结肠黑变病与癌基因表达的关系及其临床意义

Relation between melanosis coli and expression of oncogene as well as its clinical significance

目的研究结肠黑变病(MC)黏膜组织大肠癌相关癌基因(APC、Bcl-2、K-ras、Ki-67)和环氧化酶2(Cox-2)表达的变化,与结肠癌、癌前病变之间的比较,探讨MC病变癌变的风险。方法本研究纳入445例患者,根据肠镜检查和病理结果分为5组。MC组108例,对照组分为4组:溃疡性结肠炎(UC)组69例,大肠息肉(CP)组122例,大肠癌(CRC)组96例,正常黏膜组50例。均行黏膜组织相关癌基因(APC、Bcl-2、K-ras、Ki-67)和Cox-2的免疫组化检测。结果 Bcl、K-ras阳性表达率,MC老年组51.4%(36/70)、41.4%(29/70)显著高于MC中青年组26.3%(10/38)、21.1%(8/38)(P<0.05)。APC阳性表达率,MC组63.0%(68/108)、UC组46.4%(32/69)、CP组45.9%(56/122)和CRC组25.0%(24/96)均低于正常黏膜组74.0%(37/50)(P<0.05),CRC组又低于MC组和CP组(P<0.05);Bcl-2、K-ras阳性表达率,MC组42.6%(46/108)、34.3%(37/108)、UC组56.5%(39/69)、62.3%(43/69)、CP组68.9%(84/122)、63.1%(77/122)和CRC组82.3%(79/96)、66.7%(64/96)高于正常黏膜组18.0%(9/50)、8.0%(4/50),UC组、CP组和CRC组又高于MC组(P<0.05);Ki-67阳性表达率,UC组58.0%(40/69)、CP组67.2%(82/122)和CRC组67.7%(65/96)高于MC组33.3%(36/108)和正常黏膜组14.0%(7/50)(P<0.05);Cox-2的阳性表达率,CP组26.2%(32/122)和CRC组36.5%(35/96)高于正常黏膜组8.0%(4/50)(P<0.05);APC、Bcl-2、K-ras、Ki-67、Cox-2的阳性表达率,MC组服用泻药60.7%(54/89)、41.6%(37/89)、33.7%(30/89)、32.6%(29/89)、19.1%(17/89)与未服用泻药者73.7%(14/19)、47.4%(9/19)、36.8%(7/19)、36.8%(7/19)、21.1%(4/19)间差异无统计学意义(P>0.05)。结论 MC老年病人与中青年相比,细胞黏膜凋亡与突变相关性大;MC与正常黏膜、UC、CP比较,MC细胞黏膜凋亡与突变可能性介于正常黏膜与癌前病变之间。为此,临床应重视MC,尤其MC伴息肉,通过肠镜下活检行黏膜组织大肠癌相关癌基因监测,可提高基层医院早期大肠癌的诊治水平,可作为切实可行的MC防治策略。

Objective To study the rules of the expression of oncogene APC,Bcl-2,K-ras,Ki-67 and Cox-2 and their roles in the course of occurrence and development in melanosis coli （MC） and eolorectal carcinoma and its precancerous lesion,and to explore MC relation to assess their risks of cancer. Methods All of 445 patients selected by eolonoscopy, histopathology and special staining confirmed were divided into five groups. Immunohistochemistry method was used to examine the expression of APC, Bcl-2, K-ras, Ki-67 and Cox-2 in MC 108 cases, ulcerative colitis （UC） 69 cases, colorectal polyps（CP） 122 cases, colorectal carcinoma（CRC） 96 cases and 50 subjects of normal colorectal mucosa. Results The positive expression rate of Bel-2 ,K-ras of the older MC group 51.4%（36/70） ,41.4% （29/70） was significantly higher than that of young and middle-aged MC group 26.3 % （10/38）, 21.1% （8/38）（ P G 0.05）. The positive expression rate of APC in the MC group 63.0% （68/108）,UC group 46.4% （32/69）,CP group 45.9%（56/122） and CRC group 25.0% （24/96） was significantly lower than that of normal group 74.0% （37/50） respectively（ P 〈0.05）. The expression of APC of CRC group was significantly lower than that of the MC group and CP group （ P 〈0.05）. The positive expression rates of Bcl-2, K-ras in the MC group 42.6 % （46/108）, 34.3 % （37/ 108）,UC group 56.5%（39/69）,62.3%（43/69）,CP group68.9%（84/122）,63.1%（77/122） and CRC group 82.3% （79/96）, 66.7% （64/96） were significantly higher than that of normal mucosa group 18.0% （9/50）, 8.0% （4/50） respectively （ P 〈0.05）. The expression of Bcl-2 and K-ras was significantly higher in UC group, CP group and CRC group than that of the MC group,respectively （ P 〈0.05）. The positive expression rate of Ki-67 in UC group 58.0% （40/69） ,CP group 67.2% （82/122） and CRC group 67.7 % （65/96） was significantly higher than that of the MC group 33.3%（36/108） and normal group 14.0% （7/50） （ P 〈0.05）. The positive expression rate of Cox-2 in CP group 26.2% （32/122） and CRC group 36.5%（35/96） was significantly higher than that of normal group 8.0%（4/50）（ P 〈0.05） . There was no significant difference of the positive expression rate of APC, Bel-2, K-ras, Ki-67 and Cox-2 between the MC group with laxative use 60.7%（54/89）,41.6%0（37/89） ,33.7%（30/89）,32.6%（29/89）,19.1%（17/ 89） and the MC group not with laxative use 73.7%（14/19）,47.4%（9/19）,36.8% （7/19）,36.8%（7/19）,21.1%（4/ 19） （ P 〉0.05）. Conclusion Apoptosis and muta＇tion of cell mucosal are related to elderly patients with MC, the patients with MC compared with those of normal mucosa, ulcerative colitis and colorectal polyps, the cells mucosal apoptosis and mutation of MC are possible between normal mucosa and precancerous lesions. For the patients with MC and polyps,the active colonoseopy,histopathology and immunohistochemical examination should be carried on as early as possible. Periodical follow-up is necessary,the controlling strategies of MC is practical and can improve level of the diagnosis and treatment of early colorectal carcinoma in primary hospital.