非小细胞肺癌微转移灶的检测及临床意义

非小细胞肺癌(NSCLC)是常见的恶性肿瘤，治疗效果不佳，有许多术中证实淋巴结阴性的患者仍在术后出现复发，这可能是由于存在常规病理手段无法发现的微转移病灶所导致。近年来，免疫组化和分子生物学方法已应用于外周血、骨髓及肿瘤附近淋巴结中微转移灶的检测，但是检测微转移灶的指标选择及临床意义目前仍有争论。作者讨论常见的检测NSCLC微转移的方法及检测结果的临床意义。     

我国南北两家医院贲门癌淋巴结微转移的对比分析

目的探讨贲门癌高、低发病区淋巴结微转移的特点。方法采用免疫组织化学方法,用细胞角蛋白19（CK19）单抗和CD44v6单抗分别检测海南省农垦总医院（低发区组,48例）和河南科技大学第一附属医院（高发区组,45例）贲门癌患者常规病理学检查阴性的淋巴结微转移情况,并结合临床病理资料进行统计学分析。结果共24例（25.81%）47枚（6.99%）淋巴结存在微转移,低、高发区两组淋巴结微转移阳性率的差异有统计学意义（4.33%vs 9.46%,χ2=6.763,P=0.009）,两组的临床重新分期率差异无统计学意义（18.75%vs 33.33%,χ2=2.576,P=0.108）。87例获随访,两组淋巴结微转移阳性者的复发率均明显高于微转移阴性者（P〈0.05）;生存率均明显低于微转移阴性者（P〈0.05）。组间比较,高发区组的复发率低于低发区组（19.05%vs 35.56%,χ2=3.986,P=0.046）。结论不论在贲门癌高、低发病区均有必要监测淋巴结微转移。贲门癌淋巴结微转移阳性者复发和死亡率高。     

肺癌外周血中EGFR mRNA、SP-D mRNA、LUNX mRNA表达的临床意义

目的:应用逆转录聚合酶链反应(RT-PCR)技术检测肺癌患者肿瘤组织和外周血中EGFRmRNA、SP-DmRNA、LUNXmRNA的表达,探讨其作为肺癌微转移检测分子标志物的可行性。方法:应用RT-PCR技术检测40例非小细胞肺癌组织和15例肺良性病变组织中EGFRmRNA、SP-DmRNA、LUNXmRNA的表达;检测40例肺癌患者外周血中靶基因的表达,并以15例良性肺疾病患者和10名健康人外周血作为对照。结果:40例肺癌患者病理组织中EGFRmRNA、SP-DmRNA、LUNXmRNA的表达率为77.5%(31/40)、100%(40/40)、100%(40/40),外周血中EGFRmRNA、SP-DmRNA、LUNXmRNA表达阳性率分别为55.0%(22/40)、52.5%(21/40)和57.5%(23/40);对照组中15例肺良性病变患者病理组织中EGFRmRNA表达率为13.3%(2/15),无SP-DmRNA和LUNXmRNA表达,15例肺良性病变患者和10名健康人的外周血中无EGFRmRNA、SP-DmRNA、LUNXmRNA表达。结论:EGFRmRNA、SP-DmRNA、LUNXmRNA作为检测肺癌组织及肺癌外周血微转移的分子标志物具有良好的敏感度和特异性;三者表达与肺癌TNM分期、组织学类型和癌细胞分化程度关系密切。     

Radiobiological determination of growth kinetics and radiosensitivity of pulmonary micrometastases of the R1H tumour

The aim of the study was to determine the radiosensitivity and the growth kinetics of pulmonary micrometastases of the R1H tumour of the rat. Lung metastases were induced by intravenous injection of viable tumour cells. At different time intervals (3–32 days) after injection, lungs were locally irradiated with 200 kVp X-rays, using 1.5 Gy/fraction. Total doses of 6–33 Gy were administered within 11 days. Endpoints used were survival time, local control rate, and number of metastases in the lungs at autopsy. The data were evaluated using the multi-target model. Beginning in the fifth week after tumour cell inoculation the animals started to exhibit a pronounced dyspnoea and were sacrificed. Sections revealed an extensive metastatic infiltration of the lungs. With increasing total dose a prolongation of survival time as well as an increase in cure rate was observed. The number of metastases found in the lungs decreased with increasing total dose. It is concluded that metastatic growth does not start earlier than 3 days after tumour cell inoculation and accelerates continuously. The doubling time of the tumour cells in the micrometastases decreases continuously and from 5.2 to 1.2 days between day 3 and 40, whereas larger metastases containing more than 10⁶ cells show gompertzian growth kinetics. The cell doubling time in this stage of metastatic growth is longer than 5 days. During the first 4 weeks of metastatic growth the radiosensitivity of metastatic R1H cells in the lungs is the same as in vitro.     

