EGFR, p16INK4a and E-cadherin immuno-histochemistry and EGFR point mutations analyses in invasive cervical cancer specimens from Moroccan women.

The involvement of human papillomavirus in the development of cervical cancer has been firmly established. However, better management of cervical cancer rests on good diagnosis and an effective therapy. In this study we evaluated the frequency of point mutations in epidermal growth factor receptor (EGFR) for future use of tyrosine kinase inhibitors in clinical treatment and to assess the use of EGFR, p16INK4a and E-cadherin as biomarkers in cervical cancer diagnosis with immunohistochemistry. Fifty-three patient specimens of cervical cancer were analysed for HPV infection, for EGFR mutations in exons 18 through 21, and for expression of EGFR, p16INK4a and E-cadherin by immunostaining. Results showed that 79.24% of the cases (42/53) are HPV positive and the HPV types more closely associated with risk are HPV 16 and 18. In all 53 analysed specimens, any mutation affecting the EGFR kinase domain in exons 18 through 21 was observed. Expressions of EGFR, p16INK4a and E-cadherin were detected in 88,67% (47/53), 92,45% (49/53) and 79,24% (42/53) of analysed specimens respectively. Thus, EGFR, p16INK4a and E-cadherin would be excellent tools for IHC analysis during the cervical cancer development. EGFR and p16INK4a can be used for early diagnosis and E-cadherin for cancer progression and cell migration. However, treatment of cervical cancer with TKIs may not be effective and the identification of other EGFR inhibitors is needed.

Identification of G2607A mutation in EGFR gene with a significative rate in Moroccan patients with nasopharyngeal carcinoma.

The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of nasopharyngeal carcinoma (NPC). Sixty Moroccan patient specimens of NPC were analysed for EGFR mutations in the region delimiting exons 18 and 21 by direct sequencing. Our results showed the absence of mutations in the EGFR kinase domain in these exons in all 60 analysed specimens. Sequence analysis of the EGFR—TK domain, revealed the presence of (G2607A) polymorphism at exon 20. The genotypes AA and GA were found respectively in 39 (65%) and 16 (26.6%) cases. Statistical analysis showed no difference between the polymorphism and either gender or age of patients. Mutations in EGFR kinase domain are rare events in NPC biopsies, suggesting, that treatment of NPC patients with TKI may not be effective. However, EGFR G2607A polymorphism at exon 20 is frequent in NPC cases and could be associated to clinical response to TKI therapy.