结直肠癌原发灶、门静脉血和肝转移灶K-ras基因突变的研究

目的:观察结直肠癌患者门静脉血液、原发肿瘤组织及相应肝转移灶K-ras基因突变情况,分析三者的一致性,探讨结直肠癌患者门静脉血K-ras基因突变与肝转移关系。方法:实时荧光定量PCR技术和基因测序技术检测59例结直肠癌患者门静脉血液、原发肿瘤组织及15例肝转移灶K-ras基因突变,结合其临床资料分析。结果:59例结直肠癌组织中20例(33.9%)发现K-ras基因突变,18例(30.5%)结直肠癌患者的门静脉血中也发现K-ras基因突变,15例肝转移灶中8例(53.3%)发现K-ras基因突变,与原发癌组织的基因突变率差异不明显(P0.05)。18例门静脉血存在K-ras基因突变者,其相应的肿瘤组织中均发现K-ras突变。结直肠癌组织中无K-ras基因突变者,患者门静脉血未发现基因突变。8例肝转移灶发现K-ras基因突变者门静脉血亦均有K-ras基因突变,7例肝转移灶无K-ras突变者门静脉血也无K-ras突变。原发肿瘤组织、相应门静脉血和5例同时性、2例异时性肝转移灶的K-ras基因突变类型基本一致(即K-ras基因12密码子GGT突变为GAT或GTT),1例异时性肝转移灶K-ras基因突变类型为13密码子GGC突变为GAC。原发癌组织与门静脉血K-ras基因突变一致率为96.6%(57/59),肝转移灶与门静脉血K-ras基因突变情况基本一致,但突变类型有不同。结论:结直肠癌的原发灶、门静脉血及肝转移灶的K-ras基因突变较为一致,原发癌组织和门静脉血均有K-ras基因的突变,预示着肿瘤可能通过血行转移至肝脏。     

结直肠癌原发灶与肝转移灶中KRAS、PIK3CA基因突变的一致性分析

目的探讨结直肠癌原发灶及相应肝转移灶中KRAS、PIK3CA基因突变及临床意义。方法采用实时荧光定量PCR法检测58例结直肠癌原发灶癌组织及相应肝转移灶组织中KRAS、PIK3CA基因突变情况。结果结直肠癌原发灶与肝转移灶中KRAS基因的突变率分别为31.03%(18/58)、25.86%(15/58),最常见的突变位点为G12D;PIK3CA基因的突变率分别为8.62%(5/58)、10.34%(6/58),最常见的突变位点为E545K。有1例同时发生KRAS(G12D)、PIK3CA(E545K)基因突变。结直肠癌原发灶与肝转移灶中KRAS、PIK3CA基因突变的一致性较好。单因素分析显示:KRAS突变与结直肠癌原发灶肿瘤部位、转移灶多少、大体类型相关(P0.05),PIK3CA突变与同时性/异时性肝转移、转移灶多少相关(P0.05)。多因素Cox回归模型显示:同时性/异时性肝转移、KRAS突变状态是影响结直肠癌预后的危险因素。结直肠癌同时性肝转移比异时性肝转移患者的总生存期延长,KRAS野生型比突变型患者总生存期延长(P0.05)。结论结直肠癌中KRAS基因G12D位点突变率最高,原发灶与肝转移灶中KRAS、PIK3CA基因突变一致性较好。原发灶可以作为分子检测的标本来源,基于精准医疗对于靶向治疗的选择,则需再次评估肝转移灶中的基因状态,以达到个体化治疗。     

K-ras基因状态与结直肠癌临床病理特征的关系

目的观察结直肠癌原发灶K-ras基因的突变,探讨其与临床病理特征的关系。方法运用实时荧光定量PCR法检测230例结直肠癌组织K-ras基因12、13密码子的突变,利用χ2检验分析其与临床病理特征的相关性。结果 230例结直肠癌患者中,84例K-ras基因发生突变,突变率为36.5%,其中12密码子突变65例(28.2%)、13密码子突变19例(8.3%)。结直肠癌肺转移患者K-ras基因突变率较无肺转移患者高(P=0.022),12、13单密码子突变与临床病理特征(患者年龄、性别、肿瘤部位、病理分型、TNM分期、Dukes分期、区域淋巴结及肝肺转移)无关(P>0.05)。结论结直肠癌K-ras基因突变可能与肺转移存在相关性,检测K-ras基因突变对结直肠癌患者临床个体化治疗具有指导意义。     

