Wen-Yih Liang

PURPOSE: The features of T1 colorectal adenocarcinoma and the risk determination of lymph node metastasis were reviewed. Prognostic factors were assessed to verify whether the risk of lymph node metastasis would influence the long-term prognosis. METHODS: Patients undergoing curative resection of T1 colorectal adenocarcinoma at the Taipei Veterans General Hospital from December 1969 to August 2002 were retrospectively studied. Patients with synchronous colorectal cancer, distant metastasis, familiar adenomatous polyposis, or inflammatory bowel disease were excluded. The associations between lymph node metastasis and clinicopathologic variables were evaluated univariately using chi-squared test, Fisher's exact test, or Student's t -test, and multivariately using logistic regression. Univariate analysis by the log-rank test and multivariate analysis by Cox regression hazards model determined the factors influencing the overall survival. RESULTS: A total of 159 patients were included. Sixteen patients (10.1 percent) had lymph node metastasis. The risk of lymph node metastasis included histologic grade (P = 0.005), lymphatic vessel invasion (P = 0.023), inflammation around cancer (P = 0.049), and budding at the invasive front of tumor (P = 0.022). Age (P = 0.001) and number of total sampling lymph nodes (P < 0.0001) were found to be the factors influencing the overall survival. CONCLUSIONS: Variables that predict lymph node metastasis in surgically resected T1 colorectal carcinoma may not impact the long-term prognosis.

The ability of tumor cells to resist apoptosis triggered by immune cells results in their escape from immune surveillance of the host. A critical effector of apoptosis is the Fas/Fas ligand (FasL) system that mediates the tumoricidal effects of cytotoxic T cells. Recently, in vitro cleavage of Fas expressed in various tumor cells by matrix metalloproteinase-7 (MMP-7) was demonstrated. In the present study, we first analyzed the influence of this metalloproteinase on Fas signaling in SW480, HCT-15 and HT-29 colorectal carcinoma (CRC) cells by assessing their responses to either an agonistic Fas antibody (CH11) or the FasL-bearing Jurkat cells after they were pretreated with MMP-7. Interestingly, both antibody- and Jurkat cell-induced apoptosis in three different CRC lines were significantly reduced by MMP-7 pretreatment. Additionally, immunohistochemical (IHC) staining was used to examine the expression levels of MMP-7 and Fas in tumor samples of 54 CRC patients. In agreement with our in vitro observation, the expression of MMP-7 in tumor tissues was inversely correlated with those of Fas (P < 0.001; chi2-test). Moreover, shortened survival was found in patients with a higher MMP-7 and a lower Fas expression, respectively, in their tumor tissues (P < 0.0001). Finally, by multivariate analysis, we discovered that MMP-7 (P = 0.001) and Fas levels (P = 0.036) were independent prognostic factors for CRC patients. These results suggest that Fas downregulation and a consequential increased resistance to FasL-triggered apoptosis resulting from upregulated MMP-7 in colorectal cancer cells could be a key mechanism for their escape from the immune surveillance, thereby predicting a poor survival in CRC patients.

BACKGROUND: To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT). METHODS: Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR). RESULTS: Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%). CONCLUSIONS: In patients with pre-CRT serum CEA ≥6 ng/ml, those with "normalized" CEA levels after CRT may have similar DFS to those with "normal" (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml.