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.

Abstract

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. 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. 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. 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.