K-ras基因突变在内蒙古地区结直肠癌患者中研究

目的检测内蒙地区结直肠癌K-ras基因突变情况,并结合临床病理资料加以分析。方法提取15例结直肠癌患者结直肠癌手术切除标本组织的DNA,对产物进行基因序列癌组织的DNA聚合酶链反应（PCR）扩增、DNA直接测序分析。结果 K-ras基因突变率为0%,几种分化型的结直肠癌均未发现K-ras基因突变类型,包括12密码子（GGT）、13密码子（GGC）。结论我院结直肠癌患者k-ras基因突变率为0%,转移性结直肠癌患者原发肿瘤与转移灶肿瘤k-ras基因型均相同;结直肠癌患者k-ras基因突变与否与年龄、性别、肿瘤浸润深度、肿瘤组织学类型无关。     

结直肠癌组织中K-ras基因突变的分子病理学检测分析

目的:应用实时荧光定量PCR方法探讨K-ras基因突变情况及其临床病理意义。方法:收集71例结直肠癌石蜡组织,使用实时荧光定量PCR法检测K-ras基因状态。结果:结直肠癌中K-ras基因突变率为35.22%(25/71),发现7种突变(Gly12Asp,Gly12Val,Gly12Cys,Gly12Ser,Gly12Ala,Gly12Arg和Gly13Asp),其中1例为Gly12Val和Gly12Arg双突变,其中56.00%(14/25)的突变发生在第十二密码子的第二位碱基,且最常见类型为Gly12Asp。K-ras基因突变率在男性组中低于女性组(χ2=7.904,P=0.005),在无淋巴结转移组中低于有淋巴结转移组(χ2=5.851,P=0.016),差异有统计学意义,但K-ras基因突变与其他临床病理参数(年龄、肿瘤位置、浸润深度、组织学类型及Dukes’分期)差异均无统计学意义(P>0.05)。结论:女性或有淋巴结转移结直肠癌患者K-ras基因突变多见,可作为筛查是否进行分子靶向治疗的重点人群。     

Anchor Attachment蛋白在结直肠癌中表达增强

目的 探讨Anchor Attachment蛋白（AAP）的表达与结直肠癌浸润、转移的关系及临床意义。方法 免疫组织化学法检测AAP的表达，分析AAP表达水平与肿瘤临床病理特征之间的关系；并用酶联免疫吸附（ELISA）法检测血清中AAP表达水平。结果 结直肠正常肠黏膜、癌原发灶、淋巴结和肝转移灶中AAP的表达阳性率分别为20.5%、53.0%、69.8%和80.0%；癌原发灶、转移淋巴结和肝转移灶中AAP表达阳性率均显著高于正常肠黏膜组织（P＜0.01），转移淋巴结和肝转移灶中AAP阳性率高于癌原发灶（P＜0.05）；淋巴结转移患者和肝转移患者的原发灶AAP阳性率显著高于无转移者（P＜0.01）；Dukes分期A、B、C、D期患者AAP阳性率逐渐增高，各分期之间差异显著（P＜0.01）。83例结直肠癌患者血清AAP水平为(6.3±2.8)μg/L，显著高于30例健康志愿者的(2.2±0.9)μg/L，（t＝6.976，P＜0.01）；Dukes分期A、B期患者血清AAP水平为(5.2±2.6)μg/L，显著低于C、D期患者的(7.1±2.9)μg/L（P＜0.05）。结论 检测外周静脉血AAP水平对预测和判断结直肠癌病情和肝转移有重要意义。     

