How does EGFR overexpression affect the development and treatment of rectal cancer?

Abstract

Epidermal growth factor (EGF) stimulates the proliferation of many different types of cells and plays an important role in the formation and growth of tumours. The interaction of EGF with cells is possible by the EGF receptor (EGFR) anchored in the cell membrane. Excess EGFR expression is found in approximately 25-82% of colorectal cancer cases. Attachment of EGF to EGFR results in a conformational change in the receptor, an increase in affinity for neighbouring receptors, receptor dimerisation, and activation of tyrosine kinase in the intraplasmic domain. Activation of EGFR leads to the initiation of the signal transduction pathway to the cell nucleus, via a number of proteins with enzymatic activity-secondary messengers, including KRAS and BRAF proteins. The assessment of the presence of mutations in the KRAS gene has become a standard element in the qualification of patients with advanced colorectal cancer for therapy with the use of monoclonal antibodies. Streszczenie Naskórkowy czynnik wzrostu (EGF) stymuluje proliferację wielu różnych typów komórek i odgrywa ważną rolę w po wstawaniu i rozwoju nowotworów. Oddziaływanie EGF z komórkami jest możliwe dzięki receptorowi EGF (EGFR) zako twiczonemu w błonie komórkowej. Nadmierna ekspresja EGFR występuje w ok. 25-82% przypadków raka jelita grubego. Przyłączenie EGF do EGFR powoduje konformacyjną zmianę receptora, wzrost powinowactwa do sąsiednich receptorów, dimeryzację receptora i aktywację kinazy tyrozynowej w domenie wewnątrzplazmatycznej. Aktywacja EGFR prowadzi do inicjacji szlaku transdukcji sygnału do jądra komórkowego za pośrednictwem wielu białek o aktywności enzymatycz nej-wtórnych przekaźników, w tym białek KRAS i BRAF. Ocena obecności mutacji w genie KRAS stała się standardowym elementem kwalifikacji pacjentów z zaawansowanym rakiem jelita grubego do leczenia z zastosowaniem przeciwciał mono klonalnych.

Five-year follow-up study of stage I-IV rectal cancer including EGFR immunoexpression and p21 immunoactivity

“…The multivariate analysis also showed that high EGFR intensity increases the risk of cancer recurrence 4.3 times (HR = 4.3). Interestingly, our study showed that among patients with high EGFR levels, patients with pT4 predominated ( p = 0.0003), although some researchers say that the correlation between EGFR overexpression and clinical-pathological parameters is not important [ 28 , 30 , 31 ]. According to them, this may seem only an additional molecular event that worsens the result.…”

“…Studies to date have not explicitly confirmed the relationship between the EGFR expression and the survival of patients with rectal cancer [26], although the study by Mayer et al showed that the EGFR expression in more than 50% of cancer cells is a negative prognostic factor [27]. Moreover, overexpression of EGFR (upregulation) is associated with more aggressive tumor growth, a poorer prognosis and higher resistance to radiation; therefore it can potentially be a useful marker in predicting complete responses [25,28,29]. The results obtained in our studies confirmed the above-mentioned reportsthe probability of survival was higher in patients with a low EGFR intensity, p = 0.0004.…”

“…Based on the results of clinical observations, EGFR expression was found to be an adverse prognostic factor. The EGFR blocked by the monoclonal antibody entails the inhibition of many biological signaling pathways, often worsening the result [ 28 , 31 ].…”

P21 is not a prognostic marker for rectal cancer – five-year follow up study of rectal cancer in stages I–IV

“…In the evaluation of p21 clinical value, accumulation of this protein in the nucleus is usually described qualitatively, and its presence in tumorous cells was between 36% and 71%, and even up to 80% of the cases. Such discrepancies in the results can be explained mostly by the heterogeneity of clinical material, different methods of determination, and even material archiving [19][20][21][22][23][24]. The most popular method is applied to p21 reaction in relation to its intensity on the intensity scale (4-5 scale).…”

A five-year follow up study of stage I-IV of rectal cancer with an emphasis on epidermal growth factor over-expression

“…Although rectal cancer is often mosaic and heterogeneous, we currently have a wide range of tests available, which can be a good way to gain a first insight into the genetic profile [13,14]. An increase in the EGFR expression was observed in tumors of different locations and was usually associated with a poor prognosis, increased risk of relapse and a shorter survival rate [15,16,17]. However, the reports on the effect of the EGFR hyper-expression on survival in rectal cancer are conclusive.…”