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Letter to the Editor |
Pathologic Anatomy Service, "Gaetano Rummo" General Hospital, Via dell’Angelo 1, I-82100, Benevento, Italy
The immunohistochemical expression of the epidermal growth factor receptor (EGFR) on paraffin-embedded tissue samples has been increasingly studied in the last few years, mainly in colon cancer after the introduction of new targeted monoclonal antibodies in antitumor drug therapy.1 Because EGFR activation can promote cell proliferation and survival,2 it is not surprising that EGFR expression in colon cancer has been found to positively correlate with progression and metastatic potential.3–7
We read with great interest the article by Galizia et al.7 because it represents the first attempt of evaluating the EGFR status of colon cancer in a clinicopathologic setting with a multivariate analysis of putative prognostic factors. Their straightforward results prompted us to evaluate the EGFR immunohistochemical expression of colon cancer tissue and to match the results with the lymph node status on surgical samples. For a pilot study, 22 consecutive pT3 N0 M0 (stage IIA) cases were compared with 22 consecutive pT3 N1 M0 (stage IIIB) cases. All 44 subjects (male-female ratio, 2:1; age range, 40–88 years; mean age, 67.5 years; median age, 69 years) had received diagnoses of moderately differentiated adenocarcinoma with at least seven regional lymph nodes histopathologically identifiable according to the standard criteria.8 Neoplasms arising in the rectum and/or submitted to neoadjuvant therapy were not included. The immunohistochemical assay was performed by means of commercially available standardized reagents (EGFR Kit PharmDx DakoCytomation, Glostrup, Denmark). A single section per case was chosen in which the neoplasm showed the deepest level of invasion of the intestinal wall. The immunohistochemical evaluation was performed by one of us (G.F.) who was blinded to the lymph node status of the selected cases. The staining results were measured semiquantitatively on a scale of 0, 1+, 2+, and 3+ according to the criteria described by Chung et al.9
Overall, EGFR positivity was found in 29 cases (65.9%), with a score 1+ in 23 cases and a score 2+ in 6 cases. Out of the 29 EGFR-positive neoplasms, only 12 cases (41.4%) showed lymph node metastases; conversely, nodal metastases were found in 12 (80%) of 15 EGFR-negative cases. Remarkably, a node-positive case with histopathologic evidence of intra-venular neoplastic emboli also proved to be EGFR negative.
The present observation is based on a limited number of cases of colon cancer with no long-term follow up; however, the relationship between EGFR expression and lymph node status, as well as the relationship between EGFR (and vascular endothelial growth factor) expression and survival, has been recently questioned by other investigators,10 thereby questioning the current opinion of EGFR as a (independent?) prognostic indicator of poor survival in patients with colon cancer.2–7 Current data about EGFR as a negative prognostic indicator in colorectal cancer have been gathered under experimental conditions,2,3,5 and some studies lack multivariate analysis of putative prognostic indicators.4,6 The study by Galizia et al.7 is noteworthy because of the multivariate analysis used, but its results must be regarded cautiously because EGFR positivity was found only 35.6% cases. The immunohistochemical expression of EGFR in colon cancers is reported as occurring in a wide range of cases: 25% to 77%.7–11 One possible explanation for such a high variability is the occurrence of false-negative cases due to a bias in the histopathologic sampling. Figure 1
shows a stage IIIB colonic adenocarcinoma with only few EGFR-positive neoplastic glands within the deepest portion of the tumor; another tissue section from the same tumor could exhibit a more widespread EGFR positivity, or even its complete absence.
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