结直肠癌肿瘤原发灶与肝脏转移灶中PD-L1表达的差异性

目的探讨结直肠癌肿瘤原发灶与肝脏转移灶中PD-L1表达是否一致。方法收集结直肠癌肝转移病例,选取同时行原发灶与肝脏转移灶切除或活检的标本32例。肿瘤原发灶位于直肠7例,乙状结肠12例,降结肠2例,横结肠2例,升结肠9例。肿瘤病理类型:31例管状腺癌,1例黏液腺癌。采用免疫组化法检测结直肠癌原发灶和肝脏转移灶组织中PD-L1的表达。评估整个切片中的肿瘤区域,计数原发灶肿瘤细胞PD-L1阳性细胞百分比,计数原发灶肿瘤浸润免疫细胞PD-L1阳性细胞百分比。采用同样的方法评估转移灶中PD-L1的表达。结果结直肠癌原发灶肿瘤细胞PD-L1阳性率为9. 4%(3/32),原发灶间质免疫细胞的阳性率为21. 9%(7/32);肝脏转移灶瘤细胞PD-L1阳性率为15. 6%(5/32),转移灶间质免疫细胞PD-L1阳性率34. 4%(11/32)。PD-L1在原发灶肿瘤细胞和肿瘤浸润免疫细胞中的表达率均低于其对应转移灶(P=0. 020、0. 037)。结论结直肠癌原发灶和肝脏转移灶的免疫状态存在差别,转移灶可能存在更强的免疫抑制,为临床开展肿瘤免疫治疗提供一定的参考。     

新疆汉族及维吾尔族结直肠癌原发灶与转移灶中KRAS基因突变分析

目的观察新疆地区汉族、维吾尔族人群中结直肠癌(colorectal cancer,CRC)原发灶与转移灶中KRAS基因状态的差异及其与CRC患者临床病理特征之间的关系。方法收集2012年~2014年间新疆地区汉族及维吾尔族CRC标本189例,其中52例有配对转移灶。采用突变扩增阻滞系统(amplification refractory mutation system,ARMS)进行KRAS基因12、13密码子已知常见突变位点检测。结果KRAS基因在CRC原发灶病例中汉族、维吾尔族的突变率分别为42.8%(62/145)、43.2%(19/44),两者差异无显著性(P0.05),T3/T4期及有淋巴结转移的病例中突变率较高(P0.05),但与患者性别、民族、年龄、分化程度、TNM分期、有无远处转移、原发灶所在的部位均无相关性(P0.05)。KRAS基因在CRC转移灶中汉族、维吾尔族的突变率分别为33.3%(12/36)、31.3%(5/16),两者差异无显著性(P0.05),并发现年龄≥65岁者突变率较高(P0.05),与所研究的其他临床病理特征无相关性。52例转移灶中KRAS基因的突变率为32.7%(17/52),而对应的原发灶突变率达50%(26/52),明显高于转移灶(P0.000 1),转移灶突变类型与原发灶一致。结论 KRAS基因在浸润较深、有淋巴结转移及65岁以上发生转移的CRC中突变率较高,在原发灶的突变率高于配对转移灶。KRAS基因突变率在新疆汉族、维吾尔族CRC患者中差异无显著性,提示KRAS基因突变促进CRC的进展,并且在原发灶中更易发生突变,但汉族、维吾尔族间无差异。     

Dact1基因在结直肠癌组织中的表达及其相关性研究

目的：观测Dact1基因在结直肠癌组织的表达及其启动子甲基化状态,并探讨它们之间的关系及在结直肠癌发生中的作用.方法：采用逆转录聚合酶链反应（RT-PCR）检测结直肠癌组织、癌旁组织各50例及正常对照组织20例Dact1基因mRNA的表达情况,甲基化特异性PCR（MSP）检测Dact1基因启动子甲基化状态.结果：结直肠癌组中,9例Dact1基因mRNA失表达（18%）,20例表达低于正常对照组（40%）;癌旁组织组中,1例Dact1基因mRNA失表达（2%）,3例表达低于正常对照组（6%）;正常对照组中,1例Dact1基因mRNA低表达（5%）.Dact1基因在癌组织、癌旁组织、正常对照组织中的甲基化阳性率分别为46%、12%、5%,癌组织组与癌旁组织组及正常对照组阳性率比较,差异均有统计学意义（P＜0.01）,而癌旁组织组和正常对照组阳性率比较,差异无统计学意义（P＞0.05）.Dact1基因mRNA的失表达（低表达）与其启动子甲基化状态的相关性分析有统计学意义（P＜0.05）.结论：Dact1基因mRNA的失表达（低表达）可能参与了结直肠癌的发生发展,其失表达可能与Dact1启动子区甲基化相关.     

