P-0173 - Updates in rare colorectal signet ring cell adenocarcinoma
|Date||28 June 2014|
|Event||World GI 2014|
|Topics|| Colon Cancer
|Presenter||Al-Rahman Foda Abd|
|Citation||Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165|
A. Foda Abd1, A. Abdel-Aziz1, A. El-Hawary1, A. Hosni2, K. Zalata1, A. Gado1
Colorectal mucinous adenocarcinoma, a morphologic subtype of colorectal carcinoma (CRC), has more than 50% of the tumor composed of mucin, either extracellular with mucin lakes (colloid carcinoma) (CC) or intracellular with signet ring cells (signet ring cell adenocarcinoma) (SRA). SRA is a rare entity that accounts for 1% of CRC, with five times more often in Egypt than the rest of the world. SRA has specific clinicopathological features than ordinary adenocarcinoma (OA) and even CC. In this study, we aimed to compare SRA, OA and CC regarding clinicopathological, histological parameters, survival, EGFR (as a marker of proliferation), MMP-13 (as a marker of invasion) and E-cadherin (as a marker of adhesion) expressions.
In this work, we studied tumor tissue specimens from 19 patients with SRA, 47 patients with OA and 56 patients with CC, who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicohistopathological parameters and survival data were revised and analyzed using established statistical methodologies. High density manual tissue microarrays were constructed using modified mechanical pencil tips technique and immunohistochemistry for EGFR, MMP-13 and E-cadherin was done.
In comparison to OA and CC, SRA was significantly associated with younger age (P = 0.002 and 0.046 respectively), more lymph node metastasis (P = 0.002 and 0.034 respectively), advanced stage (P = 0.003 and 0.034 respectively), more lymphovascular emboli (P = 0.018 and 0.028 respectively), perineural invasion (P < 0.001 and 0.001 respectively), less arousal on top of adenoma (P = 0.026 and 0.014 respectively) and worse disease-free and overall survival (P < 0.001 and 0.049 respectively). On the other hand, only OA was significantly associated with more peritumoral lymphocytic infiltrate (P = 0.037) and microscopic abscess formation (P = 0.003) than SRA. SRA expressed EGFR, MMP-13 and E-cadherin in a significantly lower rates than OA (P < 0.001 for all). The same was true with CC for EGFR (P = 0.01) and E-cadherin (P < 0.001), but no significant difference of MMP-13 expression was observed between SRA and CC (P = 0.451). In a univariate analysis, neither EGFR, MMP-13 nor E-cadherin expression showed a significant impact on disease-free or overall survival in patients with SRA.
SRA is a specific entity of CRC that has more aggressive clinipathological features and worse survival than OA and even CC. SRA expressed EGFR, MMP-13 and E-cadherin in a significantly negative/low rates. So, targeted therapies against these biological molecules aren't expected to be useful in patients with SRA. Both SRA and CC expressed MMP-13 in a significantly negative/low rates, emphasizing that mucinous CRCs in general depend on mucin dissection in invasion rather than matrix metalloproteinases secretion. Further studies are needed to explore the molecular characteristics of colorectal SRA to introduce successful tailored targeted therapies for it.