Detection of Breast Cancer micrometastases in peripheral blood using immunomagnetic separation and immunocytochemistry

BACKGROUND: Although there have been many reports on the immunocytochemical detection of bone marrow micrometastases in breast cancer patients, peripheral blood micrometastases (PBM) have rarely been studied by immunocytochemistry (ICC). METHODS: PBM in operable and metastatic breast cancer patients were studied using immunomagnetic separation of tumor cells followed by immunocytochemistry (IMS-ICC). RESULTS: PBM were not detected in any peripheral blood samples from 21 healthy women, six patients with benign disease, or in a 21 patients with primary operable breast cancer, of which there were 7 stage I (n=7), 9 stage II, 2 stage III, and 3 inflammatory tumors. On the other hand, PBM were detected in 8 of 29 patients with metastatic breast cancers (27.6%). The number of tumor cells per patient varied from 2 to 90 cancer cells (median: 8 cells). Positivity of PBM was not significantly associated with the first site of recurrence, number of involved organs, tumor marker status, performance status, or disease-free interval, but it was significantly (p<0.01) associated with progesterone receptor negativity. CONCLUSION: PBM are very rare in primary operable breast cancer patients but can be observed in a considerable number of metastatic breast cancer patients. The clinical significance of PBM still remains to be established.     

Are lymph node micrometastases of any clinical significance in dukes stages A and B colorectal cancer?

PURPOSE: The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer. METHODS: Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1–11; median, 4; rectum, 1–15; median, 3) was examined with use of an anticytokeratin antibody. RESULTS: Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5–67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18–97) months, and for patients without micrometastases, 48 (range, 19–111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases. CONCLUSION: Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.This study was supported by the Swedish Cancer Foundation (Project No 2520-B96-10XCC, Project No 3453-B97-05XBB).Read at the Second Surgical Week, Västerås, Sweden, August 18 to 22, 1997.     

检测非小细胞肺癌患者外周血CK19 mRNA微转移的临床意义

目的检测非小细胞肺癌（NSCLC）患者外周血CK19 mRNA的表达情况,探讨其作为分子标志物检测NSCLC微转移的可行性。方法应用逆转录聚合酶链反应（RT—PCR）技术检测48例NSCLC患者,15例肺良性疾病（BLD）患者和10例健康人外周血CK19 mRNA的表达。结果NSCLC患者CK19 mRNA的阳性表达率明显高于BLD患者和健康对照者,差异有统计学意义（Х^2=24．735,P=0．000）。Ⅰ、Ⅱ、Ⅲ、Ⅳ期NSCLC患者外周血中CK19 mRNA阳性表达率分别为44．4％（8／18）,75．0％（9／12）,92．3％（12／13）,4／5,不同临床分期NSCLC患者外周血CK19 mRNA阳性表达率比较差异有统计学意义（Х^2=8．820,P=0．032）;有无淋巴结转移NSCLC患者外周血CK19 mRNA阳性表达率比较差异亦有统计学意义（Х^2=6．813,P=0．009）;而不同病理类型、不同分化程度NSCLC患者外周血CK19 mRNA阳性表达率比较差异无统计学意义（Х^2=4．655,P=0．459;Х^2=1．204,P=0．548）。结论检测外周血CK19 mRNA表达可作为诊断NSCLC患者微转移的一个有价值的参考指标。     

多株单克隆抗体检测胃癌阴性淋巴结微转移的研究及临床意义

目的:探讨单克隆抗体联检在诊断胃癌阴性淋巴结微转移中的应用价值。方法:选择鼠抗人细胞角蛋白(CK)-19单克隆抗体,鼠抗人上皮膜抗原(EMA)单克隆抗体,鼠抗人癌抗原CA72-4(TAG-72)单克隆抗体采用免疫组化法对65例可切除性胃癌患者的385枚阴性淋巴结进行微转移阳性表达检测,对相关临床病理因素及预后进行统计。结果:三种单克隆抗体联检出17例(26.2%)胃癌的33枚(8.6%)淋巴结有微转移。弥漫型胃癌的淋巴结微转移度(38.9%)明显高于肠型胃癌(10.4%)。淋巴结微转移与肿瘤侵袭胃壁深度有关。有微转移的5年生存率(65.3%)明显低于无转移者(87.4%),预后较差。结论:单克隆抗体联检可以提高胃癌淋巴结微转移检出度,提高临床病理分期准确性,指导术后综合治疗,判断预后。