Epidermal growth factor receptor in colorectal carcinoma: correlation with clinico-pathological prognostic factors.

OBJECTIVE: This study was undertaken to determine the relationship between epidermal growth factor receptor (EGFR) status in primary colorectal cancer (CRC) to different clinico-pathological prognostic factors. METHOD: Seventy-nine primary CRC were studied using four scoring systems: 1- EGFR pharmDx score, 2- score modified from the Hercept test [J Histo cytochem, 52 (2004) 893], 3- two additive scores with different cutoff points [Mod Pathol, 11 (1998) 155], 4- two multiplicative scores with different cutoff points [Ann Oncol, 16 (2005) 102]. RESULTS: More than 10% membranous EGFR reactivity was identified in 46.8% (37/79) of the tumours. The intensity was classified as mild, moderate and strong representing 8.9%, 20.3% and 17.7% respectively. Strong correlation was found between the EGFR pharmDx and the proposed scores, at different cutoff points (P < 0.01). A strong correlation was found between EGFR expression, advanced clinical stage (P < 0.01), nodal involvement (P < 0.01) and lympho-vascular invasion (LV) (P < 0.05) in category I factors, poorly differentiated tumours in IIA (P < 0.05), infiltrative border configuration in IIB (P < 0.01), perineural invasion (PN) in III (P < 0.01), and larger tumours in IV (P < 0.01). Heterogenous staining was present in 46.3% of tumours and was associated with an increased score, LV and PN invasion and advanced clinical stage (P < 0.05). CONCLUSION: Using a cut-off point of 10%, similar results with different scoring systems were obtained, representing standardization for EGFR interpretation. EGFR expression is correlated with conventional clinico-pathological prognostic factors.

p53 immunohistochemical expression of Egyptian cervical carcinoma.

Data concerning the expression of p53 in cervical carcinoma, one of the leading cause of death in developing countries, are still confusing. This study was designed to identify p53 in Egyptian cervical carcinoma in an attempt to evaluate its prognostic significance. Eleven chronic cervicitis and 38 invasive carcinoma (31 squamous cell carcinoma (sqcc) and 7 adenocarcinoma, ranging from stage IB to IVB), were stained with the monoclonal antibody anti p53, DO7, using the microwave for antigen retrieval. No immunoreactivity was detected in chronic cervicitis, while nuclear p53 reactivity was detected in all carcinoma and in squamous intra-epithelial lesions (SIL) overlying 8 sqcc. P53 immunohistochemical (IHC) expression was more pronounced in early clinical stages (p=0.007) and in adenocarcinoma compared to sqcc (p=0.015). A positive correlation was present between p53 and heat shock protein 70 (hsp70) expressions (p=0.005). No correlation could be found between p53 expression and tumor infiltrating lymphocytes, the presence or absence of either schistosomiasis or HPV infections. It can be concluded, that in the Egyptian population, p53 immunoreactivity appears to be an early event in cervical neoplasm, and seems to play an important role together with other cell regulatory proteins in the process of carcinogenesis, which could be different between sqcc and adenocarcinoma.

Expression of heat shock protein 70 and c-myc in cervical carcinoma.

Heat shock protein 70 (hsp70), is a molecular chaperone that binds to c-myc and regulates its accumulation and localisation. In an attempt to confirm this association and to find out its prognostic significance in cervical carcinoma, paraffin embedded sections from 15 chronic cervicitis, 31 squamous cell carcinomas (scc) and 7 adenocarcinomas of the uterine cervix were immunohistochemically (IHC) stained for hsp70 and c-myc. hsp70 was faintly expressed cytoplasmically in non neoplastic squamous and endocervical epithelium, while mainly nuclear staining with variable intensities was seen in all scc and in squamous intraepithelial lesions (SIL) overlying 8 tumors. Both cytoplasmic and nuclear staining was noted in adenocarcinoma. c-myc was moderately expressed in the cytoplasm of all non neoplastic endocervical glands, while very mild cytoplasmic staining was noted in squamous epithelium. In SIL and in scc the staining intensity increased and was mainly nuclear. For adenocarcinoma, nuclear and cytoplasmic staining with different intensities was noted. There were significant positive correlations between the IHC expression of hsp70 and c-myc (p = 0.0001). In conclusion, our results confirm the co-association of c-myc and hsp70. This co-association might be a mechanism of tumor escape by preventing hsp70 binding to one of its normal target, the MHC class I, and preventing its subsequent expression on the surface of the cancerous cells. Lastly, the nuclear expression of hsp70 might be considered as an indicator of malignant transformation.