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乳腺癌的肺转移:原发性和转移性肿瘤的配体组织化学、细胞核及结构分析,重点关注转移发生时间和生存率。

Pulmonary metastases of breast carcinomas: ligandohistochemical, nuclear, and structural analysis of primary and metastatic tumors with emphasis on period of occurrence of metastases and survival.

作者信息

Kayser K, Biechele U, Kayser G, Dienemann H, Andrè S, Bovin N V, Gabius H J

机构信息

Department of Pathology, Thoraxklinik, Heidelberg, Germany.

出版信息

J Surg Oncol. 1998 Nov;69(3):137-46. doi: 10.1002/(sici)1096-9098(199811)69:3<137::aid-jso4>3.0.co;2-l.

DOI:10.1002/(sici)1096-9098(199811)69:3<137::aid-jso4>3.0.co;2-l
PMID:9846499
Abstract

BACKGROUND AND OBJECTIVES

Pulmonary metastases of breast carcinomas have a high frequency and are often subject to surgical intervention. To contribute to advances in the knowledge about morphometric and biochemical parameters of primary tumors and their metastatic lesions, analysis of syntactic structure and thermodynamic aspects as well as of expression of distinct glycohistochemical features with respect to period of metastasis occurrence and patient survival is desirable.

METHODS

Clinical history, surgical findings, histopathological reports, survival of the patients with a maximum follow-up of 15 years, and paraffin blocks of 32 breast carcinoma specimens and their pulmonary metastases were examined. Only potentially curative resections of both the breast carcinoma and their metastases have been included for analysis. The following markers were applied: neoglycoconjugates with histoblood group A- and H-trisaccharides, lactose, alpha-N-acetyl-D-galactosamine and the Forssman disaccharide, a polyclonal immunoglobulin G fraction from human serum with specificity for 9-0-acetylated sialic acid, which is a tumor marker for melanomas, the serum lectins serum amyloid P component and mannan-binding lectin, the mannose-specific plant lectin concanavalin A, and monoclonal antibodies specific for estrogen and progesterone receptors, respectively. In addition, measurements of the integrated optical density (IOD) and tissue structure were performed.

RESULTS

The frequency of expression of hormone receptors and expression of binding capacities to most of the applied probes was similar between the primary and metastatic tumors; however, it varied markedly between different patients. For the IOD parameters, a close association between the primary tumors and their metastases was seen, especially a rather low S-phase-related tumor cell fraction and a high percentage of tumor cells with an IOD >5C. The mean time for the development of intrapulmonary metastases measured 43 months. It was considerably longer in progesterone receptor-negative tumors (49.7 months) and those with a lack of expression of sites with specificity for the Forssman disaccharide (48.7 months). The survival was positively correlated with the presence of binding capacity of histoblood group A-trisaccharide and certain structural parameters, especially the structural entropy and its current. The presence of estrogen and progesterone receptors was not associated with the total survival at a statistically significant level.

CONCLUSIONS

Histochemical features between the primary breast carcinoma and their intrapulmonary metastases can evidently vary. Analysis of the hormone receptor status in metastatic lesions seems to be useful for diagnostic purposes only in rare cases, i.e., distinguishing metastases from primary lung carcinoma. Nonetheless, the survival of patients with metastasizing breast carcinoma is associated with features of the primary tumors, especially the detection of binding capacities for the Forssman disaccharide and the histoblood group A-trisaccharide. Extent of lymph node involvement of the breast carcinoma is not prognostic for later pulmonary involvement.

摘要

背景与目的

乳腺癌肺转移的发生率较高,且常需进行手术干预。为推动对原发性肿瘤及其转移灶的形态计量学和生化参数的认识进展,分析句法结构和热力学方面以及不同糖组化特征在转移发生时间和患者生存方面的表达情况是很有必要的。

方法

对32例乳腺癌标本及其肺转移灶的临床病史、手术发现、组织病理学报告、最长随访15年的患者生存情况以及石蜡块进行了检查。仅纳入了对乳腺癌及其转移灶进行的潜在根治性切除病例进行分析。应用了以下标志物:含组织血型A-和H-三糖、乳糖、α-N-乙酰-D-半乳糖胺和福斯曼二糖的新糖缀合物;对9-O-乙酰化唾液酸具有特异性的人血清多克隆免疫球蛋白G组分,其为黑色素瘤的肿瘤标志物;血清凝集素血清淀粉样P成分和甘露聚糖结合凝集素;甘露糖特异性植物凝集素伴刀豆球蛋白A;以及分别针对雌激素和孕激素受体的单克隆抗体。此外,还进行了积分光密度(IOD)和组织结构的测量。

结果

原发性肿瘤和转移瘤之间激素受体的表达频率以及与大多数应用探针的结合能力表达相似;然而,不同患者之间差异明显。对于IOD参数,原发性肿瘤与其转移灶之间存在密切关联,尤其是S期相关肿瘤细胞比例较低且IOD>5C的肿瘤细胞百分比很高。肺内转移发生的平均时间为43个月。在孕激素受体阴性的肿瘤(49.7个月)和缺乏对福斯曼二糖特异性位点表达的肿瘤(48.7个月)中,这个时间要长得多。生存与组织血型A-三糖的结合能力以及某些结构参数,特别是结构熵及其电流呈正相关。雌激素和孕激素受体的存在与总生存无统计学显著关联。

结论

原发性乳腺癌与其肺内转移灶之间组织化学特征明显不同。转移灶中激素受体状态的分析似乎仅在极少数情况下对诊断有用,即区分转移瘤与原发性肺癌。尽管如此,转移性乳腺癌患者的生存与原发性肿瘤的特征相关,特别是福斯曼二糖和组织血型A-三糖结合能力的检测。乳腺癌的淋巴结受累程度对后续肺受累无预后价值。

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