1.The expressions of c-Met, VEGF, EGFR and HER-2 in the AFP-producing gastric cancer
Yu FANG ; Lin WANG ; Guimei LI ; Yu ZHANG ; Ningrong YANG ; Shukui QIN
China Oncology 2016;26(8):662-669
Background and purpose:Alpha fetoprotein (AFP)-producing gastric cancer (AFPGC) is considered to be a special type of gastric cancer. Currently, the effect on AFPGC is not as good as the common AFP-
negative gastric cancer. Therefore, it is very important to explore clinicopathological features of AFPGC cancer, to improve diagnosis and individualized treatment. This study is to investigate the expressions of hepatocyte growth factor receptor c (c-Met), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2) in the AFPGC.Methods:A total number of 44 cases of AFPGC (serum AFP≥10 μg/L) tissues were selected as a test group. There were 30 cases of serum AFP≥200 μg/L. This study collected 30 cases of gastric cancer with normal AFP and 30 cases of hepatocellular carcinoma with increased AFP (serum AFP≥200 μg/L) as 2 control groups. The cases of the 3 groups had the same clinical stage basically. The expressions of c-Met, VEGF, EGFR and HER-2, CD34 were detected by immunohistochemistry (EnVision staining method). Tumor microvessel density (MVD) was calculated by marking CD34, and the results were analyzed. The clinicopathologic parameters were recorded accurately: gender, age, highest level of serum AFP, tumor differentiation, tumor stage, tumor location, lymph node metastasis, liver metastasis, Lauren classiifcation, etc. These patients were followed up regularly. The clinical pathological features of AFPGC patients were investigated.Results:AFPGC clinical characteristics showed that, among 44 cases of AFPGC group, 86.36% (38/44) had lymph node metastasis, 54.55% (24/44) had hepatic metastasis, intestinal type was 36.36% (16/44), diffuse type was 56.82% (25/44), mixed type was 6.82% (3/44). The positive expression rates of c-Met protein in AFPGC, gastric cancer with normal AFP, hepatocellular carcinoma with increased AFP were 73.33% (22/30), 70.00% (21/30) and 53.33% (16/30), respectively. The positive expression rates of VEGF protein were 76.67% (23/30), 56.67% (17/30) and 66.67% (20/30), respectively. The positive expression rates of EGFR protein were 53.33% (16/30), 40.00% (12/30) and 73.33% (22/30), respectively. The “++ and +++” expression rates of HER-2 in AFPGC, gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 38.64% (17/44), 23.33% (7/30) and 26.67% (7/30), respectively. The MVD values in AFPGC, gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 23.03±10.24, 21.92±11.45 and 19.43±7.83, respectively. Compared with gastric cancer with normal AFP, expression of VEGF protein was signiifcantly higher in the AFPGC (P<0.05). Compared with hepatocellular carcinoma with increased AFP, the expression of c-Met protein was significantly higher in AFPGC (P<0.05).Conclusion:AFPGC is prone to lymph node metastasis and hepatic metastasis. The major part is the diffuse type in Lauren classiifcation. The positive expression rates of VEGF protein in AFPGC were signiifcantly higher than the gastric cancer with normal AFP. The positive expression rates of c-Met protein in AFPGC were signiifcantly higher than the hepatocellular carcinoma with AFP increased.
2.Efficacy analysis of crizotinib for brain metastases in ALK-rearrangement-positive non-small cell ;lung cancer
Wei HUANG ; Lin WANG ; Shukui QIN ; Ningrong YANG ; Rong LI ; Chen XUN ; Zhaojun XIA
China Oncology 2015;(6):467-471
Background and purpose: Although crizotinib could manifest marked antitumor activity in anaplastic lymphoma kinase (ALK)-rearrangement-positive non-small cell lung cancer (NSCLC) patients, but brain metastases is always occured in such patients. This study aimed to explore the efifcacy and treatment mode of crizotinib for brain metastases in ALK-rearrangement-positive NSCLC. Methods: The clinical data of 6 patients with brain metastases in ALK-rearrangement-positive NSCLC treated in 81 Hospital of PLA from Jan. 2011 to Aug. 2014 were analyzed retrospectively. Results: Three patients had brain metastases before crizotinib administration, 1 obtained partial response (PR) and 2 obtained stable disease (SD) in intracraninal tumors. The median progression free survival (PFS)for the ifrst period of crizotinib administration were 5.7 months, and the sites of ifrst disease progression were brains. All the 6 patients continued to receive crizotinib after radiotherapy with the median PFS of 4 months. One patient even experienced a median PFS of 23.3 months for the second period of crizotinib administration, and her brain tumors obtained complete response (CR). Conclusion:The data of this study suggest that crizotinib is effective for brain metastases in ALK-rearrangement-positive NSCLC, and continued administration of crizotinib after radiotherapy for isolated intracraninal tumor progression is a elective treatment option for such patients.
3.Mutation of k-ras mutation and evaluation of anti-EGFR monoclonal antibody combined with chemotherapy in Chinese colorectal cancer patients
Lin WANG ; Yingxia CHEN ; Ningrong YANG ; Jun QIAN ; Xiufeng LIU ; Feng WANG ; Chen XUN ; Shukui QIN
Cancer Research and Clinic 2010;22(7):458-460
Objective To observe the k-ras mutation rate of colorectal cancer in China, and assess the effect and toxicity in advanced colorectal cancer (CRC) patients (pts) receiving chemotherapy combined with monoclonal antibody against Epidermal Growth Factor Receptor (EGFR). Methods The k-ras mutation of 139 samples collected from our hospital were tested by pyrophosphoric acid sequencing. Twenty-three advanced colorectal cancer patients were treated with chemotherapy combined with anti-EGFR monoclonal antibody, including 3 initial treated and 20 retreated. In the total 23 patients, 18 were treated with cetuximab and chemotherapy, and S were treated with nimotuzumab and chemotherapy. Cetuximab was taken with 400 mg/m2 first time, and then 250 mg/m2 every week. Nimotuzumab was taken with 400 mg first time, and then 200 mg every week. Eight patients of the total 23 received anti-EGFR monoclonal antibody combined with irinotecan, 12 with FOLFIRI, 3 with FOLFOX4. Results k-ras mutation type (mt) was detected in 39.6 % (55/139) of pts, k-ras wild type (wt) was 60.4 % (94/139). In 22 effect evaluable patients, 5 received PR and 9 SD, and RR and DCR were 22.7 % and 63.6 %, respectively. TTP was 124 days. Thirteen of the 22 patients tested k-ras mutation, of the 11 k-ras mt pts, 4 received PR, 4 SD and 3 PD. Two patients of k-ras mt received PD after 2 cycles treatment. Acneform eruptions were observed in 15 patients of 18 pts who received cetuximab and paronychia in 3 pts. Eruption or paronychia was not observed in all patients who received nimotuzumab. Grade 3 hypersensitivity were occured in 2 patients with cetuximab, and one of them alternated nimotuzumab in next cycle didn't get hypersensitivity any more. Conclusion The mutation rate of k-ras in Chinese colorectal cancer patients was similar with westerners. The effect of cetuximab combined with chemotherapy on advanced colorectal cancer was reliable. Nimotuzumab combined with chemotherapy worth to be studied further because of the promising effect and mild toxicity.