date, most studies have focused more on pathologic free survival, and OS in metastatic CRC. However,
[4]
and molecular features, but less on clinical features another supported the pharmacogenetic role of the
with molecular variables. Therefore, in the present ERCC1-118 C > T change and emphasized that the
study, correlation of ERCC1 polymorphism and protein T allele was a marker of a better outcome in patients
expression with clinicopathological parameters was with CRC treated with OX-based schemes. [22,23] Thus,
evaluated. However, none of the clinicopathological the relationship between ERCC1 codon 118 SNP
parameters was significantly associated with ERCC1 and clinical outcome in patients with CRC remains
gene polymorphism. Similarly, another study did controversial although one study reported significantly
not find statistically significant correlations between shorter progression-free (P < 0.01) and overall (P <
genotype distributions and gender, tumor location, 0.01) survival in patients having positive ERCC1
tumor invasion, lymph node metastasis, tumor stage, IHC staining in colorectal tumor tissues. It was also
[4]
or histology in CRC patients. The present study observed that 5-year DFS and OS were significantly
[16]
showed no significant association between ERCC1 lower in combined therapy group with positive ERCC1
protein expression and clinicopathological parameters tumors than in the same group patients with negative
apart from tumor site. Still another study reported no ERCC1 tumors. However, in present study, due to
[15]
significant differences in gender, tumor stage, nodal short follow-up period of 15 months, no correlation of
stage, histological differentiation, lympho-vascular RFS and OS was observed with ERCC1 C118T SNP
invasion, neural invasion, or postoperative CEA and ERCC1 protein expression. We recognize that a
levels between the ERCC1 positive and negative limitation of this study is that SNP assessment was not
groups. However, ERCC1 positive expression was confirmed by Sanger sequencing. Further studies will
significantly associated with older age group patients be necessary to validate our findings.
(P = 0.031). Also it has been shown in patients with
[17]
nasopharyngeal carcinoma that the expression level In summary, the current study reveals that ERCC1
of ERCC1 increased significantly with higher T stage protein expression was significantly higher in patients
and clinical stages (P < 0.05). Thus, at least in that with rectal cancer as compared to patients with colon
malignancy, ERCC1 seemed to be a valid biological cancer, which may indicate biological and functional
indicator to predict prognosis. In the present study, differences between the two subsets and may emerge
[18]
ERCC1 positive protein expression was found to be as an important marker for patients with rectal cancer.
significantly higher only in rectal cancer patients as However, further studies with larger sample sizes
compared to colon cancer patients (P = 0.046). and longer follow-up period are necessary for a more
definite conclusion.
In one report the identical ERCC1 C/T polymorphism
at codon 118 was found to influence the level of Financial support and sponsorship
ERCC1 expression. This may be due to that, although This work was financially supported by Gujarat Cancer
both the AAC and AAT codons encode asparagine, Society (GCS)/Gujarat Cancer and Research Institute
the AAT codon usage is significantly reduced, (GCRI) and Directorate of Medical Education and
thereby decreasing ERCC1 translation capability and Research (DMER).
protein level. Therefore, in the present study we
[19]
correlated ERCC1-118 polymorphism and ERCC1 Conflicts of interest
protein expression. However, there was no significant There are no conflicts of interest.
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ December 29, 2016 475