K-ras基因突变与结直肠癌生物学行为的关系

目的: 观察结直肠癌组织中k-ras基因突变情况,探讨k-ras基因突变与结直肠癌生物学行为的关系。方法: 采用实时荧光定量PCR法检测123例结直肠癌组织中k-ras基因1号外显子12、13密码子突变情况,结合其临床病理资料分析。结果: 123例结直肠癌组织中k-ras基因突变者53例(40.8%),其中12密码子突变42例(34.1%),13密码子突变者11例(8.9%)。基因突变率与肿瘤大小、肿瘤侵润深度、分化程度无明显相关性,与淋巴结转移、肝脏转移及TNM分期有相关性（P<0.05）。淋巴结转移多者k-ras基因突变率高,有肝脏转移者基因突变率高,TNM分期越晚基因突变率越高。结论: K-ras基因突变可能在结直肠癌的发生、发展中起重要作用,而且与淋巴结转移和肝脏转移有密切相关,可作为判断结直肠癌恶性程度的一个分子生物学指标。     

Organotropism and prognostic marker discordance in distant metastases of breast carcinoma: fact or fiction? A clinicopathologic analysis

Prior studies have suggested that the type of breast cancer influences the location of distant metastases ("organotropism") and that there may be discordance of estrogen receptor and human epidermal growth factor receptor 2 (Her2) expression between primaries and metastases. Our aims were to investigate the relationship between tumor type and metastatic site and to compare biomarker expression between primary and metastatic tumors. We retrospectively reviewed 102 biopsy-proven cases of breast cancer metastatic to distant sites from 2000 to 2010 and 34 corresponding primaries for histologic subtype, grade, lymphovascular invasion, lymph node metastasis, and expression of estrogen receptor and Her2. Most metastases were of ductal (88) and lobular (11) histologic types. Available data on primaries indicated that the majority were grade III with positive lymph node metastasis and lymphovascular invasion. Biomarkers on 73 metastases showed 37 estrogen receptor positive/Her2-, 6 estrogen receptor positive/Her2+, 8 estrogen receptor negative/Her2+, and 22 estrogen receptor negative/Her2-. The most common metastatic sites were the lung (26%), bone (32%), and liver (21%). We found no association between estrogen receptor/Her2 profile and metastatic site (P = .16). When compared with ductal carcinoma, lobular carcinoma showed a unique metastatic pattern to gastrointestinal tract/gynecologic sites (P = .014). Of 34 cases with paired prognostic markers for primary and metastatic sites, 7 (20%) demonstrated discordance in estrogen receptor-positive/Her2 profile between the primary and the metastasis. Because the estrogen receptor-positive/Her2 profile of metastatic breast cancer did not always match that of the primary tumor, it is important to repeat the prognostic markers of metastasis.     

Mutations in K-ras and epidermal growth factor receptor expression in Korean patients with stages III and IV colorectal cancer

