The Correlation of KRAS Gene Expression and P53 Immunoexpression In Colorectal Adenocarcinoma

Abstract

BACKGROUND: Colorectal Adenocarcinoma (ADCCR) is the third most cancer not only in the world but also in Indonesia. There were 623 cases of ADCCR at Dr Hasan Sadikin hospital within 2015-2017. Both KRAS and TP53 mutation are known as genes which involve in carcinogenesis through the same pathway, namely the chromosomal instability pathway. In West Java, researches focusing on mutation KRAS and p53 also a correlation between both biomarkers among ADCCR patients are still limited. AIM: Therefore, this research aimed to perceive a correlation between KRAS gene expression with p53 immunoexpression in ADCCR.METHODS: Cross section research design was performed to 62 cases of ADCCR as paraffin block taken from 4 hospitals in West Java, including Dr Hasan Sadikin hospital Bandung, Santosa hospital Bandung, Borromeus hospital Bandung and Syamsudin hospital Sukabumi from January 1st 2014 to 31s November 2018. KRAS mutation gene data taken from secondary data at molecular laboratory in Ciptomangunkusumo Hospital Jakarta and Dr Sardjito Hospital Jogjakarta, while the detection of p53 immunoexpression data using immunohistochemical staining was carried out in the Laboratorium of Anatomical Pathology of Padjadjaran University (Dr Hasan Sadikin Hospital). All data were analysed using Chi-Square test with p-value < 0,05 of significant level then proceeded with Stata ver.11 for windows.RESULTS: The results of this study showed that KRAS gene expressions from 62 sample consist of 39 wild type KRAS (62.39%) and 23 mutant KRAS (37.1%). The p53 immunoexpression consists of 27 negative cases (non-mutant p53) and 35 mutant p53, which includes 10 cases as focal expression (16.33%) and 25 cases as diffuse expressions (40.33%). There is a significant association between KRAS gene expression and p53 immunoexpressions in ADCCR (p = 0.04), with mild positive correlation (Rho 0.28). CONCLUSION: This study concluded that KRAS and p53 mutations are involved in carcinogenesis, and the p53 mutation is a more dominant risk factor than KRAS mutation among West Java people. P53 mutations with diffuse pattern tend to express mutant KRAS while p53 negative and having a focal pattern tend to express wt KRAS.

Effect of TP53 deficiency and KRAS signaling on the bioenergetics of colon cancer cells in response to different substrates: A single cell study

“…Studies on CRC patients have found that co-mutations of both TP53 and KRAS were rare, suggesting alternate pathways for them in the development of CRC (Smith et al, 2002). Conversely, other reports detected co-existing mutations in 26 out of 140 patients (Tortola et al, 1999), and more recently 26% of 229 patients presented mutations of both KRAS and TP53 (Chow et al, 2016) and a mild correlation was observed between the expression of the KRAS gene and TP53 immunoexpression in colorectal adenocarcinoma (Rachmawati et al, 2019).…”

Hubungan Tingkat Pengetahuan tentang Diabetes Melitus dengan Persepsi Pencegahan Komplikasi Polineuropati Diabetik

“…Faktor risiko DM yaitu faktor yang dapat diubah (obesitas, pola hidup dan pola makan, stres) dan faktor yang tidak dapat diubah (riwayat keluarga DM usia, jenis kelamin). 2 Hiperglikemia atau peningkatan gula darah adalah efek umum dari DM yang tidak terkontrol,menyebabkan orang DM dapat mengalami perubahan atau kerusakan jangka panjang struktur dan fungsi organ tubuh lain akibat komplikasi yaitu: polineuropati, retinopati, nefropati, penyakit jantung koroner, stroke, dan penyakit arteri perifer. 3 Kasus polineuropati diabetik (PND) merupakan komplikasi terbanyak dari DM tipe 2 dengan gangguan fungsi saraf perifer yang terjadi akibat penyebab utama hiperglikemia yang diawali oleh resistensi insulin pada DM tipe 2.…”

Diagnosis of molecular subtypes of colorectal cancer using immunohistochemistry

“…Увеличение экспрессии TP53 прямо коррелирует с увеличением пролиферативных и инвазивных признаков опухоли. Кроме того, TP53 часто сверхэкспрессируется при дисплазии эпителия крипт, вызванной язвенным колитом [36,37].…”

“…Приобретение соматических мутаций в этом гене может снизить показатели выживаемости при лекарственно устойчивых колоректальных опухолях, которые также содержат мутации KRAS. Маркер имеет цитоплазматическое и мембранозное окрашивание [37,40].…”