The Clinicopathological Correlation of KRAS Mutation and PTEN Expression Status in Primary and Metastatic Colorectal Carcinoma

Redir T Hassan; Bashar Al Hassawi; Maysoon Alkazzaz

doi:10.7759/cureus.53884

The Clinicopathological Correlation of KRAS Mutation and PTEN Expression Status in Primary and Metastatic Colorectal Carcinoma

Cureus. 2024 Feb 8;16(2):e53884. doi: 10.7759/cureus.53884. eCollection 2024 Feb.

Authors

Redir T Hassan¹, Bashar Al Hassawi², Maysoon Alkazzaz³

Affiliations

¹ Department of Anatomy, University of Duhok, Duhok, IRQ.
² Department of Biology, University of Duhok, Duhok, IRQ.
³ Department of Anatomy, University of Mosul, Mosul, IRQ.

Abstract

Background: Colorectal cancer (CRC) research has identified a consistent loss of PTEN expression in both primary tumors and metastasis, highlighting its potential role in this disease. However, the impact of PTEN on downstream proteins of KRAS mutation, namely p-AKT, p-ERK, and p65 (NFkB), remains unknown. This study aims to explore the inhibitory effect of PTEN on KRAS downstream proteins and its correlation with pathological features in CRC patients.

Methods: From January 1, 2015, to December 31, 2021, 86 CRC cases were collected from governmental and private laboratories in the Duhok province. Formalin-fixed, paraffin-embedded tissue blocks were obtained, and the study involved histopathological analysis, immunohistochemistry of PTEN, AKT, ERK, and P65 markers, and molecular analysis of the KRAS gene.

Results: Among the 86 cases, there were 46 males (53.5%) and 40 females (46.5%), with an equal distribution between right colon and left colon/rectum. Tumors larger than 5cm were observed in 47 cases, predominantly displaying a polypoid or ulcerated growth pattern. Most cases were moderately differentiated adenocarcinomas, with stages II and III being the most prevalent 31 cases (36%) and 34 cases (39.5%) respectively. Significant associations were found between PTEN, ERK expressions, and tumor location in the right colon (P=0.031 and P=0.009 respectively). Tumor size correlated with P65 expression (P=0.042). KRAS mutation showed a positive relationship with the type of tumor growth (P=0.035). Tumor grade increased with KRAS mutations (P=0.043). PTEN expression correlated significantly with ERK and AKT markers (P=0.018 and 0.035 respectively). P65 exhibited an association with KRAS mutation (P=0.034).

Conclusion: The study revealed PTEN expression in association with the inhibition of AKT and ERK, and the absence of KRAS gene mutation. Conversely, PTEN is not expressed with the positively reactive P65 and the presence of KRAS mutation. This study contributes valuable insights into the complex interplay between PTEN expression, KRAS mutation, and downstream signaling pathways in CRC. It suggests potential avenues for further research and therapeutic strategies in the context of CRC treatment.

Keywords: colorectal cancer; kras; p-akt and p65; p-erk; pten.