K-Ras somatic mutations in advanced colorectal cancer (CRC) can predict resistance to mAbs that target the epidermal growth factor receptor (EGFR). The relationships between K-ras mutations and the EGFR status have not yet been examined, especially in Korean patients. A total of 82 colorectal tumors (stage III-IV) were analyzed. K-Ras mutations at codons 12 and 13 were detected by polymerase chain reaction-single strand conformational polymorphism. The EGFR expressions were examined by immunohistochemistry, and these were graded according to a modified EGFR expression scoring system. The relationships between the patients' characteristics and the survival time and the gene mutation status were analyzed. The EGFR expression was positive in 69 patients (84.1%) and negative in 13 patients (15.9%). The K-ras mutation rate was 35.4%. In all, 20 (68.9%) cases were mutated at codon 12 and 9 (31.1%) cases were mutated at codon 13. No relationship was observed between the EGFR status and K-ras mutation. The median overall survival (OS) was 68.1 months. There was no difference between the K-ras mutant group and the wild type group for overall survival (30.3% vs 21.0%, respectively, at 36 months, P = .777). K-ras mutation and the EGFR status were not independent prognostic factors for OS (P = .105 and P = .499, respectively). For the Korean patients with CRC, the rate of an EGFR protein expression was greater than that for the patients in Western countries, and the rate of K-ras mutations was lower than that for patients in Western countries. This study found no correlation between the EGFR status and K-ras mutations in colorectal tumors.     

Intratumor heterogeneity of K-ras2 mutations in colorectal adenocarcinomas: association with degree of DNA aneuploidy.

Detailed information about intratumor K-ras2 mutations in colorectal adenocarcinomas and a possible association with DNA content heterogeneity is still lacking. DNA diploid and aneuploid subclones, detected among multiple histologically selected primary sectors (57 superficial and 40 deep) and 9 lymph node metastases, were flow cytometrically sorted and separately submitted to codons 12-13 K-ras2 mutation spectrum analysis. DNA aneuploidy was absent among 20 near and 20 distant mucosa sites and present in 7/9 lymph node metastases and in 17/19 primary tumors (90%). Primary intratumor DNA multiclonality was approximately 50%. Degree of DNA aneuploidy (DNA Index) distribution was nonrandom and showed peaks at approximate mean DNA Index values 1.2, 1.5, and 1.8. K-ras2 mutations were detected in 0/20 mucosa cases, in 2/9 lymph node metastases, and in 9/19 adenocarcinomas (47%). No more than one mutation type per tumor was detected. Intratumor distribution of K-ras2 mutations was homogeneous in 6 and heterogeneous in 3 cases. Homogeneous distribution was associated with DNA near-diploid aneuploidy. K-ras2 mutations were strongly associated with DNA Index in the near-diploid region (83%) and almost absent (5%) among DNA near-triploid subclones (P = 0.0001). K-ras2 mutation intratumor heterogeneity indicates that sampling of the tumor may be a critical step and suggests that K-ras2 activation may be a late event in a subgroup of tumors. Our data also suggest the existence of an early process of the colorectal carcinogenesis that favors both K-ras2 mutations and DNA near-diploid aneuploidy. Onset of DNA near-triploid subclones appears, instead, to be independent from K-ras2 activation.     

Less aggressive features of colorectal cancer with liver metastases showing macroscopic intrabiliary extension

We have previously reported the frequent occurrence of bile duct invasion by liver metastases from colorectal cancer. We found that patients with macroscopic intrabiliary cancer growth survive longer after hepatectomy than those without this feature. In the present study, we analyzed the clinicopathological features of primary colorectal cancer showing macroscopic intrabiliary extension of liver metastases. We reviewed 217 patients who underwent initial hepatic resection for colorectal liver metastasis between 1992 and 1998, and analyzed the corresponding primary colorectal cancers clinicopathologically. Microscopic bile duct invasion was found in 89 of 217 cases (40.6%) and, of these cases, 23 (10.6%) had macroscopic intrabiliary extension. Histological sections of the corresponding primary colorectal cancer were available in eight (group A) of these 23 cases. These were compared with 20 cases, selected randomly, of colorectal cancer that did not show bile duct invasion and were diagnosed as liver metastases. These patients underwent hepatectomy during the same period as group A and were used as a control (group B). The histology of the primary tumors revealed well-differentiated adenocarcinoma in 100% of group A and in 25% of group B. The average maximum diameter of the primary tumor was 5.32 cm in group A and 3.61 cm in group B. Venous invasion was detected in 25% of group A and in 90% of group B (P < 0.01), while the incidences of lymphatic vessel invasion and lymph node metastases were similar between the groups. These data suggest that macroscopic intrabiliary extension could be a good indicator of a unique subgroup of colorectal cancers showing less aggressive features even though they develop liver metastases. Careful histological evaluation is important even for metastatic tumors.     

