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贲门癌中肿瘤相关巨噬细胞浸润及其对预后的影响

Invasion of tumor associated macrophages and its influence on the prognosis in cardia carcinoma

摘要目的:探讨贲门癌组织中肿瘤相关巨噬细胞(TAM)与肿瘤侵袭、转移及预后的相关性。方法:收集2014年1月至2015年1月于莆田市第一医院行D2根治术的100例贲门癌患者癌组织及癌旁组织,以CD163标记M2型TAM。制作组织芯片,采用免疫组织化学法检测组织芯片中CD163的表达情况。以所有癌组织CD163阳性细胞计数的中位数为界值,癌组织中CD163阳性细胞均数≥界值的为TAM高浸润者,反之为TAM低浸润者。分析TAM浸润情况与临床病理特征及预后的关系;采用Cox比例风险模型进行多因素生存分析。结果:贲门癌组织中CD163阳性细胞中位数高于癌旁组织[中位数( P25, P75):32个/高倍视野(HP)(16个/HP,46个/HP)比6个/HP(4个/HP,11个/HP)],差异有统计学意义( Z=-35.044, P<0.01)。TAM低浸润(<32个/HP)组48例,高浸润(≥32个/HP)组52例。肿瘤浸润浆膜及浆膜外的TAM高浸润者比例高于浸润黏膜及肌层者[60.9%(39/64)比36.1%(13/36)],淋巴结转移的TAM高浸润者比例高于无淋巴结转移者[61.8%(42/68)比31.3%(10/32)],TNM分期Ⅲ~Ⅳ期的TAM高浸润者比例高于Ⅰ~Ⅱ期者[64.4%(38/59)比34.1%(14/41)],差异均有统计学意义(均 P<0.05)。TAM高浸润组中位总生存时间较低浸润组短[24.00个月(95% CI 17.25~43.50个月)比62.00个月(95% CI 34.00~68.00个月)],两组总生存差异有统计学意义( χ2=18.137, P<0.01)。淋巴结转移( HR=0.301,95% CI 0.105~0.862, P=0.025)、TNM分期( HR=8.404,95% CI 2.810~25.133, P<0.01)及癌组织TAM浸润水平( HR=4.277,95% CI 2.372~7.712, P<0.01)为患者总生存独立影响因素。 结论:贲门癌中TAM可能在肿瘤侵袭、转移中发挥重要作用,其可能作为预测贲门癌生物学行为及预后的独立指标。

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abstractsObjective:To explore the association of tumor associated macrophages (TAM) with tumor invasiveness, metastasis and prognosis in cardia carcinoma tissues.Methods:The cancer tissues and pericarcinomatous tissues of 100 patients with cardia carcinoma who underwent D2 radical operation in the First Hospital of Putian City from January 2014 to January 2015 were collected. M2-type TAM was marked with CD163. The tissue microarray was made and the expression of CD163 in microarray tissues was detected by using immunohistochemistry. The median number of CD163 positive cells in all cancer tissues was taken as the cut-off value. The patients with the mean number of CD163 positive cells ≥ the cut-off value were those with high TAM infiltration, and vice versa. The association of TAM infiltration with clinicopathological features and prognosis was analyzed, and Cox proportional hazards model was used for multivariate analysis of survival.Results:The positive cell median number of CD163 in cardia carcinoma tissues was higher than that in adjacent tissues [the median number ( P25, P75): 32/high power field (HP) (16/HP, 46/HP) vs. 6/HP (4/HP, 11/HP)], and the difference was statistically significant ( Z = -35.044, P < 0.01). There were 48 cases in low invasive group (< 32/HP) and 52 cases in high invasive group (≥32/HP). The proportion of patients with high TAM infiltration in serosa and extraserosa was higher than that in mucosa and muscle [60.9% (39/64) vs. 36.1% (13/36)], and the proportion of patients with high TAM infiltration for patients with lymph node metastasis was higher than that for patients without lymph node metastasis [61.8% (42/68) vs. 31.3% (10/32)], and the proportion of patients with high TAM infiltration for those with TNM stage Ⅲ-Ⅳ was higher than that for those with TNM stage Ⅰ-Ⅱ [64.4% (38/59) vs. 34.1% (14/41)], and the differences were statistically significant (all P < 0.05). The median overall survival time of high TAM group was shorter than that of low TAM group [24.00 months (95% CI 17.25-43.50 months) vs. 62.00 months (95% CI 34.00-68.00)], and the difference in overall survival was statistically significant (χ 2 = 18.137, P < 0.01). Lymph node metastasis ( HR = 0.301, 95% CI 0.105-0.862, P = 0.025), TNM staging ( HR = 8.404, 95% CI 2.810-25.133, P < 0.01) and TAM infiltration level in cancer tissues ( HR = 4.277, 95% CI 2.372-7.712, P < 0.01) were independent influencing factors for overall survival of patients. Conclusions:TAM plays an important role in the invasion and metastasis of cardia carcinoma and can be used as an independent predictor of biological behavior and prognosis in cardia carcinoma.

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