الفهرس | Only 14 pages are availabe for public view |
Abstract This study aimed to : This retrospective study was performed on 75 cases of colorectal NMA and 75 cases of MA, during the period (Jan. 2007- Dec. 2011), using three manually constructed TMA blocks. TMA is now considered a very effective high throughput technique for testing and validating molecular targets in cancers. MA represents a distinct entity of CRC with more than 50% extra or intracellular mucin content. The importance of this distinct subtype lies in the observed differences between MA and NMA with regard to clinicopathological characteristics, distinct genetic profiles, and pathogenic pathways. In Egypt, the incidence of MA is 22%; nearly double that of worldwide incidence (10-15%). MA is significantly associated with worse survival, younger age of presentation, more depth of invasion, more LN metastasis, less microscopic abscess formation and less peri-tumoral lymphocytic infiltrate than NMA. Mucinous histology is an independent poor prognostic factor. Among several factors, only distant metastasis and presentation with recurrent disease are independent prognostic factors within MA patients. A major focus of CRC research is the assessment of molecular markers that can be potentially useful in determining the cause of the poor prognosis of MA entity. These molecular criteria are also used to define a higher-risk group of CRC patients who may benefit from adjuvant conventional chemotherapy, or new treatments such as anti-EGFR targeted regimens, which are already in clinical use. Despite the discordant results, EGFR and E-cadherin are two of the most studied proteins involved in CRC promotion, progression and treatment. EGFR and E-cadherin positivity rates are significantly interrelated in both NMA and MA groups, with significantly lower rates of expression in MA than NMA. So, targeted therapies against EGFR and E-cadherin aren’t expected to be useful in patients with MA. Moreover, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival in NMA and MA. In NMA cases, high EGFR expression is associated with old age, male gender, multiplicity of tumors, lack of mucinous component and association with schistosomiasis. However, in MA group, high EGFR expression is associated only with old age and with CC subtype. So, targeting EGFR could be useful in old men with NMA associated with bilharziasis. On the other hand, high E-cadherin expression in MA cases is associated with old age, fungating tumor configuration, CC subtype and negative intra-tumoral lymphocytic response. However, in NMA cases, none of these factors is statistically significant. Further molecular studies and clinical trials are needed to explore the relationship between EGFR overexpression and bilharziasis and to introduce more efficient therapies tailored to colorectal MA patients which is necessary to improve their overall survival. |