Epidermal growth factor receptor (EGFR) overexpression and microsatellite instability in human colorectal cancer (CRC)?

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EGFR is expressed in 90% of the colorectal tumours. In the experimental models, EGF like peptides have been shown to exert either trophic effect and to control anti tumoral immune response in CRC. The most immunogenic tumours have high frequency of MSI-H. The aim of this work was to analyze EGFR expression in colon tumours with respect to their microsatellite status. Patients and methods. The clinico-biological data of 130 consecutive patients [57 W, 73 M; median age 70 (29 to 100) yrs] were collected. MSI-H was determined using Fluorescent PCR Pentaplex and Immunohistochemistry (IHC) on the basis of at least 3 instable sequences out of 5 monomorphic microsatellite markers, and lack of hMLH1 or hMSH2, respectively, when tumoral tissue was compared to the normal homologous mucosa. EGFR expression was similarly determined via IHC. Only membrane expression of EGFR was evaluated semi quantitatively as E (extension) x I (intensity) with values for each item varying from 0 (negative or absent) to 4 (extended or very strong). The “E x I” score from 0 to 16 was used to define two classes of tumours with weak (Wk<9) or high (ST>or=9) EGFR expression with maximum E x I score being =9 in normal tissues. The statistical analyses were carried out by X2 or Anova and multiple regression logistic tests and survival KM curve construction. Results. The tumours were of stage I (4), II (54), III (49) and IV (23) in pTNM classification with 55 tumours displaying high EGFR expression (ST) on IHC. There was no difference on ST status concerning the type of surgery, pTNM, and tumour size at baseline, the number and the type of adjuvant or palliative chemotherapy afterward. Among 24 tumours with MSI-H out of 130, 2 did not express hMSH2 and 21 hMLH1 on IHC with 16 of them (66%) being ST (vs 36% in tumours MSS; p=0.01) and 6 MSI-H tumours displaying a score of 16. The univariate analysis showed a significant relationship between ST of EGFR, and young age (4838 vs 6226; P=0.01), right localization (58% vs 32% left and 34% rectum; P=0.017), pathology characteristic of tumours (66% vs 45% ulcerated or 26% perforated; P=0.009), the absence of mucoid component (54% vs 34%; P=0.03), and a more important lymphoid infiltration (49% vs 30%; P=0.04) whereas the number of lymph node, vascular or nervous infiltrations were not significantly related. There was no difference in term of survival according to the EGFR expression although the time to relapse was longer (21 month) in patients with tumours (of stage II) with strong expression than for the tumours with weak EGFR expression (19 month; P=0.05). In multivariate analysis only MSI-H status appeared as independent factor (Odds Ratio = 2.7, 95% IC 1.1-7.2; P=0.04). Conclusion: The high EGFR expression in colorectal tumours may be linked to the mismatch repair alteration.