特异引物双扩增即时PCR与传统测序法检测肠癌、肺癌患者K-ras基因突变的比较

目的 以特异引物双扩增即时PCR技术K-ras检测试剂盒(下称ADx-K-ras即时PCR试剂盒)和Sanger DNA测序法同时检测结直肠癌和肺癌患者K-ras基因,以了解K-ras基因突变频率和突变类型,比较ADx-K-ras即时PCR试剂盒和Sanger DNA测序法用于肿瘤K-ras基因体细胞突变检测的临床价值.方法 收集临床肿瘤病理石蜡切片样品827例,其中肠癌样品583例,肺癌样品244例,提取DNA后,对K-ras基因第12和13密码子进行PCR扩增后,使用ADx-K-ras即时PCR试剂盒进行检测,与此同时,将PCR扩增后的产物进行Sanger DNA测序.两种方法对K-ras基因第12和13密码子的检测结果进一步进行各个突变类型的数目和突变率的统计对比.结果 ADx-K-ras即时PCR试剂盒对827例样品检测都得到了明确的结果,检测成功率为100%,Sanger DNA测序成功检测了677例,成功率为81.9%.583例肠癌样品中ADx-K-ras即时PCR试剂盒检测出突变192例,突变检出率为32.9%,Sanger DNA测序成功的样品533例,检出突变160例,突变检出率为30.0%.244例肺癌样品中ADx-K-ras即时PCR试剂盒检出突变26例,突变检出率为10.7%,Sanger DNA测序成功的样品144例,检出突变12例,突变检出率为8.3%.肠癌中第12密码子第2位的GGT→GAT最常见,占全部突变的35.1%(66/188),其次是第13密码子第2位的GGC→GAC,26.6%(50/188),第12密码子第2位的GGT→GTT,18.6%(35/188),第12密码子第1位的GGT→GCT最少见,1.6%(3/188).肺癌中第12密码子第1位的GGT→GTT最常见,占全部突变的40.9%(9/22),同样第12密码子第1位的GGT→GCT最少见,占全部突变的4.5%(1/22).结论 肠癌中K-ras突变率明显高于肺癌.对于甲醛固定石蜡包埋样品而言,ADx-K-ras即时PCR试剂盒对样品的DNA质量的耐受性较好,检测成功率高于Sanger DNA测序,可替代Sanger DNA测序法成为临床上对肿瘤K-ras基因体细胞突变检测的实用方法.     

Can K-ras codon 12 mutations be used to distinguish benign bile duct proliferations from metastases in the liver? A molecular analysis of 101 liver lesions from 93 patients.

It can be difficult to distinguish benign bile duct proliferations (BDPs) from well-differentiated metastatic peripancreatic adenocarcinomas on histological grounds alone. Most peripancreatic carcinomas harbor activating point mutations in codon 12 of the K-ras oncogene, suggesting that K-ras mutational status may provide a molecular basis for distinguishing BDPs from liver metastases. The ability of tests for mutations in codon 12 of K-ras to make this distinction was examined in a two-part study. In the first part we determined the K-ras mutational status of 56 liver lesions and 48 primary peripancreatic adenocarcinomas obtained from 48 patients. In the second part of this study an additional 45 liver lesions were studied. In the first 48 patients, activating point mutations in codon 12 of K-ras were detected in 28 (61%) of the 46 primary carcinomas, in 8 (100%) of 8 liver metastases, in 2 (6.5%) of 31 BDPs, and in none (0%) of 14 liver granulomas. Three BDPs and two primary carcinomas did not amplify. To further estimate the prevalence of K-ras mutations in BDPs we analyzed an additional series of 45 mostly incidental BDPs for K-ras mutations. Three (6.7%) of these 45 harbored K-ras mutations. These results suggest that K-ras mutations may be useful in distinguishing BDPs from metastases in the liver; however, there is some overlap in the mutational spectra of BDPs and pancreatic carcinomas.     

