DIFFERENTIAL EXPRESSION OF LGR5 AND ITS DIAGNOSTIC SIGNIFICANCE IN NEOPLASTIC AND NON –NEOPLASTIC COLORECTAL LESIONS

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.