Despite being a liver tumor with increasing frequency in several countries, cholangiocarcinoma still has a very poor prognosis, especially as it is diagnosed in advanced stages. Considering the challenges in the management of CCA, we carried out this retrospective study in the search to elucidate EGFR expression and amplification profile. Our series represents patients with CCA located in the various segments of the biliary tree with different histological subtypes.
Malignant neoplasms such as CCA may present with EGFR overexpression, amplification and structural changes. Several studies indicate that EGFR is a promising target in the treatment in different types of cancer, being overexpressed in tumors such as lung, head & neck and bladder. Strategies developed to prevent EGFR activation, such as inhibition of receptor binding, or blocking tyrosine kinase activity appear to have potential beneficial in treatment [16-17].
Characterizing the pattern of EGFR expression and amplification in the different histological types of this neoplasm can be very useful in clinical practice. EGFR expression and amplification has been reported only in a few cohorts [18-23].
Our study revealed that EGFR protein expression investigated by IHQ was very frequent in all histological subtypes (80,2%), whereas amplification is only present in a small but important number of cases (10,5%). There were no significant differences in the distribution of IHQ reactivity (p= 0,934) and EGFR amplification (p=0,885) among the histological subtypes, although 4 of 5 cases were detected in DL subtype. Unhappily there was no statistical correlation between EGFR immunohistochemical expression and gene amplification (p=0,136).
In the studies conducted by Shafizadeh [18], Yang [19] and Jung [20] the IHQ expression of EGFR was detected in 80%, 24.5% and 11,9% respectively, and the amplification was 2,7%, 2.3%, 4,7%. In the studies of Yoshikawa [21] and Harder [22] the IHQ expression of EGFR was 22.8% and 60.7%. Peraldo-Neia [23] obtained 51,4% of amplified EGFR cases. Such results are heterogeneous and this can probably be explained by the different case characteristics and methodologies adopted as there is no guideline for evaluating EGFR immunohistochemistry in CCA, making difficult to standardize the results.
In previous studies, as in ours, EGFR amplification was present at a low frequency, except for Peraldo-Neia23 results. None of the studies have made the relationship between the EGFR results with the different histological subtypes, as we did, all the authors classifying CCA based on the affected biliary tree topography.
In general, EGFR amplification in CC seems to be a rarer phenomenon when compared to expression status, data observed in all studies that used the same study design. EGFR expression or amplification was not related to topography, nor to other anatomopathological variables studied in the aforementioned studies. We did not find a relationship between EGFR immunohistochemical expression and amplification, unlike Yang [19] and Jung [20].
The level of IHQ expression of EGFR in the tumor cell membrane is high in all histological subtypes of CCA. EGFR amplification occurred in a small but important portion of the DL and CLC subtypes. There was no clear correlation between the IHQ expression pattern of the protein and gene amplification and we believe that selected cases should be tested directly using FISH.