Dynamics of cancer cell subpopulations in primary and metastatic colorectal tumors

Intratumor heterogeneity—heterogeneity of cancer cells within a single tumor—is considered one of the most problematic factors of treatment. Genetic heterogeneity, such as in somatic mutations and chromosome aberrations, is a common characteristic of human solid tumors and is probably the basis of biological heterogeneity. Using mutations in APC, TP53 and KRAS as markers to identify distinct colorectal cancer subpopulations, we analyzed a total of 42 primary colorectal cancer tissues and six paired liver metastases with multipoint microsampling, which enabled analysis of mutation patterns and allelic imbalances with a resolution of 0.01 mm² (about 200 cells). There was usually more than one subpopulation in each primary tumor. Only two of 15 (13.3%) cases with three gene mutations and eight of 27 (29.6%) cases with two gene mutations had a single subpopulation. Cells with mutations in all of the examined genes usually constituted the major population. Multipoint microsampling of six primary and metastatic tumor pairs revealed that the majority of discrepancies in mutation patterns found with the bulk tissue analysis were due to loss of subpopulations in the metastatic tissues. In addition, multipoint microsampling uncovered substantial changes in subpopulations that were not detected with bulk tissue analysis. Specifically, the proportion of KRAS mutation-negative subpopulations increased in the metastatic tumors of four cases. Because KRAS mutation status is linked to cetuximab/panitumumab efficacy, subpopulation dynamics could lead to differences in response to cetuximab/panitumumab in primary versus metastatic tumors.     

K-ras mutations are correlated to lymph node metastasis and tumor stage, but not to the growth pattern of colon carcinoma

In colorectal carcinoma, pathological assessment of tumors is essential for determining therapy and prognosis of the disease. Molecular associations of tumor complexity index and genetic alternations can be helpful to understand the tumor progression mechanism. Oncogenic K-ras is one of the major colorectal cancer associated genes, and is mutated in up to 50% of colorectal cancers. In this current study, we correlated tumor complexity index with mutations in K-ras codon 12, 13, and 61 in association with different clinicopathological parameters such as TNM stage, localization, sex, and age. Formalin-fixed paraffin embedded tissue blocks from colon cancer samples was selected from 88 patients diagnosed with adenocarcinoma. Mutations in the K-ras gene were detected using pyrosequencing technique. Tumor complexity index was calculated using immunohistochemically stained images of the tumor outline of the specimens and then analyzing these pictures using Photoshop CS, Fovea Pro, and Image J computer programs. Statistical analysis was performed with SPSS. K-ras mutations were detected in 17 (19.3%) colon cancer samples. Most of the samples were at a lower complexity index. No correlation was observed between K-ras mutations and complexity index. However, K-ras mutations were correlated with regional lymph node metastasis and tumor stages and complexity index with tumor wall penetration. In conclusion, complexity index and K-ras mutations are independent events; however, both correlate with tumor progression and are important in the biologic development of colon carcinoma.     

西妥昔单抗联合FOLFIRI方案—线治疗转移性结直肠癌的疗效观察

目的：探讨西妥昔单抗（cetuximab）联合FOLFIRI一线治疗转移性结直肠癌（metastatic colorectal cancer,mCRC）的近期疗效及不良反应。方法：回顾性分析33例经组织病理学证实的K-Ras野生型mCRC患者的临床资料,其中观察组17例,一线予以西妥昔单抗联合FOLFIRI化疗方案;对照组16例,只采用FOLFIRI方案化疗。结果：两组患者的一般情况无明显差异（P〉0.05）。观察组和对照组的客观缓解率分别为70.6%和31.4%（P〈0.05）,观察组明显高于对照组;疾病控制率分别为88.2%和81.3%（P〉0.05）,无明显统计学差异。观察组9例（58.8%）患者出现痤疮样皮疹,较对照组（12.5%）明显增多（P〈0.05）;此外包括肝损害、腹泻、白细胞减少、血小板减少等不良反应两组的发生率均无统计学差异（P〉0.05）。结论：西妥昔单抗联合FOLFIRI方案一线治疗K-Ras野生型mCRC近期疗效显著,不良反应可以耐受。