Abstract:
Cancer stem cells (CSCs) play a major role in development, progression and in
aggressive chemo-resistant behavior as they provide a continuous pool for clonal
proliferation of malignant cells. LGR5, one of the most important stem cell marker is
implicated very early in metamorphosis of malignant transformation. LGR5 is directly
involved in cell proliferation through its effects on Wnt- β catenin pathway. In this cross-
sectional study we used 109 formalin fixed paraffin embedded (FFPE) tissue samples
and evaluated immuno-reactive score (IRS) of LGR5 expression in normal colonic
mucosa, adenomas and colorectal cancer tissue samples. Association between LGR5
expression and various clinico-pathological parameters including grade, stage and
lymph-node metastasis was assessed .The comparison of mean LGR5 IRS scores across
non-neoplastic tissue, adenomas, and carcinomas was done . A binary logistic regression
was performed to examine the association of LGR5 expression (high vs. low) with
lesion type, T stage, N stage, and histological grade. Results: Histological type and
tumour grade significantly influence LGR5 expression. Conventional Adenocarcinomas
and well differentiated Grade 1 tumours exhibited strong LGR5 expression followed
by moderately differentiated (Grade 2) tumors, as compared to mucinous and signet ring
cell variants and poorly differentiated tumours Grade 3(p <0.001). There was a
statistically significant difference in mean IRS scores among the three groups (p <
0.001). The highest mean IRS score was observed in adenomas (mean = 9.42 ± 3.06),
followed by carcinomas (6.12 ± 3.62), whereas non-neoplastic tissues exhibited the
lowest mean IRS score (2.15 ± 2.02). The patients with Non-Neoplastic Lesions were
less likely to have high LGR5 expression (OR=0.077, p<0.001) in comparison to
patients with neoplastic lesions. The study identified higher IRS score for LGR5
expression in colorectal cancers and adenoma as compared to normal mucosa, thus
identifying it as a marker of neoplastic transformation. Increased LGR5 expression in
adenomas and grade 1 CRC identified this stem cell marker as a significant diagnostic
marker useful for early neoplastic lesion. Decline of LGR5 expression in poorly
differentiated tumours verified it as a marker of poor prognosis.
