The Study On The Expression Of Cancer Stem Cell Markers In Colorectal Carcinoma And Its Relevance To Clinical Pathology And The Feasibility Of Preoperative Chemotherapy For Locally Advanced Colorectal Cancer

Part I:The study on the expression of granzyme M, CD56、 CD 133、 CD44 and ALDHl in colorectal carcinoma and the association with clinicalopathological characteristics.Objectives:To study the expression of GZMM, CD133, CD44 and ALDH1 in colorectal carcinoma and its relationship with clinicalopathological characters.Material and methods:Patients with colorectal cancer who received the first treatment in our hospital from January 2005 to December 2014 were screened and followed up till the end of Dec 2015. We selected 48 cases with locally advanced non-metastatic colorectal cancer treated with preoperative chemotherapy,30 cases of T3N0M0 with disease recurrence and 30 cases of T3N0M0 without disease recurrence, and 30 cases with liver metastasis, respectively. The expression of GZMM, CD133, CD44 and ALDHl in colorectal carcmoma, liver metastasis, preoperative biopsy specimen of neoadjuvant chemotherapy,and normal mucosal tissues of 138 cases were detected using immunohistochemical method. Their different expression and the association with clinicopathological parameters were also analyzed.Results:This study confirmed that GZMM was highly expressed in colorectal cancer (P<0.05) compared with normal mucosal tissues. The expression of GZMM in metastases from metastatic patient were significant higher than that of paired primary cancer tissue. Suggesting that GZMM can be used as a biological indicator for drug resistance and metastasis of colorectal cancer. We also found that CD 133, CD44 were highly expressed in colorectal cancer patients with chemotherapy resistance, metastasis and bad prognosis (P<0.05). ALDH1 were as well highly expressed in colorectal cancer patients with chemotherapy resistance and bad prognosis (P<0.05).Conclusions:GZMM and the cancer stem cell markers including CD133, CD44, ALDHl are highly expressed in colorectal carcinoma, which are closely related to the biological behaviors of invasion and metastasis of colorectal carcinoma. So GZMM, CD 133, CD44, ALDH1 may be used as hopeful markers in predicting the metastastic potential of colorectal carcinoma and the prognosis of colorectal cancer.Part Ⅱ:Safety and efficacy analysis of preoperative chemotherapy for locally advanced colorectal cancerObjectives:To evaluate the safety and efficacy of preoperative chemotherapy for locally advanced colorectal cancer.Patients and methods:Between June 2005 and October 2013,48 patients with locally advanced non-metastatic colorectal cancer were treated with 2 to 8 cycles of 5-fluorouracil (5-FU)-based preoperative chemotherapy. Surgery was performed at a median interval of 4 weeks (range 2 to 8 weeks) after chemotherapy. This study was retrospectively reviewed to assess the response, toxicity, and extent of resection.ResultsPreoperative chemotherapy was well tolerated in all patients; grade 3 toxicity was found in 5 patients (10.4%) in the forms of leukopenia, nausea/vomiting and hand-foot syndrome. One patient (2.1%) achieved clinical complete response (cCR) and underwent a "wait and see" approach. Sixteen patients (33.3%) experienced a reduction in tumor size. Radical surgery was performed in 47 patients,42 (87.5%) of whom had microscopically clear resection margins (R0). Three patients underwent palliative resection, whereas another 2 patients were found to be unresectable in an exploratory operation. Post-operative complications were observed in 17.8%(8/45) of patients, with no 30-day mortality. Pathological T down staging was seen in 23 (51.1%) patients, and pathological complete response (pCR) was observed in 2 (4.4%) patients.Conclusions:Preoperative chemotherapy for locally advanced primary colorectal cancer is feasible, with acceptable toxicity and high rates of RO resection, with acceptable morbidity and mortality. Neoadjuvant chemotherapy (NCT) should be considered as an option for treatment to improve the outcomes of radical surgery.